Boehringer, Insilico Make IPF Breakthrough

Recent clinical trial results from Boehringer Ingelheim and Insilico Medicine have shown promising developments in the treatment of idiopathic pulmonary fibrosis (IPF). This lung disease, which primarily affects older adults, is characterized by lung scarring, inflammation, fatigue, and shortness of breath, and typically leads to respiratory failure and death within 3 to 5 years of diagnosis. Both companies reported improvements in lung function, an area where current treatments fall short, but experts remain cautious due to limited data.

Boehringer Ingelheim's Phase III FIBRONEER-IPF trial involved 1,177 patients and tested the drug candidate nerandomilast. The trial showed a significant improvement in forced vital capacity (FVC) at 52 weeks compared to a placebo. This result marks the first IPF Phase III trial in a decade to meet its primary endpoint. However, experts like Allison Reiss from NYU Grossman Long Island School of Medicine are calling for more detailed information regarding the efficacy of nerandomilast across different doses and its performance on secondary endpoints such as time to exacerbation, first hospitalization for respiratory causes, or death.

Reiss is optimistic about the drug’s mechanism of action. Nerandomilast targets the phosphodiesterase 4B (PDE4B) enzyme, potentially reducing inflammation and fibrosis with fewer side effects than drugs targeting multiple enzyme forms. Boehringer plans to release full data and analyses from FIBRONEER-IPF in the first half of 2025.

Insilico Medicine also reported positive results from its smaller Phase IIa trial involving 60 IPF patients. Their drug candidate, ISM001-055, met the primary endpoint of safety and secondary efficacy endpoints, showing a dose-dependent improvement in FVC over 12 weeks. Despite the promising data, Insilico co-CEO Alex Zhavoronkov noted that the study was too small to make definitive claims. Insilico is awaiting results from a parallel Phase IIa trial and plans to conduct a Phase IIb study, pending discussions with regulators.

ISM001-055 was developed using Insilico’s generative AI engine, which analyzed vast amounts of data, including patents, research publications, grants, and clinical trial databases. The drug targets Traf2- and NCK-interacting kinase (TNIK), a protein implicated in both IPF and aging. Zhavoronkov emphasized the importance of finding targets significantly involved in aging due to the prevalence of IPF in older adults.

However, Reiss expressed skepticism about this approach, pointing out that while TNIK is involved in transforming growth factor-β signaling important for IPF, it is predominantly found in the gastrointestinal system. She also highlighted that the study's short duration and small sample size make it difficult to draw concrete conclusions about ISM001-055’s efficacy.

In summary, while the initial results from Boehringer Ingelheim and Insilico Medicine are encouraging, experts agree that more comprehensive data is required to fully assess the efficacy and safety of these new IPF treatments. Both companies are continuing their research and plan to release further data in the coming years.