The next few months could bring the first gene therapy for hemophilia, a new type of multiple myeloma drug and an additional treatment option for a devastating muscular condition.
The Food and Drug Administration is set to make decisions on approval of all three, as well as on a closely watched arthritis pill and the first oral drug for spinal muscular atrophy, between July and September.
A regulatory OK for Roctavian, BioMarin Pharmaceutical's experimental hemophilia A treatment, would be a particularly significant milestone — the first gene therapy for one of the world's most well-known inherited diseases. Approvals for Roche's risdiplam, NS Pharma's viltolarsen, Gilead's filgotinib and GlaxoSmithKline's belantamab mafodotin would also be notable.
The list of experimental drugs slated for the FDA's review during the third quarter was originally longer, but the agency cleared three targeted cancer therapies months ahead of schedule. (Seattle Genetics' Tukysa, Novartis' Tabrecta and Eli Lilly's Retevmo were all approved in April and May.)
Even as it's moved quickly to approve new drugs, the FDA has acknowledged the strain resulting from the work the agency is doing to oversee COVID-19 vaccine and drug development. So far, new drug reviews haven't been heavily affected, but the FDA has warned they could be slowed.
The five experimental drugs are listed in order of the currently scheduled date by which the FDA has agreed to make a decision on approval.
GlaxoSmithKline's belantamab mafodotin for multiple myeloma
Around a dozen drugmakers are developing multiple myeloma treatments that target a protein known as BCMA, which is found on nearly all malignant cells. GlaxoSmithKline looks to be in a position to get there first.
GSK's drug, called belantamab mafodotin, is an antibody-drug conjugate, designed to bind to the BCMA target and deliver a small chemotherapy payload to attack cancerous cells. The conjugate approach is employed by Seattle Genetics' Adcetris and Roche's Kadcyla for other types of blood cancer.
Behind belantamab mafodotin, however, several other BCMA-targeting therapies are nearing key milestones, including a CAR-T cell therapy from Bristol-Myers Squibb and Bluebird bio, as well as a bispecific antibody from Regeneron.
They would trail belantamab mafadotin if the GSK drug is approved by the FDA's target decision date sometime this month. But the rival therapies could potentially offer advantages in greater effectiveness or more manageable side effects. Notably, balantamab mafadotin is associated with an eye-related side effect called keratopathy.
NS Pharma's viltolarsen for Duchenne muscular dystrophy
The FDA's decision to approve Sarepta Therapeutics' Exondys 51 for Duchenne muscular dystrophy in 2016 was one of the most controversial in the agency's recent history. The drug, a type of genetic treatment known as "exon-skipping," was the first specifically cleared for patients with DMD.
Approval late last year of Sarepta's second drug — Vyondys 53 for a different segment of DMD patients — was nearly as dramatic, with the FDA reversing an initial rejection after the company appealed to more senior agency officials.
The FDA's review of a DMD treatment developed by NS Pharma, a little-known subsidiary of Japan's Nippon Shinyaku, promises to be less eventful.
NS' drug, called viltolarsen and designed to treat the same group of DMD patients as Vyondys 53, works similarly to both of Sarepta's drugs. Study results published in JAMA Neurology this past May suggest it might even work better than Vyondys 53, although comparing drugs across trials can be misleading.
Like Sarepta, however, NS is offering the FDA limited evidence to go on. The study supporting the drugmaker's application primarily tested whether viltolarsen increased the production of a key protein that's largely missing in children with DMD and, notably, lacked a placebo comparison.
Having cleared Exondys 51 and then Vyondys 53, however, the FDA seems to have signaled it will accept early data as compelling enough to merit approval. A decision is expected sometime in August.
Gilead's filgotinib for rheumatoid arthritis
For Gilead and partner drugmaker Galapagos, much is riding on filgotinib. The drug is at the center of a research collaboration between the two companies, first inked in 2015 and then expanded with a $5.1 billion pact last year.
Part of a class of drugs called JAK inhibitors, filgotinib is aimed first at rheumatoid arthritis, a chronic condition for which it will have much competition. Three other JAK inhibitors, Pfizer's Xeljanz, Eli Lilly's Olumiant and AbbVie's Rinvoq, are already approved for rheumatoid arthritis, which is also commonly treated with biologic drugs like Humira.
Some analysts on Wall Street see filgotinib as safer than its JAK-blocking rivals, but the FDA appears to be viewing the risk of blood clots as characteristic of the drug class.
Gilead and Galapagos still think filgotinib can stand out and are counting on an August approval from the FDA to prove it. Clearance for rheumatoid arthritis would be the first step in proving the drug's future for other inflammatory conditions, like Crohn's disease, uveitis and psoriatic arthritis.
BioMarin's Roctavian for hemophilia A
An approval for BioMarin's Roctavian would be a significant moment for the still-emerging gene therapy field. The experimental hemophilia A treatment wouldn't be the first gene therapy to gain FDA clearance — that milestone went to Luxturna for an inherited form of blindness — but it would offer thousands of patients long-lasting control of a disruptive and damaging bleeding disorder.
Roctavian also typifies the substantial benefits gene therapy can offer. Studies showed the treatment largely eliminated bleeding episodes, enabling patients to drastically reduce how much they rely on expensive factor replacement therapy that aids blood clotting. Years later, patients who received the treatment are still largely free of both.
BioMarin has suggested a price for Roctavian as high as $3 million, arguing the drug's value is clear when factor replacement therapy can sometimes cost as much as $1 million per year for severe hemophilia patients.
The company recently detailed follow-up data up to four years post-treatment in patients who were enrolled in early clinical trials. While their levels of blood clotting activity appear to decline over time, they are all still producing the Factor VIII protein that's reduced or missing in patients with hemophilia.
Roche's risdiplam for spinal muscular atrophy
Spinal muscular atrophy, or SMA, is an often-fatal neuromuscular condition that primarily affects infants and children. Until three and a half years ago, there was no treatment.
An approval for Roche and PTC Therapeutics' risdiplam, expected by August 24, would bring to market the third treatment for the disease and the first one taken orally, which may be more convenient for some patients.
The companies have played up risdiplam's advantages compared to Spinraza, the first SMA drug, as well as versus Novartis' gene therapy Zolgensma. Spinraza is administered via a spinal injection, while Zolgensma is infused intravenously for treating infants.
Roche and PTC sought to submit to the FDA study data covering a broad range of patients, from infants to adults and across various levels of disease severity. In doing so, however, they caused the agency to extend its approval review by three months in order to take into account results from a study in less severe adolescents and adults.