Patent rights

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Farma Zutical

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Jul 15, 2013, 4:23:08 PM7/15/13
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Before Rare Connect-gate I had the pleasure of ending up in an air plane next to a high ranking senior officer from one of the world's leading Pharma companies with an extensive dermatological pipe line. When I learned what his job was I listened with great enthusiasm and then I told him about the coincidence that I was following this Australian Pharma company closely and the fact that I had been thinking about his company as a potential buyer of Clinuvel. What was interesting was that he didn't know Clinuvel.

Now, are we naive when thinking about Clinuvel as a potential billion take over target as no one seems to appreciate the value of Scenesse - just look at the share price. And a senior officer from a world wide Pharma doesn't even know the name Clinuvel.

Or are we just a smal group of very pro active investors who will, some day, be rewarded for our ability to foresee the future?

Farma Zutical

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Jul 15, 2013, 5:38:19 PM7/15/13
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I forgot the main aim of my post when I was carried away with the plane story. The guy asked me about the patent rights and I said that it is my belief that Clinuvel has a strong patent position even though the patent for the composition of matter does no longer exist.
But what would, in fact, prevent a major Pharma from copying Afamelanotide and begin their own quick trials for Afamelanotide for let's say Psoreasis, Acne or any other skin condition where the anti-inflammatory effect is of the essence and not melanogenesis?

Uhohinc

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Jul 15, 2013, 6:15:15 PM7/15/13
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That's is a complex and problematic problem with no certain answer, not just for Clinuvel but all drug intellectual property.
The original peptides of which Dr Mac Hadley had over 30 separate compositional linear amino acids and the patents expired.
Cliuvel has one whereby the positioning (to my "desperate" investor understanding") is whereby an arginine amino acids placement has the optimal affect on melanocortin receptor one.

Most other abstract described Melanocyte stimulating hormone are simplified and affect all 5 melanocortin receptors.
The half-life for Clinuvels goes into minutes rather than seconds. Very important aspect.

I am expert enough in drug patent law to know that nothing is certain and its always evolving and no outcome can be certain.
The India courts just made a detrimental change to drug company's, and patients longterm by minimizing patent value.

Why would I or any investor put up money to develop a drug and then the India government let anyone make a backward engineered copy for sale for much less than even recuperating development costs. Let alone a reasonable businessmans profit even with high risk.

For Clinuvel there will be market exclusivity for differing years in different country's patent laws.

Legal maneuvering, minor drug reformulations with accompanying patents to restart the clock, and importantly methods of use and application are defining ways to protect a patent.

It's not another big Pharma that can develop it's own Scenesse like drug and orchestrate it thru the elaborations of regulators, it's some patent "troll" whom may claim Clinuvels patent infringes the troll patent.
Trolls shotgun file many patents, never intending to bring the drug to market. They stay ahead of cutting edge research waiting for a drug like Scenesse, then claim it's there's, and ask for royalty on sales or large settlement.

I know Dr Wolgen knows this, as well as Dr Agersborg was at big Pharma and industry aware.
I am confident in that Dr Wolgen used his meticulous to detail micro-managing of this threat and has taken the best and foremost pharmaceutical industry legal patent precautions and Pre-emptives.

eytan...@gmail.com

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Jul 15, 2013, 11:37:41 PM7/15/13
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Graph on this page seems to state that the patent pertaining to treatment of diseases like EPP and SU lasts until 2028, with other dates varying:

http://www.clinuvel.com/en/investors/business-development/intellectual-property

That is obviously the cash cow they have almost all their hope in. $20 million for 13 years is substantial for a company of this size.

Bottom line. The bad news is to understand the issue fully and confidently, you have to BE a patent attorney. The good news is to actually file suit (AKA "patent troll") you have to PAY FOR a patent attorney. Google "patent attorney hourly fees" and then factor in the complexity involved, technical expertise and total time required. If someone wants to patent troll, they must a) own the patent, and b) have $500,000 lying around to spend on fighting for it, with no guarantee of success.

davidl...@gmail.com

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Jul 17, 2013, 8:12:46 AM7/17/13
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I re-read some earlier post with a link to an FDA ppt on the orphan drug market protection and come to the conclusion that this is probably more important for clinuvel than all its patents together and on top of that it is the regulator that will defend clinuvel's market exclusivity, not clinuvel's paid lawyers.

Apart from that a copy of the peptide is probably not the way to take market share off clinuvel. It would be bad marketing and dangerous for any of the big pharmaceutical to venture into such thing.

First of all, only a few companies worldwide are allowed and capable to safely synthesize peptides of enough purity for human use (in EU and US) and with cGMP approved laboratories. Solvay pharmaceutical is one of them and they are not many so they won't pirate each other's market to begin with.
First semi-monopoly.

Secondly, clinuvel has likely (as stated above) tweaked the original and public formula in a specific and undisclosed way so for the moment an exact copy would be based on guessing.
Second semi monopoly.

Thirdly, the success of afamelanotide is based on the "revolutionary" beneficial way of administration via a sustained release biodegradable implant that is manufactured and developed in cooperation with Brookwood/Evonik over years of research, named Scenesse. To achieve this way of administration, safety and stability of the peptide etc is something that is more difficult than just copy the afamelanotide peptide that is published and not patented.
Third monopoly.

For the time being Scenesse is a complex technological product that can simply not be copied in a consistent way by anyone. It is a matter of time before other companies especially from China or India reach the point were they can synthesize a reverse engineered safe peptide and integrate it is a sustained release biodegradable implant that does not cause the big negative side effects of the liquid injection. Same as the mobile phones, you will have Scenesse copies Made in China at half price on the internet and they will look almost identical to the real Scenesse but they are different and less effective or even dangerous in many ways.

There are about 150 applications for orphan drugs in EU alone and last year 19 MAA with EMA. Double that for the US market and you already have 300 and 38 for orphan drugs alone. If you then look at all the other drugs including generics you quickly land at about 1000 or more drugs in development pipelines somewhere in the world. As an important person working for a pharmaceutical you are paid to manage your product pipeline and people to provide income for the next years. I would think that about 95 percent of their time goes to internal business and projects and only every now and then there is time to look at and consider external business and events. Not to say a lot of time is wasted because of hierarchy and administration etc. And then there is their specific field: they are mostly specialised and focused on 1 field only like cancer treatment or eye-treatments etc. Dermatology is mostly not high on anybodies list, let alone they ever heard about the photoprotection business (what?).

That is also why these people need external consultants to inform them about the world outside and the wonderful opportunities for synergy or take overs etc. To talk to this high exec and reveal the story on clinuvel is probably an eye opener that will make several consultants angry because they could have made good money from "selling" this intelligence. But let's not forget there is a few 1000 small and big companies developing thousands of therapies for thousands of diseases worldwide.
So for 1 busy exec to know un-marketed micro-cap clinuvel would be the lucky exception. Thanks to you he knows now and that could change everything!

Farma Zutical

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Jul 18, 2013, 11:32:27 AM7/18/13
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Bio who has JustClinuvel stated some time ago that he expects an aquisition bid between 500 and 900 million USD as far as I remember. We'll see if he is right. I doubt that many big Pharma players have Clinuvel on the radar if the guy I met doesn't know them already. Doesn't really matter, though. A take over is not attractive I think.

Uhohinc

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Apr 21, 2021, 4:36:55 PMApr 21
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https://www.fbrice.com.au/ip-news-insights/who-owns-crispr-cas9-nobel-prize-in-chemistry-stokes-patent-dispute/ It is not how good your research or patent is, it is who has the better lawyer. Even though Douda and UC Berkeley filed ahead of Broad Institute, Broad used a priority status to get ahead of UC Berkeley. 

