Trial sets up filings for Boehringer IPF drug nerandomilast

With new phase 3 data in hand, Boehringer Ingelheim is preparing to file for approval of nerandomilast, a would-be successor to its blockbuster idiopathic pulmonary fibrosis (IPF) therapy Ofev.

Headline results from the FIBRONEER-IPF study showed that nerandolimast was able to achieve an improvement from baseline in forced vital capacity – a key measure of lung function – compared to placebo after 52 weeks of treatment.

According to the German pharma group, the results should be enough to form the basis of regulatory filings for nerandomilast – an oral PDE 4B inhibitor with a breakthrough designation from the FDA – in the US and other regions of the world next year.

At the same time, it is running a second phase 3 study of the drug called FIBRONEER-ILD in people living with progressive pulmonary fibrosis (PPF).

Ioannis Sapountzis, head of global therapeutic areas at Boehringer, said that FIBRONEER-IPF is the largest trial in IPF conducted to date, involving 1,177 patients in more than 30 countries, and is "the first IPF phase 3 trial in a decade to meet its primary endpoint."

In IPF, the lungs become increasingly damaged by scar tissue, resulting in breathing getting progressively more difficult, and it is generally considered a terminal illness despite the availability of drug treatments. It has an average survival time of only three to five years from diagnosis.

One of the top drugs for the disease is Ofev (nintedanib), a kinase inhibitor that has been approved for around a decade for IPF and is also used to treat other respiratory disease characterised by fibrosis, including interstitial lung disease associated with systemic sclerosis or scleroderma (SSc-ILD).

Its main rival is Roche's kinase inhibitor Esbriet (pirfenidone), a €1 billion-a-year drug at its peak that is now facing generic competition and saw sales slump to around €214 million last year.

Ofev and Esbriet can both slow the decline in lung function in IPF, but are associated with quite a high side-effect burden. Ofev, for example, causes gastrointestinal symptoms like diarrhoea, nausea, and stomach pain in around two-thirds of patients, and discontinuation rates for both drugs are high.

Nerandomilast (BI 1015550) has been highlighted for some time as Boehringer's best chance to defend its IPF business in the coming years. Ofev contributed €3.5 billion of the company's total revenues of €25.6 billion last year, but will start losing market exclusivity later this decade.

The full efficacy and safety data from the study isn't expected to be presented until next year so – for now – the potential of the new drug remains up in the air. A key secondary endpoint is the time to an IPF exacerbation, hospitalisation for breathing problems, or death, which if positive could differentiate the drug from current therapies.

Boehringer has previously said it has the potential to address both scarring of lung tissue and inflammation associated with pulmonary fibrosis.