Boehringer Ingelheim established a presence in idiopathic pulmonary fibrosis years ago with a drug that has become a standard treatment for this serious lung disorder. Now the company has the opportunity to bring a different approach to the fatal disease with the first new FDA-approved IPF therapy in more than a decade.
The FDA’s Tuesday regulatory decision for the drug, nerandomilast, covers the treatment of IPF in adults. Germany-based Boehringer, which maintains its U.S. headquarters in Ridgefield, Connecticut, will market the twice-daily pill under the brand name Jascayd.
In IPF, lung tissue becomes thick and stiff. As this tissue leads to permanent scarring called fibrosis, patients find it harder and harder to breath. Shortness of breath and chronic cough are common symptoms. Many IPF patients also experience acute exacerbations, periods when symptoms suddenly intensify. The exact cause of IPF is not known.
The standard of care for IPF includes two older drugs, nintedanib and pirfenidone. Both are oral small molecules, each one designed to block a different protein involved in the formation of fibrotic tissue. The FDA approved the two drugs in 2014. Nintedanib, brand name Ofev, is the product from privately held Boehringer. Neither Ofev nor pirfenidone cures IPF but they can slow its progression.
Jascayd is also not a cure, but it slows IPF progression with a different mechanism of action. This drug, an oral small molecule formulated as a twice-daily pill, is designed to block phosphodiesterase 4B (PDE4B), an enzyme that plays a role in regulating inflammation. Boehringer evaluated Jascayd in two placebo-controlled Phase 3 studies.
The main goal of the studies was measuring the change in forced vital capacity (FVC), how much air a person can exhale after taking a deep breath. Results of the 52-week study showed that patients treated with the study drug had a significantly smaller decline in FVC compared to baseline compared to those given a placebo. The most common side effects reported in during the trial included diarrhea, Covid-19 infection, upper respiratory tract infection, depression, weight loss, and decreased appetite. The Phase 3 results were published in May in the New England Journal of Medicine.
Financial analysts that cover companies developing IPF drugs expected FDA approval for Jascayd given its Phase 3 results. But Leerink Partners’ Faisal Khurshid said in a September note to investors that the Boehringer drug’s contribution to the field is incremental due to “modest efficacy and a complicated story.” Use of the drug on top of existing anti-fibrotic drugs leads to complications — drug-drug interactions with pirfenidone and overlapping diarrhea with Ofev.
“A new therapy for this high unmet need population should nonetheless be accepted by physicians and patients,” Khurshid said.
IPF research has had some notable setbacks. Pliant Therapeutics, which at one time was considered a frontrunner with bexotegrast, discontinued development of the molecule earlier this year after Phase 2b/3 data showed an unfavorable risk/benefit profile.
Other companies remain in the chase, some with new takes on older drugs. Celea Therapeutics spun out of PureTech Health in August with deuperfinidone (formerly LYT-100), a version of pirfenidone with modifications to reduce the adverse effects that limit patient uptake. This oral drug is entering Phase 3 testing. Avalyn Pharma recently raised $100 million for mid-stage testing of its candidates, inhaled versions of pirfenidone and nintedanib intended to offer improved tolerability over the original oral medicines. Last month, United Therapeutics reported that Tyvaso, an inhaled therapy first approved to treat pulmonary arterial hypertension, met the main goal of a Phase 3 test in IPF.
Novel IPF medicines are also in development. Insilico Medicine is conducting a U.S. Phase 2 study evaluating a TNIK inhibitor discovered by the company’s proprietary artificial intelligence technologies. Contineum Therapeutics is proceeding to Phase 2 testing with PIPE-791, a once-daily oral small molecule inhibitor of LPA1, a receptor that contributes to fibrosis.
Photo: Keet / Ullstone picture, via theresy IMAGES
