Boehringer's Phase 3 Lung Fibrosis Trial Achieves Primary Endpoint, Prepares Ofev Successor Filings

Boehringer Ingelheim has announced a significant breakthrough in the treatment of idiopathic pulmonary fibrosis (IPF), ending a long series of failures in the industry. The company reported a successful phase 3 trial for nerandomilast, a potentially first-in-class drug, and outlined plans to seek regulatory approval in the United States and globally.

Current treatment options for IPF include Boehringer’s Ofev and Roche’s Esbriet, which help to manage the condition by slowing the progression of fibrosis. Despite these options, there has been no successful development of drugs that can halt or significantly further slow disease progression. To address this, Boehringer advanced its PDE4B inhibitor, nerandomilast, into a phase 3 clinical trial in 2022.

The results from the phase 3 trial are promising. Patients treated with nerandomilast showed better performance on the forced vital capacity test—a critical measure of lung function—compared to those on a placebo after 52 weeks, achieving the study's primary endpoint. However, Boehringer has not yet disclosed the detailed statistics behind these results, opting instead to present the data in early 2025. This decision leaves some uncertainty about the magnitude of nerandomilast’s effectiveness.

Further information about the trial, such as the performance of different doses and secondary endpoints, including time to adverse events like hospitalization and death, remains undisclosed. Questions also linger regarding how nerandomilast fared in various patient subgroups. The trial included patients who were either on stable therapy with Ofev or Esbriet or had not used either drug for at least eight weeks. This data could elucidate nerandomilast’s effectiveness as an add-on therapy and its potential as a first-line treatment.

Nerandomilast’s unique mechanism of action may provide an edge over existing treatments. Unlike current drugs, it targets PDE4B, an enzyme subtype highly concentrated in the lungs. This may allow nerandomilast to exert anti-inflammatory and antifibrotic effects without the systemic side effects, such as diarrhea and headaches, that have plagued other PDE4 inhibitors. The design of nerandomilast aims to selectively target PDE4B over PDE4D, potentially mitigating these adverse effects. Nonetheless, Boehringer has not yet commented on the drug’s safety and tolerability.

Despite the limited data shared so far, Boehringer’s plans indicate confidence in nerandomilast’s future in IPF treatment. The company intends to seek regulatory approval for the drug in the United States and internationally. Additionally, a second phase 3 trial is underway to evaluate nerandomilast in patients with progressive fibrosing interstitial lung diseases, with primary completion expected in December.

Boehringer’s progress with nerandomilast marks a potential turning point for patients with IPF, offering hope for a more effective treatment option. The forthcoming detailed data will be crucial in assessing the full impact of this new drug.