Notes - FDA Meeting - EPP
Meeting hours 10 AM - 4 PM
Location: FDA, Silver Spring
Town Hall style. The biggest turnout in FDA history for this kind of meeting.
5 people with EPP will comment on their daily life with EPP.
KENDALL MARCUS, Director, FDA
Dr. Kendall Marcus began by saying that they would not be discussing any
particular drugs or regulatory paths for any drug related to EPP.
It’s all about risk benefit. We are here to hear the voice of the patients.
HENRY LIM, MD
Epidemiology and natural history of EPP.
Prevalence: Europe generally 1:100.000 / Japan 4:100.000
U.K.: 389 subjects identified
Median age: 34
Mean age of diagnosis: 12 yrs
Sunscreen does not protect well because EPP is triggered by visible light
JOYCE TENG, MD, Stanford
(She is the one using Cimetidine for EPP)
Treatment approaches for EPP
Talking about Beta-carotene. Doesn’t work, she says.
She encourages physical protection. Clothing, tintet windows etc.
SCENESSE
Scenesse: Very exciting peptide.
Binds to MC1R-MC5R (!)
Phase 3 trials underway ?!? No EPP trial is ongoing. What is she talking about ?
She refers to NEJM report.
Results: Pain free time improves with treatment.
Limitations: Invasive
Does not provide visceral organ protection
Lack of safety in children
Long term implications. What will increased time in the sun do ?
Does not protect the liver.
CIMETIDINE (OTC) for children:
Case study of 3 pediatric patients.
Cimetidine 30-40 mg/kg po divided BID.
Results: Rapid improvement in pain and photosensitivity <4 weeks.
No adverse effects.
Quite amazing, she says. Liver functions normalized very quickly.
Positive global feedback from patients.
Non invasive.
PATIENT AND CAREGIVER INPUT
Symptoms and treatments
5 EPP patients describe their pain. It’s excruciating, as we all know.
The first patient (adult woman) participated in the US Scenesse trial. It was absolutely life changing. She could now for the first time stay outside and do normal stuff with her family and friends. Even being out 30-60 minutes was life changing. It is very hard to spend 6 months living normally and then go back to the dark.
Second patient, 11. yrs old. Can only tolerate 10 minutes of direct light before a reaction.
Reactions last up to 5 days. Very painfull. Can’t do anything outside. Her twin sister gets to play outside. (My comment: This is heartbreaking to listen to). She wants a treatment that will allow her to stay outside all day. Cimetidine DOES NOT HELP this little girls, she said (!)
Third patient. Adult man. Describes the pain. It doesn’t go away ! Every day he fells incomplete because he can’t pursue his dreams. It’s like putting your hands in boiling water. He gets overheated in the summer because of the clothing. In the winter it’s easier. He joined the Phase 2 Scenesse trial. The treatment helps. It was very hard to push himself into the sun, so he tried a little bit at the time. The recovery was amazing. He asks the FDA for help. Emotional pain is worse than the physical pain.
Fourth patient. Female teenager. She is crying while talking. The curtains in her house are always drawn. The only thing she can do is cover up. There is no medicine in the US that helps. She is very emotional. (My comment: Come on FDA - help these people). She is only 16 and she knows that Scenesse is for adults. But she is so excited that when she turns 18, perhaps she can have it. She wants to go to the pool in the day light. This girls was very emotional
Fifth patient. Adult female. She had a 5th grade teacher who didn’t believe her. Caused her trauma as a child. She is in a reaction from traveling to the meeting. Even the computer screen gives her a reaction. But it is worth it. Even when covering up she gets a reaction. Imagine telling your kids to not touch you, because it’s too painfull. When she has a reaction she wants to rip her skin off. Her kids don’t have EPP so they can be outside. She misses out of all their events. She is also very emotional. She can’t do anything with her family. It affects her friendships. She can’t attend work events. She is a trauma therapist but because of her EPP she can’t put her skills to work.
LARGE GROUP DISCUSSION
EPP patients describe their pain. There aren’t words, one says. An other says that it’s like cutting yourself and burning at the same time. A parent says that the pain her child suffers is so severe that the child has walked around with a broken leg without even knowing it because the EPP pain overshadowed it.
