Opportunity for Feedback on Development and Dissemination of Educational Materials on Rare Disease Drug Development
CDER Opportunity for Feedback on Development and Dissemination of Educational Materials on Rare Disease Drug Development OPEN
2023-03-20 2023-03-20 2022-12-28 2023-03-16 2023-03-20 2023-03-20 2023-03-20 2023-03-20 2023-03-08 2023-01-23
FDA-2022-N-3226-0014 FDA-2022-N-3226-0016 FDA-2022-N-3226-0002 FDA-2022-N-3226-0010 FDA-2022-N-3226-0015 FDA-2022-N-3226-0023 FDA-2022-N-3226-0022 FDA-2022-N-3226-0021 FDA-2022-N-3226-0008 FDA-2022-N-3226-0004
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https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0014 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0016 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0002 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0010 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0015 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0023 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0022 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0021 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0008 https://api.regulations.gov/v4/comments/FDA-2022-N-3226-0004
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Comment from Praxis Precision Medicines Comment from Chiesi Global Rare Diseases I am a parent of a child who died of a rare and fatal neurodegenerative disease. I am also a registered pediatric nurse. My comments were published as a letter to the editor of Update Magazine and are shared with permission from the Food and Drug Law Institute. After reading the article, Senate Bill and FTC 6(b) Study Turn the Heat on Pharmacy Benefit Managers Amid Drug Pricing Concerns, by Tiffany Jang  David Shotlander, I thought about what I recently learned about the drug Zolgensma, approved by FDA in May 2019 as a gene therapy to treat Spinal Muscular Atrophy (SMA) in children less than two years old. The gene therapy is a one-time intravenous infusion treatment that may eventually become the standard treatment for SMA.[1] In 2019, it was the most expensive drug the world had ever seen at $2.125 million.[2]I recently attended a Newborn Screening Bootcamp hosted by the EveryLife Foundation for Rare Diseases. At the conference, we were told by a genetic counselor that there are 428 fundraisers on one online fundraising platform, created by families that are raising funds for their children with SMA, and that many of these families are seeking donations for the gene therapy, Zolgensma, and associated medical costs with SMA.Access to a rare disease gene therapy is not a question of availability, but of cost. Drug companies set their own prices when selling the products they have created. Without any competition for a gene therapy like Zolgensma, these companies can set whatever price they want.[3] The price tag of $2.125 million makes the drug unobtainable for most families. Additionally, insurance companies can make it difficult for families to access these expensive treatments. Prior authorization (PA) is a common health insurance practice to ensure that the treatment is medically necessary, and it continues to frustrate patients.[4]Zynteglo ($2.8 million) and Skysona ($3 million) are gene therapies approved by FDA in 2022. Along with Zolgensma, they are the three most expensive drugs the world has ever seen.[5] There are hundreds of gene therapies currently being developed and in clinical trials.[6] When any of these therapies are FDA-approved, families will not be able to afford the multimillion-dollar price tags. Will there be thousands of families creating online fundraisers for these gene therapy medicines?To avoid this possibility, we need new reimbursement models that can ensure appropriate patient access to much-needed treatments. One approach suggested by Senator Cassidy from Louisiana is for Medicaid, or some other government program, to pay for gene therapies, so commercial payers would not have to cover them. Instead, it would be fully funded by public funds. Society, as a whole, pays for these therapies as opposed to the insurance pool to which the patient belongs at the time the therapy is given.[7]Gene therapies are potentially curative for many terrible rare diseases. Rare disease patients need a way to pay for these medicines.[1] Carmen Fookes, Why is Zolgensma so Expensive? Sept. 5, 2022, https://www.drugs.com/medical-answers/zolgensma-expensive-3552644/ (accessed Nov. 16, 2022).