Boehringer’s Nerandomilast Advances in IPF Amid Analyst Reservations

Boehringer Ingelheim’s presentation of phase 3 data for its idiopathic pulmonary fibrosis (IPF) drug candidate nerandomilast has received a reserved response from analysts, who described the treatment as “a step forward but not game-changing.”
The company had previously disclosed in September that the study met its primary endpoint, raising expectations for a potential improvement over existing antifibrotic therapies, namely Boehringer’s Ofev and Roche’s Esbriet.

The study enrolled 915 patients, 78% of whom were receiving background antifibrotic treatment—535 on Ofev and 380 on Esbriet. Results showed that at Week 52, patients receiving a high dose of nerandomilast had a mean lung capacity decline of −114.7 ml, compared to −183.5 ml in the placebo group. Among those using Ofev, the decline was −118.5 ml with nerandomilast versus −191.6 ml on placebo. The smallest difference was observed in the subgroup of patients taking Esbriet, where the low dose of nerandomilast performed worse than placebo.
In a note dated May 19, Leerink Partners analysts commented that nerandomilast “looks to us to be an incrementally better Ofev,” but emphasized it remains a disease-slowing rather than disease-halting agent. They characterized it as “a decent Ofev-successor” but noted that its “modest effect size” was unlikely to prompt immediate changes in IPF treatment practices.
Concerns were also raised about the drug’s interactions with current therapies. According to Boehringer, drug-drug interactions between nerandomilast and Esbriet were responsible for the low dose’s failure to improve outcomes in that subgroup. In addition, overlapping toxicity was observed with Ofev. Diarrhea was the most frequently reported adverse event, affecting 41% of patients on the high dose of nerandomilast and occurring most often among those concurrently using Ofev.

Leerink analysts pointed out that this overlap in tolerability could limit the feasibility of using nerandomilast alongside Ofev. “Diarrhea leading to discontinuation was mainly observed with background [Ofev] use, which we think may limit the number of patients who are able to tolerate concurrent use,” they wrote.
While the analysts acknowledged that nerandomilast demonstrated a “solid profile that warrants approval,” they also highlighted the opportunity this leaves for other developers in the IPF space. The perceived limitations of nerandomilast were cited as a positive development for PureTech Health and MannKind, both of which are currently advancing their own IPF programs.