Uhohinc

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Apr 21, 2021, 4:54:53 PMApr 21
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This above re Crspr cas technology patent dispute relative to Palatin shadowing everything Clinuvel does in press releases but poorly in execution and Luger and Bohm filing patents after being contractual to Clinuvel research vindicates the Clinuvel Dr. Wolgen meticulous information control.  I am guessing Clinuvel prevailed in the patents dispute because of the contract. Of course Luger and Bohm were used because they already were experts in melanocortin research.  I do not think Luger and Bohm ever filed a patent before the one to usurp Clinuvels.

Uhohinc

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May 9, 2021, 11:00:28 PMMay 9
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Palatin Announces U.S. Patent Term Extension for Vyleesi® (bremelanotide injection)
 

NEWS PROVIDED BY

Palatin Technologies, Inc. 

May 04, 2021, 07:30 ET

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CRANBURY, N.J., May 4, 2021 /PRNewswire/ -- Palatin Technologies, Inc. (NYSE American: PTN), a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin peptide receptor systems, today announced that the United States Patent and Trademark Office (USPTO) issued Notices of Final Determination and Requirement for Election on a patent term extension for two U.S. patents covering the Vyleesi® (bremelanotide injection) drug substance, U.S. patents 6,579,968 and 6,794,489. The term of only one patent may be extended and will have an expiration date of June 25, 2025.

Vyleesi is the only on-demand drug approved by the U.S. Food and Drug Administration for treatment of hypoactive (low) sexual desire disorder (HSDD) in women who have not gone through menopause. For more information on Vyleesi, go to www.vyleesi.com.

The patent term extension is pursuant to the Drug Price Competition and Patent Term Restoration Act of 1984, commonly called the Hatch-Waxman Amendments, which permits an extension of the term of one patent for a maximum period of five years as compensation for patent term lost during drug development and the FDA regulatory review process. An interim extension for a period of one year from the original expiration date of both patents of June 25, 2020, was granted by the USPTO in May 2020.  In the Notices of Final Determination issued by the USPTO, the maximum allowable five-year extension was granted.

Palatin has filed an Election to extend the patent term of U.S. patent 6,794,489.  This Vyleesi patent, which will now expire June 25, 2025, has claims to the bremelanotide composition of matter as well as methods for stimulating sexual response.

Additional United States patents and patent applications claim methods of treating HSDD and female sexual dysfunction with Vyleesi and have terms until November 2033.  Issued patents on methods of treatment using Vyleesi include U.S. patents 10,286,034, 9,700,592 and 9,352,013.

About Palatin

Uhohinc

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May 21, 2021, 3:25:17 AMMay 21
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Jalu06Active member
Good Morning from Germany,

some interesting insights. unfortunately this is in German.

Some IMO important information: Markus Boehm from the University of Münster was a scientific consultant for the german benefit institute and Wolgen really fronted him and the German IQWiG for choosing him 
He said that he lied in his declaration of interest conflicts and that they have legal issues since 2014.

But I don't like that Wolgen really attacked the german joint federal committee. often this leads to conflicts and in the near future, this might come back.

What are your thoughts?
At first, I was slightly amused but now I am a little bit concerned.
It seems like they were not prepared for this oral hearing. Wondering why they didn't engaged an agency for this oral hearing / process. All in all for me this representation was unprofessional 

Best regards 

Uhohinc

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May 21, 2021, 3:35:07 AMMay 21
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start of translation from just above post...........Oral hearing according to § 35 a Abs. 3 Sat 2 SGB V here: Active substance Afamelanotide (D-641) Video conference of the Joint Federal Committee in Berlin on May 10, 2021 from 14:59 to 16:14 - Stenographic Word Protocol -

 Registered participants of Clinuvel (Europe) Limited Mr. Prof. Ehlers Mr. Hay Mr. Dr. Wolgen Mrs. Dr. Quadbeck-Diel 
Registered participants of the company Mitsubishi Tanebe Pharma GmbH: Mr. Larak Mr. Dr. Brecht 
Registered participants for the city hospital Waid and Triemli, Zurich: Mrs. Dr. Memories Mrs. Dr. Barman accusations 
Registered participants for the association Forschender Dzneimittelhersteller e. V. (vfa): Mr. Dr. Rasch 3 

Beginning of the hearing: 14:59 
Mr. Prof. Hecken (Chairman): My venerable ladies and gentlemen! Welcome to the subcommittee Medicines of the Joint Federal Committee. We are in the hearing procedure, here specifically in the statement procedure Afamelanotid. This is the renewed assessment procedure after the deadline for an orphan, which is for the treatment of patients with EPP will be used. The basis for today's hearing is the dossier review of the Joint Federal Committee of 1 April 2021, to the position taken by one of the pharmaceutical entrepreneurs, that is Clinuvel Europe Limited, then as Further Dr. Jasmin Barman Aksözen from the City Hospital Waid and Triemli in Zurich, Mrs. Dr. Anna Minder, also from the City Hospital Waid and Triemli in Zurich, Mrs. Lea Kiefer and Mr. Private Lecturer Dr. Carsten Weller of the Charité, namely of the Clinic for Dermatology, Venereology and Allergology, as Mitsubishi Pharmaceutical Contractor Tanabe Pharma GmbH and the association Forschender Pharmaceutical Manufacturers.

to continue

Uhohinc

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May 21, 2021, 3:55:54 AMMay 21
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First of all, I have to establish that there is attendance, as we are also keeping verbatim transcripts of this hearing as usual. For the pharmaceutical company, on the one hand, Professor Dr. Ehlers, Mr. Hay - (Shout: He's prevented today because his wife has had a child; that's what Mr Philippe is for Wolgen there!) - It is Mr. Borgen, okay. Then we congratulate Mr. Hay, his wife and wish that the child is well and healthy and the mother is too and we say hello to Mr. Borgen. Then Dr. Wolgen to be there. (Shouting: In this case it's the same, it's Dr. Wolgen!) - I see. Mr. Wolgen is Dr. Borrow. Then we delete Mr. Borgen and greet Mr. Dr. Wolgen. Is that correct now? (Shout: That's right, Professor Hecken!) - All right, thank you. - Congratulations to Mr. Hay, to his wife and the child, however nevertheless. - Then we have Dr. Quadbeck-Diel. Then we sorted the pharmaceutical company. Then there would have to be Dr. Barman-Aksözen from the Waid and Triemli City Hospital. Miss Dr. Barman-Aksözen (City Hospital): Unfortunately, my video doesn't work yet. We are still working on it. Prof. Hecken (chairman): That doesn't matter; we can hear you well. - Then Dr. Less from Stadtspital Waid und Triemli, Mr. Larak and Dr. Brecht from Mitsubishi and Dr. Quickly from vfa is also still there. - Has anyone else dialed in who has not been called? - It can be seen not the case. Then I would first give the pharmaceutical company the opportunity to from his point of view the essential points of the dossier evaluation and of course also that of the To address the re-evaluation of submitted dossiers. Then we would go into the question-and-answer session. - Who does this for the pharmaceutical company? - Professor Ehlers, You're welcome. Prof. Ehlers (Clinuvel): First of all, thank you very much for the invitation, and the CEO from Clinuvel, Philippe Wolgen, would take over the area. Prof. Hecken (chairman): Thank you, Professor Ehlers. - Then Dr. Wolgen, you have the floor. 4th Dr. Wolgen (Clinuvel): Thank you, Professor Hecken. - For completeness: how long is the meeting today in total? Prof. Hecken (Chairman): That depends on the persuasiveness of your statements and the Number of questions to. Experience has shown that I say 45 to 60 minutes. Dr. Wolgen (Clinuvel): Okay.

