Clinical trial results shared by Boehringer Ingelheim and Insilico Medicine showed improvement in idiopathic pulmonary fibrosis, an intractable lung disease for which current treatment options fail to stop progression, but the data were limited, leaving experts wanting.
Patients with idiopathic pulmonary fibrosis got a double helping of good news in the clinical trials arena last week as Boehringer Ingelheim and Insilico Medicine each reported positive data from their respective trials.
The results indicate that both companies’ idiopathic pulmonary fibrosis (IPF) drug candidates might be able to stop or reverse decline in lung function—something no current treatments can offer. But experts cautioned that the data drops were light on the details and that more information is needed before either asset can be accurately evaluated.
A progressive interstitial lung disease disproportionately affecting older adults, IPF is characterized by lung scarring, inflammation, fatigue and shortness of breath. It ultimately leads to respiratory failure and death within 3–5 years of diagnosis. As its name suggests, the origin of IPF is unknown.
“IPF is a very complex, multifactorial and very idiopathic process,” Insilico co-CEO Alex Zhavoronkov told BioSpace.
There is no cure for IPF and current treatment is designed to minimize symptoms, maintain quality-of-life and slow progression, Allison Reiss, an associate professor at NYU Grossman Long Island School of Medicine, told BioSpace in an email. She added that “mainstay treatment” consists of Boehringer’s Ofev (nintedanib) and Roche’s Esbriet (pirfenidone), both antifibrotic drugs, along with pulmonary rehabilitation.
However, Zhavoronkov said, “neither of these drugs are extremely well tolerated,” and they only slow down decline in forced vital capacity (FVC), a key measure of lung function in IPF. “Usually, you see the decline on the standard of care.”
Insilico, Boehringer See Improvements in Key IPF Indicator
On Sept. 16, Boehringer reported that its IPF drug candidate nerandomilast elicited a significant improvement in FVC at 52 weeks versus placebo in the Phase III FIBRONEER-IPF trial of 1,177 patients. FIBRONEER-IPF “is the first IPF Phase III trial in a decade to meet its primary endpoint,” Ioannis Sapountzis, Boehringer’s head of global therapeutic areas, said in a statement.
Reiss said she would like further specifics in regard to that endpoint. “[Boehringer Ingelheim] said [the study] met the endpoint, which means that those on the drug performed better on the forced vital capacity test, but on both doses or one of the doses? And how much better?” Trial participants were given either 9 mg or 18 mg of nerandomilast twice a day or a placebo for at least 52 weeks.
Additionally, Reiss is seeking more information on the secondary endpoints: time to an IPF exacerbation, first hospitalization for respiratory cause, or death. She noted, however, that nerandomilast’s mechanism of action is promising. By preferentially blocking the phosphodiesterase 4B enzyme, she explained, “PDE4B inhibitors interfere with the function of a very specific form of the phosphodiesterase enzyme so that this class of drugs may be able to reduce inflammation and fibrosis in IPF with less side effects than a drug that would inhibit multiple forms of the enzyme.”
In an emailed statement, a Boehringer spokesperson told BioSpace the company has a strong focus on IPF, given the high unmet need. The company plans to present full data and analyses from FIBRONEER-IPF in the first half of 2025.
Insilico, meanwhile, reported similarly positive results on its much smaller Phase IIa trial of 60 patients with IPF. Specifically, the company released results the day after Boehringer showing that its ISM001-055 met the primary endpoint of safety and secondary efficacy endpoints, demonstrating a dose-dependent improvement in FVC over 12 weeks.
Zhavoronkov acknowledged that the study is “not powered enough for me to go out and make super big claims . . . but when you see the chart, it’s very clear that you see that the drug is working.”
Insilico is currently awaiting the results of a second, parallel Phase IIa trial. Next, Zhavoronkov said the company expects to run a Phase IIb study but added that the team wants to meet with regulators to understand the regulatory pathway. He suggested there could be potential for the candidate to be fast-tracked. “If you see the improvements in forced vital capacity, and it’s strong enough evidence to convince the regulators, maybe patients should be on the drug right now,” he told BioSpace.
ISM001-055—which was wholly designed using Insilico’s generative AI engine referencing millions of data files, including patents, research publications, grants and clinical trial databases—targets Traf2- and NCK- interacting kinase (TNIK). Zhavoronkov explained that, due to the prevalence of IPF in people 65 years and older, Insilico was looking for targets that were also “very strongly implicated” in aging, Zhavoronkov said. “We were looking for a dual-purpose target.” TNIK scored high in six hallmarks of aging, and there was significant overlap in hallmarks of IPF, he said.
However, Reiss said she is “pretty skeptical” about the approach. She noted that while TNIK is present in the lungs and “does regulate transforming growth factor-β signaling, which is important in IPF,” it is mostly found in the gastrointestinal system.
Reiss added that the duration of the study was too short and the number of subjects was too small to draw any conclusions about ISM001-055’s efficacy.
“[We’ll] have to wait and see,” she said.
