RARE Daily

October 28, 2020

Rare Daily Staff

The U.S. Food and Drug Administration granted Rare Pediatric Disease and Orphan Drug designations to Passage Bio’s gene therapy for Krabbe disease and to reVision’s treatment for Stargardt disease.

Krabbe disease is a rare and often life-threatening lysosomal storage disease caused by mutations in the GALC gene, which encodes galactosylceramidase, an enzyme that breaks down galactosylceramide and psychosine. Without adequate levels of galactosylceramidase, psychosine accumulates, causing widespread death of myelin-producing cells and progressive damage to nerves in both the brain and peripheral tissues, eventually resulting in death. Symptoms present by one year of age and median survival ranges from two years of age to five years from onset of symptoms. There are currently no disease-modifying therapies for Krabbe disease.

Passage Bio’s AAV-based gene therapy PBKR03 encodes GALC and is currently in late preclinical development for the treatment of infantile Krabbe disease. In preclinical models, PBKR03 has shown meaningful transduction of both the central and peripheral nervous system, with restoration of myelination in the brain and peripheral nerves. PBKR03 has the potential to treat both the central nervous system and peripheral nerve manifestations observed in Krabbe disease patients.

“Receiving both Orphan Drug and Rare Pediatric Disease designations for PBKR03 underscore the urgent unmet medical need for children with Krabbe disease, for which there are no approved treatments,” said Bruce Goldsmith, president and chief executive officer of Passage Bio. “We are encouraged about the potential of PBKR03 as a life-altering therapy for this underserved patient population, and we look forward to working with the FDA as we solidify our plans to advance PBKR03 into clinical testing in 2021.”

Stargardt disease is also called Stargardt macular dystrophy, juvenile macular degeneration, or fundus flavimaculatus. The disease causes progressive degeneration of the macula, which is an area in the center of the retina that is responsible for sharp, straight-ahead vision. Stargardt disease is one of several genetic disorders that cause macular degeneration. Experts estimate that 1 in 8-10 thousand people have Stargardt disease.

ReVision’s REV-0100 is designed to bind and clear a toxic lipid called lipofuscin. Accumulation of lipofuscin in Stargardt disease leads to cell death and retinal degeneration. REV-0100 has the potential to reduce lipofuscin levels in the retina. There are no other known products in development that remove accumulated lipofuscin through this mechanism of action and no other approved treatment for Stargardt disease.

“FDA’s designation of REV-0100 as an orphan-drug and as a drug for a rare pediatric disease are significant milestones for reVision and underscores the company’s commitment to innovative therapies and treatments for unmet medical needs associated with genetic and progressive vision loss,” said Paul Fehlner, reVision’s president and CEO. “This designation permits reVision to further accelerate the development of our Stargardt disease treatment. Our candidate is based on important discovery research from Weill Cornell Medicine in New York City showing that REV-0100 can reduce levels of toxic lipid material called lipofuscin. reVision is thus poised to demonstrate the benefit of reducing levels of lipofuscin to retinal health in Stargardt disease.”

The FDA grants Orphan Drug designation to drugs and biologics intended for the treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. Orphan Drug designation affords companies the potential for certain benefits, including up to seven years of market exclusivity, assistance in the drug development process, tax credits for clinical development, and exemptions from certain FDA fees.

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes the company eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Sarepta sold its priority review voucher to Vifor Pharma $111 million in February 2020.

The voucher program was due to expire at the end of September but Congress provided a short-term extension of the program. According to the current statutory sunset provisions, after December 11, 2020, FDA may only award a voucher for an approved rare pediatric disease product application if the sponsor has rare pediatric disease designation for the drug, and that designation was granted by December 11, 2020. After December 11, 2022, FDA may not award any rare pediatric disease priority review vouchers.

Going forward, requests for rare pediatric disease designation submitted will be reviewed in a timely manner but the FDA’s previous 60-day response time no longer applies.

Photo: Bruce Goldsmith, president and chief executive officer of Passage Bio

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