Uhohinc

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May 21, 2021, 4:03:12 AMMay 21
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I'm going to keep it very short today. Prof. Hecken (chairman): You can also speak for half an hour. We have afterwards no more hearing, and the sun is shining here, it's warm outside, so, one is no longer involved used to not wanting to go out. With that in mind, do it how you'd like; no stress. Dr. Wolgen (Clinuvel): We'll make it short. - Ladies and gentlemen! Dear one Professor Hecken, Dr. Oppermann and those present! I apologize for mine bad German. Professor Dr. Ehlers informed me at short notice on Friday that I had Clinuvel must present as managing director. I didn't have time to prepare. When I found out in November 2020 that Clinuvel had to go through the same procedure as in the year In 2016, my first reaction was dismissive and I found it superfluous; because I couldn't get in put in the motive that Scenesse is once again the subject of the benefit assessment. But over the weekend I realized that this second review is actually a great opportunity; because Finance and science have two components in common: You can observe from a considerable distance, in this case five years, whether there are progressive insights, which objectively point to in-depth knowledge. The question that the G-BA should actually be asking itself is whether there would be any major changes. We'll stop for about five minutes or so Put the mirror in front of us and the G-BA, and I'll show you how we went to work here. The basic question - and keep an eye on all of these for the next ten minutes - is what has has changed significantly in the consideration of the drug for EPP since 2016? Eight essentials There were changes in the context of the benefit assessment. I call this "progressive insight" again. First: continuous PASS protocol, managed by the EMA, monitored by the BfArM in Bonn and has been checked and accredited annually since 2016. The clinical data are updated every day registered in the Central European Register. Secondly. EMA approval was granted in 2019 after re-evaluation of the data after five years without Conditions extended. Third. The continuous treatment of EPP patients in Germany at four selected trained protoporphyria centers, a total of 159 German patients per year. Fourth. Treating EPP patients in twelve European countries at the same price as has not increased since 2016. Fifth. The FDA evaluation and approval in October 2019, based on merged Study data from CUV029 and 030, with the FDA itself providing the

Uhohinc

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May 21, 2021, 4:11:29 AMMay 21
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the raw data is saved, edited and analyzed independently of Clinuvel. Sixth. The Australian Assessment and Approval 2020, with the authority itself providing the raw data edited and analyzed of three studies and came to the conclusion that there was an underestimation of the effect of the agent. 5 Seventh. Two independent international publications, led by doctors prescribing, about the real effectiveness of Scenesse in everyday life and influence on quality of life. Eighth. Annual adherence of EPP patients to the drug of 94 percent without the pharmaceutical company paying patient groups or doctors to prescribe the drug. This means that the patients and the four German doctors decide for themselves whether the drug is prescribed and not in connection with - or: without intervention - society. These are the eight essential changes that prove and quantify the additional benefit. What did Clinuvel determine and testify for decision-makers in 2016, and how did it act? Are these statements, evidence and data relative to 2021? The G-BA reviewer in the benefit assessment said in August 2016 that there are concerns and uncertainties with regard to the effectiveness. 

Our task today is to judge whether the alleged holes are now closed, where the alleged uncertainties are adequately refuted by the eight points. In other words: has the remedy proven to be effective or rather inefficient for these 159 German patients under real current, real circumstances? Before I answer this question to you and here 50 percent of those present are representatives of the statutory health insurance - what were the public claims of the GKV as a result of the benefit assessment of the agent in 2016 and in March 2017 before and during the arbitration board? First, the Clinuvel company made false claims about the drug's effectiveness. Secondly. Society had misconceptions about that Number of patients given in Germany. There would have been between 1,100 and 2,000 EPP patients which Clinuvel would treat and thus significantly undervalued the economic pressures. Third. The company had allegedly wanted to prescribe the drug off-label in order to use it To enlarge market. Fourth. The annual number of implants would not be verifiable. Fifth. The fixed price in Germany would not be the same as for the other countries, but considerably higher.

Uhohinc

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May 21, 2021, 4:17:22 AMMay 21
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But let's hold the mirror up to ourselves and analyze the five statements of the statutory health insurance that really are everything tried to fend off the drug as part of a non-quantifiable benefit assessment issued by the G-BA in 2016. First, there have been different ones over the past five years Analyzes that have proven its effectiveness. Second, patient adherence, which is unusually high in the pharmaceutical sector. Thirdly, because the price is the same in all European countries has remained unchanged for four years. It has to be said that the G-BA reviewer in The report this year conveniently mentions only four countries in which the product is sold has been. Fourth: A disease that is characterized by light intolerance is not a solar disease, but an absolute intolerance of the visible wavelengths over 400 nm. The G-BA reviewer continues to emphasize that the data would not be applicable in the German context. Fifth: The number of patients was never exceeded as determined in the arbitration award: 600 treatments in the first and 800 in the second year. Ladies and gentlemen, a bias - I don't know the German word for it - is not just the distortion and twisting of facts, anyone who has been writing professionally for 25 years knows what exactly the bias entails, that one can consciously omit facts in order to give the reader, the targeted audience, the impression that it is subtly different from reality. In this The G-BA author goes much, much further into this question. He also suggests causal Links between facts that objectively do not exist, but presumably with the intention of the reader and to influence the upcoming party GKV in order to achieve the desired goal. Today I have only time for three essential ideas of the bias and wrong ideas of the G-BA author. Page 18: Regarding the essential study, carried out in 2012, the author says today, now:

Uhohinc

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May 21, 2021, 5:41:06 AMMay 21
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 6th The patient relevance of the duration of exposure to sunlight from 10 a.m. to 6 p.m. is not immediate patient-relevant. That is blatant. If the BfArM in Bonn thinks that the FDA has helped, to develop this primary endpoint, and the author will exit into this in 2021 To determine the benefit assessment that it was not directly relevant for the EPP patients.

A second example, page 53: The author of the G-BA allows himself a new statement to the reader and To influence you, the audience. As a background: The EPP disease affects every patient a genetic mutation, regardless of whether it is from Australia, USA or Europe. While the five Studies and prescribing of the drug have appeared effective in three continents, the reviewer will now come in 2021 - in contrast to 2016 - with a completely new argument, that is not based on data or experience. He writes on page 53 - I quote: “Continue to appear The transferability of the results of Study 039 carried out in the USA to the German healthcare context is questionable, especially against the background of different weather conditions and possibly culturally influenced behavior of EPP patients. ”That is a whole new amazing argument. The three authorities, FDA, TGA and EMA and BfArM themselves actively helped design the study, and during the current real-world prescribing states, cultural and regional conditions have never emerged that affect its effectiveness. But this author cannot resist the temptation to offer the reader that it is for him It is even questionable whether the study results from 2012 are valid and transferable to Germany are.

Amusingly enough, what is being delivered here is very clear. Page 58: the author this benefit assessment is extremely selective in its reporting and knows exactly what it wants to determine from the positive FDA decision and what it leaves out for the readers. Falsified on page 58 the author is now making a statement that is not written or insinuated anywhere in an FDA document. What does the G-BA author say? He writes on page 58: “The FDA criticizes this approach also in their assessment and carries out an analysis with all randomized test persons in the case of imputation of missing values, whereby the p-value just missed the statistical significance. What wrote the FDA exactly in the original text? I quote: "The two sensitivity analyzes described above, performed by the FDA itself, yielding results that are generally similar to the applicant's analysis. ”And what context did the FDA provide that was conveniently left out of the G-BAReviewer? I quote: "We can conclude that the applicant has demonstrated that afamelanotide can increase the time in direct sunlight without pain in patients with EPP compared to placebo." There is nothing to be read of "FDA criticism" and to feel and interpret. But our G-BA reviewer cannot resist the temptation.