[2] Christopher Rowland, The FDA Approves a Gene Therapy that is the Most Expensive Drug in the World. The Washington Post, May 24, 2019,https://www.washingtonpost.com/business/economy/the-fda-approves-a-gene-therapy-that-is-the-most-expensive-drug-in-the-world/2019/05/24/57c66500-7e4a-11e9-8ede-f4abf521ef17_story.html.[3] Julia Hawley, How Pharmaceutical Companies Prices Their Drugs, Sept. 30, 2022, https://www.investopedia.com/articles/investing/020316/how-pharmaceutical-companies-price-their-drugs.asp, (accessed Nov. 16, 2022).[4] Allison Inserro, How Prior Authorization Can Impact Patients with Rare Disease. Feb. 28, 2022, The American Journal of Managed Care, Feb. 28, 2022,https://www.ajmc.com/view/how-prior-authorization-can-impact-patients-with-rare-disease.[5] Leigh Ann Anderson, 10 Most Expensive Drugs in the US. Oct. 17, 2022, https://www.drugs.com/slideshow/top-10-most-expensive-drugs-1274 (accessed Nov. 17, 2022).[6] Press Release, FDA Continues Strong Support of Innovation in Development of Gene Therapy Products. U.S. Food and Drug Administration, Jan. 28, 2020, https://www.fda.gov/news-events/press-announcements/fda-continues-strong-support-innovation-development-gene-therapy-products.[7] Bill Cassidy, How Will We Pay for the Coming Generation of Potentially Curative Gene Therapies? June 12, 2019, https://www.statnews.com/2019/06/12/paying-for-coming-generation-gene-therapies/ (accessed Nov. 17, 2022). Comments from the Rare Disease Company Coalition Comment from GenSight Biologics See comment letter from BioMarin Pharmaceutical Inc. Comment from Aeglea BioTherapeutics Inc. Ultragenyx Pharmaceutical would like to thank the agency for the opportunity to provide comments. Comments from Stealth BioTherapeutics Regulatory considerations for rare disease drug developmentWith increasing use of next generation sequencing, new very rare monogenetic diseases are more and more diagnosed, ending an often long diagnostic odyssey. Some pathogenic variants affect only one or a very small number of individuals (N1+). In these circumstances, standard clinical development, including randomized controlled studies for dose finding, safety and efficacy are not feasible. Further, many of these extremely rare diseases have a severely debilitating and life shortening course. Some of these diseases could be beneficially impacted with individualized precision drugs, such as antisense oligonucleotides (ASOs) and other emerging therapeutic modalities. However, costs and timelines for a standard preclinical development and CMC package are prohibitive when developing therapeutics for one or only a handful of individuals. This situation represents an ethical dilemma and a grave healthy inequity, leaving devasted families scrambling to find a therapy or fund a therapeutics development for their (dying) child.While the agency has issued draft guidances for sponsor-investigators examining individualized ASO drug products for severely debilitating or life-threatening diseases, uncertainty remains if the agency would consider the same guidance for a commercial sponsor, and if the guidance was applicable for an ASO that could treat a few patients (i.e. more than two patients, but too few to permit conduct of a meaningful controlled clinical trial). Further, to the best of our knowledge, there is no guidance for a commercial sponsor seeking approval for an ASO that is being investigated in a single or very few individuals with no or very limited existing longitudinal disease data to use as non-treatment controls. EveryONE Medicines, a private biotechnology company committed to develop individualized precision therapeutics, including ASOs, for N of 1 or a few (N1+) pediatric patients with a severely debilitating and life-shortening monogenetic CNS disorder, would appreciate feedback from the agency on the following regulatory considerations:1) Are the draft guidances for sponsor-investigators also applicable to commercial sponsors, given that the medical urgency for individualized ASOs for a single or very small number of patients is the same?  2) Are the draft guidances also applicable to examining an investigational ASO in situations with more than two patients, but too few to permit conduct of a meaningful controlled clinical?3) Opportunities to demonstrate a favorable risk/benefit in such very rare cases with the goal to get approval for an individualized precision therapeutic.Thank you.The team at EveryONE Medicines