Gilead, Galapagos’s filgotinib scores in Phase III rheumatoid arthritis trial, but questions remain

Whether the FDA requires completion of a study to look at testicular toxicity before approval could dictate whether the drug launches next year or as late as 2022, an analyst wrote.

Biotech giant Gilead Sciences and a European partner scored a win Thursday with a positive Phase III study of a new drug in rheumatoid arthritis, but analysts say they still have challenges they’ll have to overcome.

Foster City, California-based Gilead and Belgian drugmaker Galapagos announced positive results from the randomized, double-blind, placebo-controlled Phase III FINCH 3 study of filgotinib combined with methotrexate in patients with rheumatoid arthritis who have not yet received methotrexate. The study found that the proportion of patients achieving 20-70 percent improvement in tender or swollen joints was significantly higher after 24 weeks in the experimental group than in the placebo group. The improved response rates held for both the 100mg and 200mg dose groups.

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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.

Gilead’s shares rose 3 percent Friday morning following the news, while Galapagos’s shares were up 25 percent by the early afternoon.

Filgotinib is a JAK inhibitor and in almost neck-and-neck competition against AbbVie’s upadacitinib, which belongs to the same class. AbbVie filed for Food and Drug Administration approval of upadacitinib on Feb. 19. SVB Leerink analyst Geoffrey Porges wrote in a note to investors Friday that FINCH 3 maintained filgotinib’s strong safety profile compared to other JAK inhibitors, including upadacitinib.

Pfizer’s Xeljanz (tofacitinib) is also a JAK inhibitor, already approved for RA, psoriatic arthritis and ulcerative colitis. Another JAK inhibitor, Incyte’s Jakafi (ruxolitinib), is approved for the blood cancers myelofibrosis and polycythemia vera.

One potential concern with filgotinib is the possibility of testicular toxicity in males. In preclinical toxicity models, noted Kemper analyst Anastasia Karpova and others in December 2018, testicular damage causing reduced sperm counts in rats and dogs was observed at doses that produced blood levels of the drug slightly higher than those produced by the 200mg dose. Sperm counts increased after dosing was stopped, but did not return to normal. At the same time, when the animals received doses producing blood levels similar to those produced by the 200mg dose in humans, they did not experience testicular toxicity. To that end, Gilead and Galapagos are conducting MANTA, a randomized, placebo-controlled Phase II study of the drug in men with ulcerative colitis to evaluate testicular safety.

Whether the FDA will require the companies to complete MANTA before it approves the drug, and whether the drug’s potential label will include a warning about male spermatogenesis, remain two key controversies for investors, Porges wrote. If the agency requires it to finish MANTA first, that could push the drug’s launch from 2020 to 2021 or 2022. Other questions he highlighted include whether the FDA approves both doses or, as with other JAK inhibitors, only the lower dose.

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