I now come to the facts: I admit that as a managing director I also have a bias. All that Made in Germany or made in Germany is sacred to me, and that is reflected in Clinuvels Business philosophy. But after today I'm not so sure anymore. When I did the I was able to witness the demonstration of the GKV in the preparatory phase, this weekend is for me new capital about transparency and neutrality has been added. According to the Social Security Code V. The evidence and evidence to be verifiable, objective and impartial. That applies to the G-BA and that IQWiG. The G-BA and IQWiG could have chosen from 152 centers around the world whom they would act as impartial external parties Could involve experts. Clinuvel never consciously had EPP patients treated by one university, one, namely the University of Münster; because since 2014 we have a serious one Conflict with this university that we sued. The expert, called by IQWiG / G-BA - the 7th Professor Markus Böhm - who represents the university, has a conflict of interest, what is in question 6 and 7 of the form is not filled out, and the evidence is therefore void.

Dear ladies and gentlemen! Professor Hecken! I leave you with the previous thoughts - - Today's topic and referral from the G-BA should actually have been whether the drug is under current, real, and clinical patterns are actually effective, or whether or not after five years in the commercial eviction in Germany has changed something for better or for worse, and how the pharmaceutical company behaved on the German market in relation to this promise. We took a close look at it in the mirror and our promise to the Germans Patient kept. But in return, our partner G-BA looked for irrational arguments of alleged evidence in order to continue to sow doubts. There is no evidence to dispute the extent to which the drug is effective and the evidence acquired from an expert in the field is not valid or reliable. Objectively, after 15 years of clinical treatment of EPP patients, this would not be possible more deny that the level of effectiveness is high. Only one could agree, like the EMA and BfArM confirmed that as a socially progressive society the extent of effectiveness Can only be called highly moderate after a long-term description of the remedy. We had that moment reached in December 2019. According to EMA and FDA expectation and according to the statements of 80 doctors worldwide who have researched the agent in order to publish the results has done without bias or wrong motivation proved the effectiveness as harmlessly positive; because the patients experience a dramatic new life in everyday life that they have never had before. So that's the added benefit high. But if the authors of the G-BA were correct, then one can only come to one conclusion: to accept the evidence that the Clinuvel company, all the doctors and now the FDA and TGA have misrepresented and analyzed the facts for years. Professor Hecken, I value your integrity very highly. That is my experience in the five years. We are waiting for your evaluation. - Thanks.

Uhohinc

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May 21, 2021, 5:47:40 AMMay 21
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Prof. Hecken (Chairman): Thank you very much, Dr. Wolgen, for this introduction, being it I find it very difficult to say thank you because it is very important to me regardless of my integrity is to show here that both the Subcommittee on Medicinal Products and the plenary session of the Federal Joint Committee usually make technical decisions that - that is precisely what it is became clear in connection with ten years of AMNOG - above all in the professional world distinguished by the fact that they are assigned a high degree of professionalism, objectivity and scientific evidence. Against this background, it is very difficult for me to listen when you say that, amusingly, a G-BA author or the The temptation could not be resisted to make certain selective perceptions in his dossier evaluation in order to influence the audience and then to serve the National Association of Statutory Health Insurance Funds in some way. Usually we are not.

Today's hearing is intended to answer very specific scientific questions from the point of view of the pharmaceutical entrepreneur and from the point of view of specialist medical advice and the Benches are provided. That there are contradictions in value between the regulatory authorities and the HTA authorities is nothing new either; I've been busy with that all day today. That's why it's a bit problematic for me to carry out this emotionality in this setting. We're not on a panel discussion here where they say we're going to do G-BA bashing or god knows what. 8th You said you didn't feel like discussing this. Therefore the first question: are you ready Answer questions, yes or no? If that weren't the case, then we would at this point Break it up, otherwise I would - I have no further questions after this introduction - the Open up the possibility of a question-and-answer session.

Prof. Ehlers (Clinuvel): Thank you very much, Professor Hecken, maybe I can - - Prof. Hecken (Chairman): Do we continue or is that - - Prof. Ehlers (Clinuvel): Of course we will continue. Prof. Hecken (chairman): At the technical level, then? Prof. Ehlers (Clinuvel): Yes. Prof. Hecken (chairman): Okay. - Then I will now ask the benches and the patient representatives. Any questions? - Okay, there are no questions. - I don't ask a question either. Who got in touch? - Mr. Fischer, please. Mr. Fischer: Thank you very much. - I have a question about the EPP-QoL endpoint. Can you briefly go to Carry out the validation project that you have described? You write that the instrument is partially validated, but we have no data on this. There was also something in the PASS modified version of the EPP-QoL used compared to the study. There is my question: what were the reasons for the changes? Prof. Hecken (chairman): Who would like to answer the question? - Dr. Wolgen, please. Dr. Wolgen (Clinuvel): Thank you, Mr. Fischer. - The EMA is evaluating the PASS protocol, that's one Post-Authorization Safety Study every year. In the first year we were asked to be part of the Validation to revise the quality of life study again with your employees. The lower part of the The revision has been decided to delete three questions, thus shortening them from 15 to 12. How You know, validation is a long-term process. As a sub-part of this validation, the doctors themselves decide whether to use the instrument or not. With that you have the last has used and published the instrument for five years. I think we are 80 percent in the validation process. 

Prof. Hecken (Chairman): Thank you. - Does that answer the question? Mr. Fischer: Thank you. - The preliminary validation dates you talked about the are also not yet available if I have understood correctly. Dr. Wolgen (Clinuvel): The validation data is based on four years of continuous use in the clinic, and they are saved and taken along as a sub-part of this publication. The next The second stage is that all of this data is completed in the internal validation. Prof. Hecken (chairman): Thank you. - Ms. Teupen, please, patient representatives. Ms. Teupen: We have a short question about the potential for distortion due to hyperpigmentation. Can you say something about this from your perspective? 9 Prof. Hecken (chairman): Who does it? - Mr. Wolgen again. Dr. Wolgen (Clinuvel): I think I can talk about it a lot, but I heard you have a doctor present, Dr. Weller from Berlin. It is more appropriate that the doctor himself Talking about hyperpigmentation as society. Prof. Hecken (chairman): I don't have a Dr. Weller from Berlin, who is with us today. He has commented in writing, he is not present today. We only got the two doctors out Switzerland as experts. Dr. Wolgen (Clinuvel): Okay. - Maybe it will be good if the doctors speak. Prof. Hecken (chairman): If you get in touch, you will be given the floor. So far I have no request to speak from them. Prof. Ehlers (Clinuvel): Maybe Ms. Quadbeck-Diel should comment on this. Prof. Hecken (chairman): Mrs. Quadbeck-Diel, please. Miss Dr. Quadbeck-Diel (Clinuvel): In our statement, we had shown that this risk of bias does not really exist if 81 percent of the patients saw no pigmentation, but only 19 percent. In this respect, the risk of bias cannot quite be voices. Prof. Hecken (Chairman): Ms. Teupen, does that answer your question? Ms. Teupen: Yes, thank you very much. Prof. Hecken (chairman): Thank you. - Mrs. Ludwig. Miss Dr. Ludwig: Thank you very much. - I have a question about the side effects. You have in the CUV039 study no effect estimator calculated for the adverse effects. There is the question: Wasn't that possible? Why wasn't that done? It's always a little easier for us to do to be able to assess these effects. Prof. Hecken (Chairman): Who would like to do that? Prof. Ehlers (Clinuvel): Mrs. Quadbeck-Diel. Miss Dr. Quadbeck-Diel (Clinuvel): I don't think I could answer that professionally now. Prof. Hecken (chairman): Who can answer it th

Dr. Wolgen (Clinuvel): The CUV039 study was completed in 2012, that's nine Years ago. I am happy to deal with your question. We have shown all side effects in tables, in the active area and in the placebo area. As you have seen, they are also in PASS Side effects very little, but I would be happy to send you a graph on an analysis if you want. Prof. Hecken (chairman): Thank you. - Friday deadline. - Miss Dr. Barman from the city hospital Waid, you reported. 10 Miss Dr. Barman-Aksözen (Stadtspital Waid und Triemli): Now it works with the video too. - i actually wanted to comment on the risk of bias, earlier beta-carotene, which here at EPP as a very high dose orange pigment was used as an attempt to reduce the phototoxicity prevent. That caused a visible orange discoloration in the patients, but there was various placebo-controlled studies in which no effect could be demonstrated, and The patients also agreed that it was not working. So I assume that, if an orange pigmentation does not have a placebo effect, then a dark, eumelanin pigmentation should not cause any distortion either. The patients feel this whether they get phototoxic reactions or not. Prof. Hecken (chairman): Thank you, Dr. Barman. - Ms. Ludwig, that is the question answered or is there a question? Miss Dr. Ludwig: Yes, of course it would be nice if we had the effect estimators, not just any Curves. If that works, it would be good. I have one more question for the clinicians. Prof. Hecken (chairman): Yes, please.

