Covid-19 roundup: Novartis treatment comes up short in PhIII; Humanigen expands trial, but draws criticism

A major player trying to adapt an anti-inflammatory for Covid-19 has seen the drug fall flat.

Novartis reported Friday that a Phase III trial evaluating canakinumab in hospitalized Covid-19 cases with pneumonia and cytokine release syndrome did not meet its primary endpoint. The interim analysis showed that the drug did not improve the chance of survival without the need for ventilators compared to the control group.

Additionally, the study failed to meet the secondary endpoint of reducing mortality rates after four weeks of stopping treatment.

“Though the…trial did not show the patient benefit we were hoping for, it helps improve the scientific understanding of COVID-19 and the role of interleukin-1β inhibition,” Novartis CMO John Tsai said in a statement.

Researchers studied canakinumab on top of standard of care against the standard of care with placebo. For the primary, canakinumab demonstrated 88.8% survival without ventilation compared to 85.7% in the control, good for a p-value of 0.29. In the secondary, the mortality rate in the drug arm was 4.9% against 7.2% for placebo, giving a 0.33 p-value. There were no new safety issues.

Canakinumab was first approved in 2009 and is sold under the brand name Ilaris. An IL-1 beta inhibitor, the drug is indicated in several rare conditions, including periodic fever syndromes, adult-onset Still’s disease and systemic juvenile idiopathic arthritis.

The landscape for Covid-19 treatments is scarce, with only one therapy currently fully approved by the FDA — Gilead’s Veklury. That drug, also known as remdesivir, was given the green light despite a large WHO-backed study saying it had little to no effect in shortening hospital stays, improving mortality rates or reducing the number of patients needing ventilators.

Regeneron and Eli Lilly are working on their own Covid-19 treatments as well, and Novartis continues to study ruxolitinib in the disease with results from a Phase III expected by the end of the year.

Former Shkreli outlet Humanigen releases positive interpretation of blinded data after DSMB recommends trial expansion

Humanigen, one of “Pharma Bro” Martin Shkreli’s former companies, also spotlighted results from a Covid-19 treatment study for their experimental drug lenzilumab.

However, concerns arose from outside analysts about the nature of how Humanigen $HGEN arrived at its results. According to a report from STAT News, two experts in clinical trial statistics said that Humanigen’s disclosure of the results is not appropriate given that the company has not actually seen any of the data.

Humanigen is conducting an “adaptive trial,” which allows a study to be expanded at a certain point should the DSMB recommend it do so. In this instance, the DSMB recommended the trial expand from 257 expected improvements to 402, and Humanigen reverse-engineered that recommendation to estimate that the lenzilumab arm of the trial resulted in 37% more recoveries.

“Adaptive trials are designed to keep this kind of information away from the sponsor and, in particular, away from the public and releasing it in this fashion can cause operational bias and jeopardize the integrity of the study,” Kert Viele, director of modeling and simulation at top firm Berry Consultants, told STAT.

Viele added that releasing such an interpretation could put regulatory approvals at risk. Humanigen said it expects to apply for a EUA in the first quarter of next year.

Despite the results, investors seemed excited at the news. Humanigen’s stock price shot up about 10% in early Friday trading.

Lenzilumab, a GM-CSF monoclonal antibody, is being studied to treat overactive immune responses seen in graft-versus-host disease and CAR-T cancer therapies. Back in 2015, Shkreli and an investment group bought a majority stake in the company, then known as KaloBios. When Shkreli was arrested for securities fraud, KaloBios fired him, declared bankruptcy and re-emerged as Humanigen in 2016.

Aspirin to be studied in UK’s large RECOVERY trial

A common over-the-counter drug is now being studied to treat Covid-19 cases.

UK researchers are looking at whether or not Aspirin can reduce the risk of blood clots in individuals with Covid-19. The drug, an anti-inflammatory and blood thinner, will be included in the large RECOVERY trial evaluating several potential Covid-19 treatments, the scientists said Friday.

More than 2,000 patients are expected to receive a daily 150 mg Aspirin pill as part of the study, on top of the standard of care. The results will be compared to the standard of care alone, and researchers will be looking at whether the drug improves mortality rates after four weeks.

The rationale for adding the drug to the trial stems from overactive platelet activity in those with the disease, leading to a higher risk of clots.

“We felt it was particularly important to add aspirin to the trial since there is a clear rationale for believing that it might be beneficial and it is safe, inexpensive and widely available,” said Peter Horby, co-chief of RECOVERY, in a statement. “We are looking for medicines for COVID-19 that can be used immediately by anyone, anywhere in the world. We do not know if aspirin is such a medicine but we will find out.”

Researchers cautioned that it may take several months to know if Aspirin has any substantial effect in treating Covid-19. The other drugs in the study are Azithromycin, Tocilizumab, convalescent plasma and Regeneron’s experimental antibody cocktail.

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