There are countless nuggets of healthcare gold buried within the almost 1000-page 21st Century Cures Act, signed into law with bipartisan support at the end of 2016.
Among the riches is the Regenerative Medicine Advanced Therapy (RMAT) program, a type of Breakthrough Therapy Designation (BTD) for companies working with cell therapies, therapeutic tissues and the like.
North Carolina-based Humacyte claimed the first RMAT designation on March 20, 2017, for its investigational human acellular vessel (HAV). On Monday, the less than one-year-old rare disease company Enzyvant claimed the second and a BTD to boot.
The compound at hand is RVT-802, a novel biologic therapy Enzyvant licensed from Duke University in a deal announced earlier this year. The initial target is DiGeorge syndrome (DGS), a rare genetic disease that presents with a host of potentially fatal complications such as heart and immune system defects, a cleft palate, low calcium levels in the blood, and delayed development.
Enzyvant expects to file a biologics license application (BLA) in early 2018 for a subset of patients – around one percent – who have what is known as complete DiGeorge Syndrome (cDGS). That equates to a market of just 10-20 children per year in the United States, though the number of indications will ideally expand said CEO Alvin Shih via email.
“We’re doing additional research to understand if there are other potential applications for RVT-802, but our first target is cDGS, where we think the clinical benefit is most clearly demonstrated to date,” Shih said.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Children born with cDGS have a severe lack of thymus tissue, a necessary component of the immune system. With a drastically weakened immune system, they typically succumb to an infection before age two.
Enzyvant’s RMAT-designated therapy is built around a proprietary process for harvesting, culturing, and applying allogeneic (donor) thymic tissue. While it can’t treat the underlying defect in chromosome 22, RVT-802 is designed to restore some of the missing immune function. According to a company statement, preliminary clinical data show a survival rate of over 70 percent for those treated with the therapy.
“The existing data were sufficient as preliminary clinical evidence that RVT-802 may address the medical unmet need in complete DiGeorge syndrome, which is a requirement for both BTD and RMAT,” Shih said.
A lot of that data came through the work of Mary Louise Markert, a professor of pediatrics at Duke who has treated over 70 patients and amassed decades of experience in the field.
Along with addressing an unmet need, the FDA outlines two other basic requirements to be considered for RMAT designation: The product must be in the field of regenerative medicine and it must intend to treat, modify, reverse, or cure a serious or life-threatening disease or condition.
There are substantial rewards for those that are successful. Sponsors of the product become eligible for earlier and more involved interactions with FDA to streamline the development and review process, as happens with other breakthrough therapy designations. RMAT-designated therapies could also qualify for priority review and accelerated marketing approval and a wider scope of evidence may be submitted. That includes real-world clinical evidence, such as patient registries, electronic health records, qualitative data from clinical trials and post-approval monitoring of patients treated with the therapy.
“The RMAT designation is so new, it’s hard to know exactly what to expect,” Shih said. “We know the RMAT designation confers increased interactions with the agency, as well as access to expedited review pathways by the FDA, all in an effort to expedite product development. We look forward to working with the Agency to make this therapy available to patients who need it.”
A subsidiary of Vivek Ramaswamy’s Roivant Sciences group, Enzyvant was formed in July 2016, with support from Plexcera Therapeutics. RVT-802 is one of two drugs in the pipeline, the other is a recombinant human acid ceramidase (rhAC therapy) for Farber disease.
Photo: janulla, Getty Images