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Miss Dr. Ludwig: We have the end point time with direct sun exposure. Different variations of this end point were made, namely between 10 a.m. and 6 p.m. and 10 a.m. and 3 p.m. and then no to mild and moderate to severe pain. We can do the rational do not really understand these different evaluations of the actually same endpoint. Perhaps you could explain this briefly. Prof. Hecken (chairman): Thank you. - Let's start with Ms. Barman and then Ms. Less. - Miss Dr. Barman, please. Miss Dr. Barman-Aksözen (Stadtspital Waid und Triemli): I wasn't there when these endpoints were defined, but what was probably the general consideration behind it is that between At 10 a.m. and 3 p.m. the sun exposure is greatest and with it the risk of symptoms at all to develop. In other words, it is very robust during this period if there are no symptoms. However, the patients are also involved in their everyday lives. Most of the time they are at work and between 10 a.m. and 3 p.m. very few people have time to be outside. I think therefore that the longer period between 10 a.m. and 6 p.m. has left more opportunities to to experience any exposure at all, even for the patients. I think that these different times resulted from this, and one also has to regulate here; that is clear. That arises simply out of the disease.

Prof. Hecken (chairman): That seems to be logical. - Miss Dr. Minor, complementary and then maybe the company to the rationale. - Ms. Minder. Miss Dr. Minder (Stadtspital Waid und Triemli): I think the idea was to choose the time of maximum exposure to the sun, between 10 a.m. and 3 p.m. We weren't either very happy with this choice because our patients are already choosing professions that are more likely take place indoors because they have this sensitivity to light and they have also looked for hobbies, which take place inside and not outside and thus the sun exposure is naturally already reduced for the patients during this time. That is why we recently published a study where we Looking for a different endpoint that perhaps better reflects what the patients are really into 11 remember their everyday life. We called the “phototoxic burn tolerance time”, i.e. the time in which allow patients to expose to light without developing discomfort.

In this cohort, that was 10 minutes before the start of treatment, i.e. the median, and that has improved to a median of 180 minutes under treatment, which is a considerable improvement for the patients in everyday life, because they can then do things that they did not do before could: They can go shopping, queue in front of the post office, stand at the bus stop, they can Do gardening work that they couldn't do before, for example they can do one Going on a barbecue trip with friends, and that has a significant impact on the quality of life of the Patients in our study has improved significantly, from 49 percent to 80 percent with this EPP-QoL measured, which we discussed earlier. In everyday clinical practice, the effect that we have on patients is really extremely relevant see. Not only do we see an improvement in the quality of life in this light exposure time, we do also see that the pain intensity improves. Although then the patients no longer exposure, they have less severe pain. This has an enormous effect on the patients and patients, because they no longer suffer for days, but go back to their everyday life more quickly can. You feel more or less normalized. Many patients under treatment say that is life become normal, I no longer compare myself as a stranger to other people, so me I don't have to restrict myself so much because of EPP.

I think the effect with this phototoxic reaction is underestimated, which only occurs between 10 and 3 or 10 and 6 p.m. That is why we looked for this other endpoint in our recently published study. Prof. Hecken (chairman): So that I can classify it correctly: That is the end point, well Sunlight tolerance, I'll say that in the Swiss cohort of the PASS study as an additional one Endpoint was ascertained, and this is also what the publication is about. Just so we got that right on have in turn. Miss Dr. Minder (City Hospital Waid and Triemli): Exactly; this is the publication from last year. Prof. Hecken (chairman): Okay. Thank-you. - Supplements by the pharmaceutical Entrepreneur about this? - Professor Ehlers. Prof. Ehlers (Clinuvel): Not at the moment. Prof. Hecken (chairman): Okay. - Ms. Ludwig, does that answer your question or your question? Miss Dr. Ludwig: No, that answers the question. I don't know if nobody else has a question want to ask, then I just keep asking. Prof. Hecken (chairman): Yes, you do. Miss Dr. Ludwig: Okay. - We still have a question for the pharmaceutical company Use of painkillers. We do not have any precise figures on the use of pain medication per treatment arm in the study. I understand that pain medication has a limited impact on this condition, but it can do. Hence the demand as to whether it is There is data on how the use of painkillers was in both treatment arms.

Prof. Hecken (chairman): Thank you, Ms. Ludwig. - Is there any data on that? Who would? Prof. Ehlers (Clinuvel): Philippe, would you like to answer that? Dr. Wolgen (Clinuvel): Yes, gladly. - It is nearly 50 years that this disease has been somewhat in is described in the literature. From the experts it is clear that no pain relievers, no NSAIDs, not opioids, are effective in these patients, otherwise we would have the remedy for these patients not developed at all. The benefits of pain medication are zero, and patients are using it no pain relievers at all because they know there is no effectiveness at all. Prof. Hecken (chairman): Thank you. - Miss Dr. Minor complementary. Miss Dr. Minder (Stadtspital Waid und Triemli): I wanted to say that too. The patients and Patients do not respond to pain medication at all. This pain is so strong, so pronounced that they have no effect of the classic painkillers, not even with the opiates. We have in of our cohort found that almost all patients had one degree of pain on average before the start of treatment of a maximum of 10. They have all reached the maximum possible pain. The pain is then present for several days to a week and limits the patient enormously. Under Treatment does not mean that they no longer have pain, the patients also expose themselves more, however the pain intensity decreases so that on average they only reached 6 out of 10, and they were as a result, no longer so restricted in everyday life; they could go back to their work and had to Don't lock yourself in the dark at home. It also has an effect on pain intensity. Prof. Hecken (chairman): Thank you. - Ms. Ludwig, satisfied?

