The Rare Disease Day, which takes place at the end of February each year, is designed to focus global attention on the need for therapies to treat patients suffering from devastating rare diseases. The most recent event represented the 13th year it has been held. Over that period, research and development in the area has come a long way, and there are now 420 companies around the world that are active in developing regenerative medicines and advanced therapies for the treatment of rare diseases, according to a new report released by the Alliance for Regenerative Medicine (ARM).
In addition, novel drugs and biologics that have been awarded orphan drug designations are gaining approval. Last year, for example, the FDA’s Center for Drug Evaluation and Research (CDER) reported that 21 of the 48 new medicines that were approved for marketing, were orphan products.
That trend is continuing with several new molecular entities receiving the FDA’s green light this quarter having orphan drug designations. In January, Cambridge, Mass.-based Epizyme Inc. won accelerated FDA clearance for Tazverik (tazemetostat) for the treatment of adults and pediatric patients, 16 and older, with metastatic epithelioid sarcoma not eligible for complete resection.
About a month-and-a-half earlier than expected, Horizon Therapeutics plc won FDA approval for teprotumumab in thyroid eye disease (TED), a progressive autoimmune condition that disproportionately affects women. The drug will be marketed as Tepezza and could generate more than $1 billion in peak annual sales. A rare condition, also known as Graves' eye disease, TED can have significant impact on patients' lives. In many cases, muscles and fatty tissues behind the eye become inflamed, causing the eyes to be pushed forward and bulge outward, a condition called proptosis. That can cause a variety of symptoms such as eye pain, double vision, light sensitivity or difficulty closing the eye.
This month, the agency approved Novartis AG’s Isturisa (osilodrostat), an oral treatment for adults with Cushing’s disease, a rare condition of the adrenal glands. It’s the first FDA-approved 11‐beta‐hyrdoxylase inhibitor that addresses cortisol overproduction and synthesis.
Milan-based Recordati SpA acquired worldwide rights to the drug from Novartis, which received $390 million in the deal. Recordati owes milestone payments for the approval and market access of osilodrostat as well as royalties on sales of the drug. The FDA approval confirmed the orphan status of Isturisa, providing seven years of market exclusivity.
In announcing the decision, Mary Thanh Hai, acting director of the Office of Drug Evaluation II at CDER, said, “The FDA supports the development of safe and effective treatments for rare diseases, and this new therapy can help people with Cushing’s disease, a rare condition where excessive cortisol production puts them at risk for other medical issues.”
It is likely that more new medicines targeting rare diseases will be reaching the market in the not too distant future, with the ARM report identifying 42 late-stage studies among the 647 ongoing rare disease clinical trials utilizing regenerative medicine technologies. Among them is Valrox (valoctocogene roxaparvovec) from San Rafael Calif-based Biomarin Pharmaceutical Inc., which is poised to reshape the treatment landscape for hemophilia A. The therapy, which also has orphan drug designation, has moved one step closer to entering the U.S. market, with the company reporting that that the FDA had accepted for priority review the BLA for its investigational AAV5 gene therapy for adults with hemophilia A, setting a PDUFA action date of Aug. 21, 2020. The application is based on a phase III interim analysis of study participants treated with investigational product and three-year phase I/II data.
In its year-end financial report, Bluebird Bio Inc. reported that it had initiated a rolling BLA submission of Lentiglobin for beta-thalassemia for FDA approval. It added it is engaged in discussions with the agency on the requirements and timing of certain information to be provided in the application and the company expects the BLA submission to be completed in the second half of the year.
The ARM report notes the importance of regenerative medicines targeting rare diseases is catalyzing an increasing number of deals. Notable in 2019 was Voyager Therapeutics Inc., which attracted two significant deals. One new partner, Neurocrine Biosciences Inc., agreed to pay the company $165 million up front and earmarked $1.7 billion for future milestone payments for the rights to develop and commercialize four experimental adeno-associated virus-based gene therapies, beginning with one for Parkinson's disease and another for Friedreich's ataxia.
Voyager also signed a second deal with Abbvie Inc. involving Parkinson's disease. North Chicago-based Abbvie paid $65 million up front in exchange for an exclusive option to license vectorized antibodies targeting misfolded alpha-synuclein proteins for synucleinopathies. The agreement builds on a similar Alzheimer's disease deal they inked in 2018.
The steady deal flow last year has continued. Today, Redwood City, Calif.-based Codexis Inc. reported it had signed a strategic collaboration and license agreement with Takeda Pharmaceutical Co. Ltd. for the research and development of novel gene therapies for certain disease indications, including the treatment of lysosomal storage disorders and blood factor deficiencies.
Using its Codeevolver protein engineering platform, Codexis will generate gene sequences encoding protein variants tailored to enhance efficacy as a result of increased activity, stability and cellular uptake, and Takeda will combine those transgenes with its gene therapy capabilities to generate drug candidates for the treatment of rare genetic disorders. It will also be responsible for the preclinical and clinical development and commercialization of gene therapy products resulting from the collaboration programs. In addition to three initial programs, Takeda may initiate up to four additional programs for separate target indications. In return, Codexis is eligible to receive an up-front payment, reimbursement for research and development fees, development and commercial milestone payments, and low- to mid-single-digit percentage royalties on sales of any commercial product developed.
…as does cash
ARM reported that 2019 was the second highest year on record for venture financing for rare disease in the regenerative medicine sector, raising in excess of $1.5 billion. The haul was part of a $6.4 billion total raised by public and private companies involved in regenerative medicines for treating rare diseases. One of the leading public offerings involved gene editing pioneer Crispr Therapeutics AG, which priced its public offering of 4.25 million shares at $64.50, grossing the company $274.1 million.