Boehringer Ingelheim’s long-awaited phase 3 lung disease data received a muted reception from analysts who labeled nerandomilast “a step forward but not game-changing.”
Boehringer revealed the study, which tested the PDE4B inhibitor in idiopathic pulmonary fibrosis (IPF), met its primary endpoint in September. The update ended the long wait for a molecule capable of improving on Boehringer’s Ofev and Roche’s Esbriet but left questions unanswered. Boehringer filled in the gaps in a presentation at the American Thoracic Society and a paper in The New England Journal of Medicine.
The paper showed that 78% of the 915 people in the phase 3 trial took background antifibrotic therapy, with 535 on Ofev and 380 using Esbriet. Across the entire population, mean changes on a measure of lung capacity at Week 52 were −114.7 ml on the high dose of nerandomilast and −183.5 ml on placebo.
Among people taking Ofev, the figures were −118.5 ml on nerandomilast and −191.6 ml on placebo. The gap was smallest in the subgroup of patients on background Esbriet. In that subgroup, the low dose of the study drug performed worse than placebo.
Leerink Partners analysts said in a May 19 note to investors that nerandomilast “looks to us to be an incrementally better Ofev, but in essence it is still disease-slowing rather than disease-halting.” Calling nerandomilast “a decent Ofev-successor,” the analysts said the drug candidate’s “modest effect size” on lung function “is not likely to encourage an immediate change in IPF treatment.”
The use of nerandomilast is complicated by drug-drug interactions with Esbriet and overlapping toxicity with Ofev, the analysts said. Boehringer said the drug-drug interactions caused the lower dose of nerandomilast to fail to improve outcomes when combined with Esbriet. Diarrhea, which was reported in 41% of people on the high dose of nerandomilast, was most common in people also taking Ofev.
“There may be an overlapping tolerability issue with background [Ofev],” the analysts said. “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 of both nerandomilast and [Ofev].”
The analysts said the trial found nerandomilast has a solid profile that warrants approval. However, the mix of the “modest” effect on lung function and concerns about combinations mean the analysts still see opportunities for other companies. The analysts said the limitations of nerandomilast are positive for PureTech Health and MannKind, both of which have IPF programs in the clinic.