Miss Dr. Ludwig: Thank you very much. That were my questions. Prof. Hecken (chairman): Thank you. - Further questions? - Mister Fischer. Mr. Fischer: Thank you very much. - On the one hand I wanted to ask one more question to the company and on the other hand I would like to briefly take the opportunity to address one or two points of criticism that I have made here at the beginning was voiced. I would like to single out three points that might be a bit postponed. The Criticism that we misquoted the FDA is not entirely true. We are not concerned with the criticism on the estimator itself, but rather on the criticism of the approach that the ITT was not changed as a solving population. The FDA says it very much would have loved to see the ITT population there and not a modified ITT population as designed. We criticized that. Second: The professor Markus Böhm you quoted was included in the present benefit assessment not included at all. So, in a way, that's baseless. Last you mentioned that we used the endpoint duration of exposure to sunlight from 10 a.m. to 6 p.m. during the study have not assessed patient-relevant. That would be a tightening of the benefit assessment compared to the last time. We are actually closer to the benefit assessment from last time or from 2016 remained consistent. There we also assessed the endpoint as critical. However, we have always accepted the duration of exposure to sunlight associated with pain. That has also found its way into the final table. - So much for that part. Now, as mentioned, I would like to ask the company one more question, namely about phototoxicity and the survey in the PASS study. The number, length, and severity of phototoxic Responses should be reported by the test subjects during the past two months. At the same time, patient diaries were used to record phototoxicity. Therefore the Question: Which data are ultimately included in the evaluations and how? Can you still explain this? - Thank-you. Prof. Hecken (chairman): Thank you very much, Mr. Fischer. The question goes to the pharmaceutical company. - Thanks for the clarifications too. I would have considered this dispensable because From my point of view, the introductory lecture was not so well substantiated that one entered a professional discourse should, should or could occur. But anyway thanks for trying it right now straighten up. - Now to the question. Who does that? Prof. Ehlers (Clinuvel): Ms. Quadbeck-Diel, can you do that? Miss Dr. Quadbeck-Diel (Clinuvel): That's a lot of data, I can't give it that ad hoc now; sorry, these are multiple tables. Prof. Ehlers (Clinuvel): Philippe, do you want to comment on that? Dr. Wolgen (Clinuvel): I think it's very important for Mr. Fischer and those present, too understand that the EMA had a choice of two studies in 2014 when it approved the drug Has. This is a PAES - post authorization efficacy - or a PASS - post authorization safety protocol. We also offered phototoxicity as a long-term treatment for these patients to double check but it is not an effectiveness study. This is how it will be forwarded again. It is a safety study, and the patients themselves have to assess whether the Phototoxicity decreased, remained unchanged or increased after each implant. This is how it will be registered by doctors and patients. But I would like to emphasize again: this is a safety study and not a PAES study. Prof. Hecken (chairman): Thank you. - Mister Fischer. Mister Fischer. It has to stay that way. Prof. Hecken (Chairman): We take note. - Here you go, Ms. Quadbeck-Diel, you have the floor. Miss Dr. Quadbeck-Diel (Clinuvel): May I explain that again? - Our medicine is permitted in exceptional circumstances.

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Prof. Hecken (chairman): Indeed. Miss Dr. Quadbeck-Diel (Clinuvel): For ethical reasons it is like this: Because the disease is very rare and because there are no appropriate recognized methods, it is unlikely to be difficult to find one Prove effectiveness. For the reason that the authorities didn't impose it on us, because it just does not work. When I see all of the G-BA guidelines that you are bound by, it really is very disappointing that this cannot be appreciated or respected. Come on the hell out of it, as in normal medicine, as with other drugs, some kind of effectiveness is plucked out that is not feasible with such a drug. The patient loyalty and the Statements from patients clearly indicate how effective this medicine is, so that the is very frustrating for us. - Thank-you. 14th Prof. Hecken (Chairman): Yes, for me this is also frustrating because I actually like it It would have been assumed that we would not need to discuss the fundamentals of evidence-based medicine, which reaches its limits at certain points. We are not looking for anything “for the devil” here. I just remind you: Just if we are already coming to terms with the past, that even with the EMA mentioned several times in the CHMP, the approval process does not apply was, which actually went through so euphorically that one said, beyond any Let's look at clinical endpoints and it'll be great. I also point out that you are orphan privileged here and at least one get non-quantifiable additional benefit by law, insofar as already in a somewhat different one Situation are than others. And it is the essence of evidence-based medicine that you are under Of course, you have to try and take into account disease-specific conditions should try to map one or the other endpoint. Against this background, I am now becoming a little rude without losing my impartiality. In the end, I am already in a position to make an appropriate decision. "Hell come out ”or manipulative data presentation or the reporter here in the G-BA trying to do something for the GKV are not verbal or other criteria that we are using here. I ask you to take this into account, I ask you to go a bit further into language usage to implement. Otherwise, from my point of view, I would say we no longer need to talk to each other to chat. We are not at the regulars' table here, but we can talk about endpoints,

Against this background, I am now becoming a little rude without losing my impartiality. In the end, I am already in a position to make an appropriate decision. "Hell come out ”or manipulative data presentation or the reporter here in the G-BA trying to do something for the GKV are not verbal or other criteria that we are using here. I ask you to take this into account, I ask you to go a bit further into language usage to implement. Otherwise, from my point of view, I would say we no longer need to talk to each other to chat. We're not at the regulars' table here, we can talk about endpoints, we can talk about CHMP, we can talk about EMA, we can talk about BfArM, but then please be specific. - Now Dr. Less. Miss Dr. Minder (Stadtspital Waid und Triemli): Thank you very much. - Because of the benefit assessment, I wanted to point out that there is a point besides the light exposure time that we have in our data could objectify, and the reduced pain as well as the improved quality of life. The we have objectified everything in the study that we published last year that we in our Patients also have a very high level of therapy adherence. We examined that, it was over 95 percent. This fits in with the adherence to therapy in other studies that were carried out on EPP with afamelanotide. That seems to be a continuous good therapy adherence - - So the patient adherence to therapy is excellent. If you compare that with adherence to therapy for other chronic diseases - I went into the literature there - then it is around 45 there up to 75 percent. That is a lot deeper.

This suggests that the patients themselves consider this treatment to be very effective. Which patient takes a pain reliever several times if it is of no use? Or he tries once, maybe twice, but then he stops. The therapy adherence is on the one hand from Effect that the patient himself notices influenced, but also by the side effects that a patient experiences developed. If he has severe side effects, he stops doing them too. The high therapy adherence in I was very impressed by these data, which we examined, especially when one Bear in mind that patients often have to bear a considerable burden for treatment. This is not a tablet that you swallow, but that is an implant under the skin that is a little is painful. It's not bad, but it's not comfortable. They have long journeys, they Sometimes they have a day off that they have to give up because they cannot go to work. you have the financial burden of the journey.

In this context I would like to mention that I have had patients who came to Switzerland from the USA every two months for the implant, who made the journey, the time difference, because they considered it so effective. I think that is not a direct measure of effectiveness, but a very good indirect measure. I would like to ask that this be taken into account in the benefit assessment, because it seems to me to be extremely important in relation to the data that we publish on light exposure. A second point, if I may go on, would be that there are also patients who are sensitive to artificial light or have complaints in winter. That was back in 2006 published. In the UK, 43 percent of EPP patients experienced winter symptoms had. In my experience in my everyday clinical practice, this percentage should be even higher. This is probably due to the use of modern light sources. The LED lamps and the halogen lamps, which are increasingly used, have particularly harmful light sources for EPP, and this is increasingly restricting patients, also in the workplace. I know of one Patient who worked in a hospital. There you changed light sources, and suddenly you could she stopped working there because she was not continuously treated with afamelanotide.

We have also seen that our patients improve their quality of life with every implant that we have apply, even if we give more than four implants per year, i.e. also with the fifth and the sixth still. We have not yet been able to publish this data. We hope that we we will soon be able to do that, but we have observed it. If we can treat the patients more, that means that we can make the winter break shorter. That is, the complaints decrease in winter, but the second effect is that the discomfort decreases in spring, because the first implant in the year usually does not develop its protective effect immediately, but only with it the second and third implants achieve full protection. It's similar to when we Going out into the light and in the sun in a healthy state. When we tan, we don't have it first Day when we lay in the sun, a brown skin, but that takes a while. Something like that it with afamelanotide. The maximum protective effect is only after the second or third implant in the Year achieved.

