The FDA has approved Boehringer Ingelheim’s nerandomilast as a treatment for idiopathic pulmonary fibrosis (IPF), giving the company a successor to its blockbuster therapy Ofev.
Phosphodiesterase (PDE) 4B inhibitor nerandomilast has been cleared under the Jascayd brand name for the treatment of adults with IPF, with twice-daily oral dosing, after a priority review.
It is the first new therapy for IPF in more than a decade, and it picked up a breakthrough designation from the FDA as it offered a new mechanism of action for the progressive lung disease.
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.
Boehringer’s kinase inhibitor Ofev (nintedanib) is one of the most widely used therapies for IPF, alongside Roche’s kinase inhibitor Esbriet (pirfenidone), and made €3.8 billion in sales for the German pharma group last year. Esbriet was also a €1 billion-plus drug at its peak, but has lost patent protection, and the entry of generics has cut sales below the level they are broken out in Roche’s financial reporting.
With Ofev due to start losing patent protection in around 2029, Jascayd has been approved in time to step into the breach for Boehringer, with a clinical profile that the company says represents an advance in treatment for IPF.
In the FIBRONEER-IPF trial published in the New England Journal of Medicine in May, Jascayd treatment was associated with a slower decline in lung function (measured by forced vital capacity or FVC) than placebo over 52 weeks’ follow-up
Ofev and Esbriet can also slow the decline in lung function in IPF, but are associated with quite a high side-effect burden – particularly gastrointestinal symptoms in the case of Boehringer’s drug – and discontinuation rates for both drugs are high. Diarrhoea was the main side effect with Jascayd in the phase 3 trial, but the rate of discontinuation due to adverse events was similar to placebo.
Boehringer is running a second phase 3 study of the drug called FIBRONEER-ILD in people living with progressive pulmonary fibrosis (PPF), and it has also filed for FDA approval of Jascayd as a treatment for these patients.
Last month, the company reported combined data from the two studies showing a 59% reduction in the risk of death versus placebo in patients who received an 18 mg daily dose of nerandomilast as a monotherapy, which approached but did not quite meet statistical significance.
The FDA has approved with new drug with a broad label, meaning it could find a role as first-line monotherapy either for previously untreated patients or those unable to tolerate other drugs, and also as upfront combination therapy at physician’s discretion, although its label indicates side effect rates rise when used alongside Ofev.
The commercial potential of Jascayd remains somewhat under debate, in part because the improvement on current therapies is viewed by some analysts as fairly modest and not quite strong enough to be practice-changing.
For example, Leerink Partners said earlier this year the drug was “incrementally better” than Ofev, but perhaps not enough to encourage switching early on, adding that the increased rate of side effects like diarrhoea in combination use could hold back the drug.
Pricing and a launch data for Jascayd in the US were not available at the time of writing.
