Boehringer Ingelheim drug FDA approved for the treatment of fatal lung disease IPF
Boehringer Ingelheim discovered the drug for idiopathic pulmonary fibrosis many years ago, which has become the standard treatment for this severe lung disease. Now, the company has the opportunity to bring a different approach to the deadly disease with the first new IPF therapy approved by the FDA in more than a decade.
The FDA’s regulatory decision on the drug nerandomilast on Tuesday covers treatment for adult IPF. Boehringer, based in Germany, is headquartered in Ridgefield, Connecticut, and will sell the twice-daily pills under the Jascayd brand.
In IPF, lung tissue becomes thick and stiff. Because this tissue causes permanent scars (called fibrosis), patients will find it increasingly difficult to breathe. Shortness of breath and chronic cough are common symptoms. Many patients with IPF also experience acute exacerbations, i.e., periods of sudden intensification of symptoms. The exact reason for IPF is not yet known.
The standard of care for IPF includes two older drugs: nidanib and pirfenidone. Both are small oral molecules, each designed to block different proteins involved in the formation of fibrotic tissue. The FDA approved both drugs in 2014. Nintedanib, ofefev, is a product of the privately held Boehringer Ingelheim. Neither Ofev nor pirfenidone cures IPF, but they can slow its progression.
Jascayd is not a cure either, but it slows down IPF progress through different mechanisms of action. The drug is an oral small molecule drug taken twice daily to block phosphodiesterase 4B (PDE4B), an enzyme that plays a role in regulating inflammation. Boehringer Ingelheim evaluated Jascayd in two placebo-controlled phase 3 studies.
The main goal of the study is to measure the change in forceful lung capacity (FVC), the amount of air a person can exhale after taking a deep breath. The 52-week study results showed that patients treated with study medication had a significantly smaller decrease in FVC than those receiving placebo. The most common side effects reported during the trial include diarrhea, Covid-19 infection, upper respiratory tract infection, depression, weight loss, and decreased appetite. The results of the third phase were published in the May New England Journal of Medicine.
Given Jascayd's Phase 3 results, financial analysts covering IPF drug development companies expect the FDA to approve Jascayd. But Leerink Partners' Faisal Khurshid said in a September note to investors that Boehringer Ingelheim's drug contribution to the field is gradual due to “limited efficacy and complex story”. Using this drug on the basis of existing antifibrotic drugs can lead to complications—drug interactions with pirfenidone and overlapping diarrhea with Ofev.
“Nevertheless, doctors and patients should still receive new treatments for this unmet high-needed population,” Cushid said.
IPF research encountered some significant setbacks. Pliant Therapeutics was once considered the leader in Bezoglast, but stopped the development of the molecule earlier this year after the 2b/3rd period data showed adverse risk/benefit status.
Other companies are still chasing, some of which offer new ideas about old drugs. Celea Therapeutics, isolated from PureTech Health in August, introduced deuperfinidone (formerly known as LYT-100), a version of pirfenidone that has been modified to reduce the side effects of limiting patient absorption. This oral drug is entering its third phase of testing. Avalyn Pharma recently raised $100 million for interim testing of its drug candidate, inhaled pirfenidone and nidanib, aiming to provide better tolerance than the original oral medication. Last month, United Therapeutics reported that Tyvaso, the first-ever inhalation therapy approved for the treatment of pulmonary hypertension, met the main goal of the IPF Phase 3 trial.
New IPF drugs are also under development. Insilico Medicine is conducting a Phase 2 study in the United States to evaluate TNIK inhibitors discovered by the company's proprietary artificial intelligence technology. Contineum Therapeutics is undergoing phase 2 testing of PIPE-791, a once-daily oral small molecule inhibitor of LPA1, a receptor that causes fibrosis.
Photo: Kettel/ullstein bild, from Getty Images