If we can do the treatment consistently, then it is so that one no longer has to start from scratch. This means that the particularly aggressive light in spring is weakened, and the EPP patients have fewer symptoms in spring. The light is particularly aggressive because of it has a bluish component and is therefore harmful to EPP patients. Especially for the patient it is like this: We are happy when spring comes and there is sun and light outside, and we go out. It is exactly the same with EPP: Then they have to isolate themselves, and that is also extreme psychologically difficult for the patient. - These two points are very important to me, so that I can say them could. I thank you for giving me the time. Prof. Hecken (chairman): Thank you, Dr. Less. - Miss Dr. Barman. Miss Dr. Barman-Aksözen (Waid and Triemli City Hospital): Thank you very much. - I still wanted to go to the PASS make an addition. Of course, it's not a randomized controlled trial with a control group. There were also slight deviations in the protocol, and from our point of view it is not optimal, like that Effect is measured. But there are definitely things that are measured in the PASS that make the Show effectiveness. As Ms. Minder has just said, adherence to therapy is recorded, officially as an endpoint to show effectiveness because EPP doesn't have good endpoints. It is very complex to measure light exposure in everyday life. There is no standardization, there is weather 16 conditions that change. Tuesday

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e Patients have adapted differently in their lives and have jobs that mostly take place indoors. So it's very difficult. There are also no interpretation aids in the sense of: what is normal light exposure or a target value? That has not been measured or standardized. Therefore, I believe that what is measured with the PASS is still a good indication that that there is effectiveness. For example, it is recorded how much the patient is outdoors hold up. I was there when evaluating the PASS data in the Netherlands and was attended to by doctors drawn in there. There it was six hours more per week than pre-treatment. So I think that we have a kind of best evidence among the given, really very restrictive ones Circumstances that cannot be changed either. I also think that therapy regret is a patient-relevant endpoint in the case of EPP, because patients can feel for themselves whether a drug is working or not, within minutes; well, otherwise you just get burned. After all other therapies that have been tried before, no patient asks anymore. There is no one to practice any other approach or afterwards would ask because it just has no effectiveness. Therefore the PASS is not optimal, but I believe that there are things there that could easily be used. Prof. Hecken (chairman): Thank you, Dr. Barman. - Now I still have Mr Dürr as a topic-related patient representative. - Mr Dürr, you have the floor.

Mr. Dürr: I am a patient and therefore a user of afamelanotide. I am now 51 years old. I had to hide in the dark for so many years because I just couldn't get into the light. We have to be clear: it's about the light, not the warmth. That means, even at minus 10 degrees, when the sun shines it hurts me. It just hurts my skin, it makes me terrible Pain. If you overdo it, you lie in the dark for two or three days, you cool off the hands, the face, you don't know how to suppress the pain in any way. It's been a completely different life since I've been treated with afamelanotide. Otherwise you can do that not introduce. You can do things that you could never have done in the light. I can with mine Family go shopping, I can do anything a normal person does. I can mine Coming to work, I can do my work, even though I have a job as a teenager chose inside. It would be unthinkable to do a job that you can somehow use sunlight should have done. So, as I said, it's a completely different life for me. I do not want it miss more. I live near Stuttgart, I always go to Zurich to see Ms. Anna Minder. These are for I really do quite a long trip, especially now, for example, in the time of the corona pandemic. Traveling to Switzerland is not that great now, nor is it that easy. It costs too. As I said, you have to get up pretty early. If you want to keep the appointment at 10 a.m. in Zurich, you leave at 5 a.m. It's a 500km round trip. I have to still make additional payments of 80 francs per implant. I have to take a vacation for this. Do that I like everything very much, I don't care about anything, the main thing is that I get the medication and can my life Go on living as in the last four or five years. I am now in my fifth year of treatment. Like me enjoy this life meanwhile! As I said, I am only a layman, I can only describe it to you in an amateur manner. With all the medical things, I can't follow some things, but off

In my opinion, the patient's perspective, it has become a wonderful life. - So much for a little statement from me. Thank you for the time. Prof. Hecken (chairman): Thank you for this statement, Mr. Dürr. I allowed that because it was very impressive and because I didn't want to underline the pharmaceutical company's opening statement about the blatant injustices. I wanted to point out patient advocates usually have to ask questions, but it was impressive nonetheless, and we log what you have shown. - Now Ms. Hauke, then Dr. Rose and then I would also want to slowly bring this hearing to a final endpoint. - Frau Hauke, please. Ms. Hauke: I am a patient representative in the self-help EPP. I thank the two clinicians because they conveyed very well what the treatment is about. From my experience in the many years and mother of a daughter with EPP: You have to understand: people with this disease have that from birth. They learn very early what they cannot do. They are maximally adapted and conditioned. Patients who come into treatment first have to learn about these new ones Freedoms to deal with. What is a big problem - that's what Ms. Minder and Ms. Barman said - when the patients are treated with four implants, i.e. eight months, with it on In the beginning it takes a little time before the drug works, they completely fall into their fears in winter back and need a while with the new implant next year to get back to - - I think that is also noticeable in the questionnaires. - Yeah, that's actually what I do wanted to say. A year-round treatment like the FDA and how it is possible in Australia would give many of our patients a better quality of life. - Thank you.

Prof. Hecken (chairman): Thank you, although we are in the relevant licensing context act. That now has less to do with the G-BA's benefit assessment, but we're also taking that note that we will also take this on record because we will of course - and I will say that now without any cynicism - see the very considerable suffering and suffering of the patients. That is why I am now also giving Dr. Rose still has the word, regardless of whether or not he asks a question or makes a case report. But I also ask - I will also be doing this in this session - the patient representatives, in future the to instruct topic-related patient representatives in the course of the training courses to the effect that primarily not the formulation of wishes and expectations or the submission of case reports or other things are in the foreground of such a hearing, but rather asking questions. But that is a job that the Patient Representation Unit has to take on. But as I said, I am now allowing this in order not to stall the discussion. - Dr. Rose please. (short-term clarification of technical difficulties) Dr. Rose: Is it working now? Prof. Hecken (chairman): Yes! Yes! Who is Kurt? I am a little surprised now because woman Dr. Barman here [editor. Note: in the chat of the video conference program] writes to a Kurt. I see, Kurt is Dr. Rose. This is then the topic-related patient representative. Yes, okay. Thanks. So, We note in the minutes that Kurt, who was addressed in this way by Ms. Barman, is the topic-related patient representative Dr. Kurt Rose is. - You're welcome.

Dr. Rose: I am also a patient with EPP. I can only join the two previous speakers as patient representatives, and I do not want to repeat that either. For me, taking is with one 18th really tremendous quality of life improvements. I also had the problem with the four Implants, which has already been hinted at here, and would like to derive a question from this, how do you get it I would like to know: Is there any indication of the number of implants in the Year? And a second question that arises for me: Does it also apply to the new approvals again comments on the age information? Because this conversation was or there were clues about 70 and the like, ... (acoustically incomprehensible) taken? Prof. Hecken (chairman): Thank you, Mr. Rose. - Who are you directing this question to? Dr. Rose: This is my first time here. It is not yet clear to me who will answer that can. But these are the questions for me as a patient. Prof. Hecken (chairman): Yes, well, we are asking questions to the pharmaceutical company and the clinical experts. So I ask the pharmaceutical company if you can understood the question. I know the conversations that may be with regulators in Europe conversations about admission frequency etc. pp. not. That also has for the benefit assessment no effect, but we still like to discuss this question: Can you answer this question? Perhaps the clinical experts whose patient you seem to be obviously able to do this Answer question? That is why I had just recorded that Kurt was the patient representative, Dr. Rose is, apparently, well known to those who appear here as clinical experts is. We just heard from a patient representative that he was talking to a clinical expert here in Treatment is. So who can give me an answer from the company or the clinical experts? The G-BA does not answer any questions; because we don't know the facts. Against this background it is slowly becoming idle. But here you go, Professor Ehlers. Prof. Ehlers (Clinuvel): Thank you for your calm tour. - I think if Dr. Wolgen say something about it.

