Novartis snaps up the rights to a Covid-19 antiviral after seeing mid-stage results. So where are the data?
Nearly two months after getting the boot from the NIH’s ACTIV-3 study over a failed futility analysis, Novartis and Molecular Partners are back with mid-stage results they say prove their Covid-19 antiviral works better in patients who aren’t hospitalized — and CEO Vas Narasimhan likes what he sees.
The pharma giant is putting down more than $162 million to in-license ensovibep from Molecular Partners after the candidate met its primary endpoint of viral load reduction over eight days in the first part of a Phase II/III study, the partners announced on Monday.
Molecular Partners’ stock $MOLN got a roughly 20% boost on the news, pricing in at $19.92 on Monday morning.
Michael StumppHowever, the partners have yet to reveal any hard data on the primary endpoint. In fact, the only data point they did report on was a 78% reduction in the risk of Covid-related hospitalization, ER visits and death compared to placebo (a secondary endpoint), which Molecular COO and co-founder Michael Stumpp said was statistically significant. If you take ER visits out of that equation, the antiviral reported an 87% reduced risk in hospitalization and death compared to placebo, CEO Patrick Amstutz said.
A total of 407 non-hospitalized adults with Covid-19 were enrolled in Part A of the Phase II/III EMPATHY study, which tested three different doses of ensovibep (75mg, 225mg and 600mg). In the placebo arm with 99 patients, there were six events (event rate of 6.0%); five patients were hospitalized, two of whom died due to worsening of Covid-19, and one patient had an ER visit only. But only four of 301 patients across the ensovibep arms (1.3%) saw such events, and no patients in the ensovibep arm died, according to Novartis.
Researchers also reported a benefit in time to sustained clinical recovery, another secondary endpoint, which Stumpp said was statistically significant. More data will be presented at a scientific congress later this year, a Novartis spokesperson told Endpoints News.
Ensovibep maintained “potent in vitro pan-variant activity against all variants of concern identified so far, including Omicron,” Novartis said in a statement.
The pharma has chosen to proceed with the lowest dose, 75 mg, and aims to enroll another 1,700 patients in Part B, the Phase III portion of the study. But even without the Phase III data, Narasimhan is already talking about plans to file for an EUA.
“We are now reviewing the topline results from EMPATHY Part A to determine next steps for the development program and a strategy for regulatory submissions to obtain fast-track approvals. Following review of the results, we plan to initiate EMPATHY Part B as quickly as possible, with the lowest effective dose identified in Part A of 75mg,” a spokesperson said.
Novartis was not available for an interview as of press time.
Patrick AmstutzThe company bought into the ensovibep program back in October 2020, putting down $22 million upfront and another $44 million for a chunk of equity. In May, the company launched a Phase II/III trial, sponsored by Molecular Partners, to test the candidate in early-stage Covid patients. Now, Novartis is exercising its option to snap up the rights, which will cost it roughly another $162 million plus “significant royalties” on sales.
“These encouraging results come at a time when the need for therapies with pan-variant activity, such as ensovibep, has never been greater,” Amstutz said in a statement.
It hasn’t been smooth sailing for ensovibep, which was kicked out of the NIH’s ACTIV-3 study back in November after failing a futility analysis in hospitalized Covid-19 patients.
The molecule comes from a class of drugs developed by Molecular Partners that aims to perform the same functions as antibodies with far more target specificity and antiviral protection. Though the DARPin candidate appeared safe, it failed to show efficacy at day 5, when a total of 470 patients were assessed on their need for supplemental oxygen, mechanical ventilation or other supportive care.
“It could very well be, that’s the optimistic part, that in subgroups there is something. But at the same time, it’s such a difficult and heterogeneous setting, that maybe the futility was the right point to say, ‘Let’s rethink, let’s look at the data,” Stumpp said.
