Merck & Co.’s Winrevair nabs highly-anticipated approval in PAH

2024-03-26

临床3期并购临床结果上市批准优先审批

After Merck & Co. posted data last year showing the extent to which Winrevair (sotatercept-csrk) can boost exercise capacity and prolong survival, the FDA's approval Tuesday of the first-in-class activin signalling inhibitor to treat adults with pulmonary arterial hypertension (PAH) took few by surprise. The outstanding question, however, is how and when the disease-modifying therapy gets incorporated into PAH treatment regimens that haven’t seen a drug with a novel mechanism of action in years.

Winrevair was granted a priority review last year based on data from the 323-patient Phase III STELLAR trial, which showed that when added to background therapy, Winrevair significantly improved exercise capacity as measured by six-minute walk distance (6MWD) at 24 weeks, the primary endpoint. Compared with placebo, the treatment extended the average distance that patients could walk by 40.8 metres.

The drug also demonstrated significant improvements over placebo on eight of nine secondary outcome measures, including an 84% reduction in time to death or first non-fatal clinical worsening event, which sets Winrevair apart from past PAH treatments.

For the first five doses, Winrevair’s label recommends that physicians monitor patient haemoglobin and platelets before administration, and periodically thereafter due to its potential to increase haemoglobin and lead to erythrocytosis, as well as decrease platelet count and lead to severe thrombocytopenia.

Earlier lines down the road

Winrevair, which was specifically cleared to increase exercise capacity, improve functional class, and reduce the risk of clinical worsening events in people with PAH, is given as a shot every three weeks. The treatment works by improving the balance between pro-proliferative and anti-proliferative signalling to modulate vascular proliferation.

“The attraction of sotatercept is that it moves us beyond the three typical pathways where all the other drugs have been developed,” Steven Nathan told FirstWord last year during a call to discuss detailed results from STELLAR.

“Everyone has been looking for something that is perhaps a little bit more upstream because I think we have tapped out the three vasodilatory pathways as much as we can. So, we have been looking for something that attacks the disease a little bit differently and perhaps has more of a chance of being truly disease-modifying,” he added.

Based on the clinical data and mechanism of action, Nathan said at the time that Winrevair could compete with the parenteral prostanoid drug class, as they have “tremendous quality-of-life issues.” He added that Merck’s drug could also end up competing with other approved treatments such as endothelin receptor antagonists (ERAs) and PDE-5 inhibitors PDE-5 inhibitors, which have not demonstrated reversal of PAH.

Ahead of the FDA’s decision, physicians recently interviewed by FirstWord echoed Nathan’s optimism for Winrevair. Results revealed that 35% of physicians said they were extremely enthusiastic about using Winrevair to treat their PAH patients, and 40% described the data from STELLAR as being ‘very’ impressive.

Based on its clinical profile and novelty, the vast majority of physicians anticipate using Winrevair as a second- or third-line treatment option during its first 12 months on the market. However, 13% of those polled said that Merck’s drug would have the biggest impact as an initial therapy for new patients.

Nathan was also bullish on Winrevair’s first-line potential, noting that intuitively, earlier use of the drug should result in greater patient benefits.

“I don't think it is the kind of thing that will be held back waiting for patients who are refractory to all these other treatments. I think it is going to move its way up the chain pretty rapidly if what we saw in the clinical trial bears out in the clinical trenches,” he said.

A win ahead of Keytruda LOE

Tuesday’s approval might also help assuage concerns surrounding Merck’s ability to overcome a potential decline in revenues of blockbuster cancer therapy Keytruda (pembrolizumab) towards the end of this decade – and score a point in the pharma’s favour on its deal-making strategy. For more, see Spotlight On: Merck & Co. continues riding Keytruda wave while scoping horizon for its next dealmaking endeavour.

Winrevair was the key drug in Merck's $11.5-billion acquisition of Acceleron Pharma in 2021. The high price tag was driven, in part, by potential multi-billion-dollar peak sales that could serve as a solid stepping stone into the pharma’s post-Keytruda future.

While Merck has not yet disclosed the price of Winrevair, the Institute for Clinical and Economic Review (ICER) concluded last year that Winrevair would be cost effective for PAH if priced between $18,700 and $36,200 per year. ICER's analysis highlighted the lack of longer-term data, as well as uncertainties about the drug’s effects on mortality and concerns about as-yet-undetected adverse effects.