Dr. Wolgen (Clinuvel): Of course. - At the beginning, in 2014, when we discussed the admission requirements with the EMA, - I am now speaking to Dr. Rose in lay terms, in lay words - came out, that is, a label that doctors appropriate a maximum of four implants per year can prescribe, but with a maximum of six. But that depends on the decision between doctor and patient. So, the maximum limit is six, but the most common is four. I can Tell you our position as a pharmaceutical company, with all countries, with all authorities in the Countries where you have to negotiate how a product comes onto the market and so in Germany too, a maximum number per treatment per year was determined in 2017. To stay within this treatment maximum, most clinicians have said we will only get four implants a year deliver, although doctors are qualified to prescribe a maximum of six per patient. But we wanted them Threshold not to cross the border in Germany. So that's limited. Regarding your question of how it will look in the future: We are currently talking to the EMA about the patient like in America and Australia to be able to give the therapy all year round. But that will also be of depend on the discussions with the G-BA and the GKV. Prof. Hecken (chairman): Thank you. - Are there any other questions? Miss Dr. Minder (Stadtspital Waid und Triemli): I would like to say for the record: Dr. rose is not being treated by me. 19th Prof. Hecken (chairman): Okay. - Then we'll take that on record. Then you know him just.

Miss Dr. Minder (Stadtspital Waid und Triemli): No, I don't know him either. Prof. Ehlers (Clinuvel): I had reported in the chat, if we get to the end Prof. Hecken (chairman): No, I just wanted to - - Oh, you don't know each other, but Are you still writing to Kurt? Miss Dr. Minder (Stadtspital Waid und Triemli): No, that was Ms. Barman. Prof. Hecken (chairman): Yes, yes, good. OK. Miss Dr. Barman-Aksözen (Stadtspital Waid und Triemli): I am a scientist and have given lectures in the German self-help EPP and was a member, so we know each other. This is a very ... (acoustically incomprehensible) Prof. Hecken (chairman): It doesn't matter. - I just took note of it, but we've cleared it up now. - Professor Dr. Dr. Ehlers, you reported. Prof. Ehlers (Clinuvel): Thank you very much. - I just wanted to thank you, despite this special introduction by the company. The main points that we wanted to make are in the written statement from the pharmaceutical company, and ask for your understanding. Prof. Hecken (chairman): Thank you. - You don't need to ask for understanding, sir Ehlers, you know that we handle every situation appropriately and, as I said, we do not allow ourselves to be influenced in our impartial and evidence-based decision-making. With this in mind, there is nothing to worry about. I thank myself. I take that as a final word, Mr. Ehlers, or should another closing word be added? - That's not the case. Thank you for this hearing, thank you for the comments that have been made and finish this hearing. - We continue the meeting of the Medicines Subcommittee with one Hopefully the hearing will proceed in a more conventional manner tomorrow morning, as stated in the agenda. The session is over for today. I wish everyone involved a nice rest of the day. thanks beautiful. The hearing ends at 4:14 p.m.

Uhohinc

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May 21, 2021, 12:48:09 PMMay 21
to Clinuvel Afamelanotide SCENESSE senescence CUV ASX.CUV CLVLY ur9
My opinion, Dr. Wolgen made his point with the 8 points that since 2016 (and all independent and not influenced or nuanced or interfered with by Clinuvel) that add tremendously to Afamelanotide positives with EPP.
 My opinion Dr. Wolgen made his point of the not relevance, and the use of not factual, and the incompetence of the argue and the unreasonable by the 2016 claims made to stop Afamelanotide in Germany, and added on the now recent claims that German EPP patients perhaps have no relateable for geographic and social behavior reasons that he does not deliniate or even attempt to define.
What may be the cultural differences, is I see a couple comments from the German contributors on sharetease overtly implying that Dr. Wolgen crossed a politeness line. I think the circumstance, from my American social interactive conflict and resolution behavior we all experience in everyday life was called for. In my opinion, the German  that was countering and argue against Afamelanotide for EPP in 2016 and now in the constant reevaluating and reapproval that is constantly going on for Afamelanotide had already crossed the line of politeness and tact and personalizing with strong inference of the integrity, and truthfulness of Clinuvel in 2016 and bringing up more salacious heresay, and innuendoes against Clinuvel.

I can see the do not bite the hand that feeds you trope, and it does make sense, but being nice did not and was not going to get Dr. Wolgens point accross. I think the time for nicety was over and it was probably the least best response of not any good response at all.   I think Dr. Wolgen adeptly and professionally did to the German what the German was doing to Clinuvel and Afamelanotide for German EPP patients. But Dr. Wolgen factually and with rational and of course with first hand experience and knowledge with living this Afamelanotide for ePP was able to make the German report writer look to have an incompetent understanding of the EPP and the patient on Afamelanotide and all the studies and data.

His argue was a reach, as pointed out by what the Germans and others on sharetease had a mental takeaway in that how silly to say the German sun and German EPP is not relateable to the studies CUV in not having German patients in Germany.

I do not think Clinuvel really had a good choice here in that the bureacracies get to "approve" Afamelanotide over and over with the same story that has been done but keeps coming back, Dr. Wolgen did fight back as well as could be under the circumstances, and Clinuvel fought back in 2016 and prevailed. Which I think Dr. Wolgen made an excellent presentation, in that nothing has changed for the negative since the German approval in 2016 except for the better in independent and additional positive for approval and continued use of Afamelanotide  to the 2016 evaluation.......his 8 points.

While the present German evaluator was trying to use the same old tired points and argue what has been done over and over with Afamelanotide starting with EMA, the British, the FDA ..............

Uhohinc

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May 21, 2021, 2:29:56 PMMay 21
to Clinuvel Afamelanotide SCENESSE senescence CUV ASX.CUV CLVLY ur9
From Mitsubishi Tanabe viewpoint, I can not blame them for listening in. MT is using the same Quality of Life assesment, and personal diary between sunlight hour that Clinuvel used, created by Dr. Minder.
Every argument the regulators have brought up against Clinuvel.....should......be the same arguments MT will face. The price/cost of the drug, the number of patients, the integrity of the data indicative of a benefit to an EPP patient, and so few patients. My guess is MT will "find a way" to make sure those patient diaries are stellar results in the MT EPP trial phase III.

But as in chess as in real life, I have thought the game exemplifies how important it is to think the farther and the most moves ahead as the opponent. This has to be discouraging for MT, as there are not many commercial EPP patients and no government wants to pay for it even if MT gets approval. And as always, in the back of conscious minds is the use of msh for a not medical tan. Which a pill is soooooooo much more prone to abuse of prognosis by the internet public. And already has been.  But we all have turned up a road and then realized it is a dead end or a cul de sac, the difference is MT gets to read the signs already knowing an mcr1 agonist is a commercial dead end already occupied by Clinuvel. With what was known and to traverse the best road for Clinuvel was Epp way back before so many options with mcr1 et al, but it makes no sense financially for MT to go this route today with so many theraputic options for melanocortins........One big question, that I think I know the answer, is can MT go after melanocortins with any type or changes of it's drug other than mcr1............................................................

 An mcr1 for a photodermatological theraputic tan is not just a potential MT pill with systemic to all the body, as opposed to a Clinuvel in therapy for any photoderma disorder with a systemic mcr1 implant.................I would give more weight to the oral pill for ease of manipulation of the dose and withdrawl immediate compared to a Clinuvel surgical procedure of implant taking all day, but I think for photoderma a transdermal carries all the weight of evidence of commercial and regulatory favorability.

Dermislogon or Mt-7117 must be coated with something to survive the stomach acids and enzymes and then make it to the small intestine intact for absorption thru the mucosa of the intestinal and then past the endothelial cells with other digested and then survive the immune cells awaiting on the other side of capillaries for circulation and then the liver ...........................but can it be made into a transdermal with the latest breakthroughs........?............my guess is no. That is why I think MT is going after sclerotic disorders.
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