AFTER LUNCH:
The moderator asks how many are traveling to Europe. There is a show of hands. Not visible though. They ask what patients do to treat the condition. 0 % say Cimetidine / Tagament. 92 % say Protective clothing or masks / lifestyle changes.
A gentleman says that he tried Cimetidine and that it did nothing. A woman says that her daughter took it for a year and that it did nothing at all. 3 people in all say that Cimetidine was not meaningful. (Why did they have Dr. Teng up there for 20 minutes talking about Cimetidine for so long time when it’s not meaningful ???)
A gentleman was in two trials. Second time around he got Scenesse. It helped him so much that he could skip the mask and didn’t have any reaction. Very thankful for that. A woman with two adult kids with EPP thanks the FDA for listening. She wants the FDA to understand that they are talking about pain management - that is what people is asking for.
A gentleman says that he tried beta carotene and it did nothing. He got Scenesse and didn’t have one single reaction. He even got a sun burn and loved it. The following summer was horrible because he was no longer on Scensse and returned to be able to do nothing.
Another gentleman was in the trials and is now traveling to Europe. It is beyond his wildest dreams what Scenesse is doing for him. It has taken him 1,5 yrs to understand what he is able to do now. He is amazed how much time he can now spend outside. This is what he is looking for in a treatment. It has surpassed his wildest expectations.
JT’ mother: JT has been fortunate - has done 5 trips to Switzerland. Her prayer is that everyone with EPP will have access to Scenesse. It is life changing.
They now talk about how to re-learn a behaviour.
A woman talks about Scenesse. She has been to the beach for the first time because of Scenesse.
OVERVIEW OF FDA REGULATORY PROCESS
This I didn’t listen to. Had to take a call.
CHALLENGES IN CLINICAL TRIALS DESIGN FOR EPP
Dr. Elizabeth Minder
We have cared for more than 100 patients, she says.
Talking about all the challenges.
Pigmentation may produce a bias in a trail.
Afamelanotide is described as life changing. A compelling evidence of
efficacy.
Elizabeth Minder: We have more than 500 patients in Switzerland (?)
PANEL DISCUSSION
Talking about the willingness to participate in future clinical trials.
Why do they talk about future trials ? Are they planning more phase 3s or
perhaps a phase 4 ?
Now Kendall (I think) says that it’s about building on the results they have. Like in the treatment of HIV back in the day. Also for pediatric patients. What can be made available to them ?
Safe and effective dose ? That is the purpose of the discussion, she says. She has heard from many today that they want for the children to benefit. That will be a challenge finding a treatment. (It sounds as if my worries about why they are talking about new trials are not warranted. This is for the children and possible future trials.)
DR. Desnik says that the most important in a trial design is to understand the natural history of EPP. When you’re burned for the first time you will have a inherent fear of the sun and will try to stay out.
Dr. Minder: We have a decade of experience in measuring efficacy in EPP.
Dr. Teng: We need to hear what the patients want and that is to spend more time in the sun.
Patient reported outcome.
There have been many trials. And people believe it works. That’s the best criterion I can think of, says one of the experts. Strong support for Scenesse.
Dr. Marcus: We hear you. But we need to be able to put it on paper. So far we have only been able to measure small levels of benefits. We have to measure it all to demonstrate efficacy. She is also referring to all the letters she has received from the APF.
Dr. Minder: We have to do as we did in the phase 3 trial. You cannot use average on day. But if you use integral you get a more adequate view on efficacy. There is a strong increase in sun exposure time. We will not find anything better.
Dr. Marcus: I don’t want to stop with one solution. Someone in the audience shouts someting.
It sounds as if it’s about Scenesse. Dr. Marcus: This is not a statement about a drug. There has to be a certain amount of… Believe me… I understand the frustration. We’re really trying to focus on… as I said… pediatric clinical trials might be a trial where you have 5-10 patients….
This is not commentary on anything that has already transpired. It would be great if we could all work on a path forward.
Dr. Lim: I’d also like to se more robust endpoints. But nobody wants to get burned. They have a fear. How do we do it better ?
I missed everything from here till the end. Please fill in.
