Shares of Paris-based Abivax SA (Paris:ABVX) fell 25.4% to €21 (US$25.07) on March 8 after the company said it would halt a phase IIb/III trial of its lead candidate, ABX-464, in high-risk COVID-19 patients for lack of efficacy.
The decision was based on a data safety monitoring board analysis that Abivax said revealed a "lower than expected rate (10.1%) of progression to severe disease or death with no difference between ABX-464 and placebo groups," each of which also received standard-of-care therapy.
Rationale for the study, miR-age, was bolstered by in vitro data demonstrating that ABX-464 has an apparent antiviral effect on top of the anti-inflammatory activity.
A "robust study design" made the interim readout a reliable guide to futility, said Eric Cua, an infectious disease specialist at the University Hospital Center of Nice, France, and principal coordinator of the study in that country. But while the low rate of severe disease in the high-risk population was unexpected, it also offered "good news about the prognosis of high-risk COVID-19 patients with the current standard of care and with emerging variants," he said.
Disappointed, as chief executives always are in such circumstances, Abivax CEO Hartmut Ehrlich also saw a silver lining in the trial's "good safety and tolerability data," which apparently remained durable despite the study's planned inclusion of high-risk patients with early stage disease. Criteria for the trial called for the enrollment of patients with symptomatic COVID-19, ages 18 and older, with at least one associated risk factor, such as being 65 or older or having diabetes, ischemic heart disease or high blood pressure.
Ehrlich said the outcome would have no impact on the company's broader development of ABX-464, a Rev protein modulator in development for several chronic inflammatory indications. Among them, top-line data are expected this quarter from a phase IIb ulcerative colitis trial and phase IIa rheumatoid arthritis trial.
Cytodyn sets plan for new trial
Shares of Cytodyn Inc. (OTC:CYDY) also fell Monday, declining 28.2% to $2.91 as the company reported summary findings of a phase III trial of its CCR5 antagonist, Vyrologix (leronlimab-PRO 140), in severe to critically ill COVID-19 patients.
Top-line results of the study, summarized by the company, pointed to a 24% reduction in all-cause mortality with leronlimab vs. placebo for invasive mechanical ventilated critically ill patients. The Vancouver, Wash.-based company also cited a shorter average length of hospital stay for patients who received leronlimab in combination with standard of care vs. placebo plus standard of care, and "an improved probability of 'discharged alive' at day 28 (28% versus 11%)."
Some of the conclusions were drawn through the lens of an "’age adjustment' analysis," the company said, performed "as a consequence of an imbalance among enrolled patients over 65 years of age and under 65."
Given the size of the critically ill population on which the reported result was based relative to the phase III trial's overall size – just 16% of the 384 patients enrolled in the study were critically ill – Cytodyn filed an additional protocol with the FDA to support its pursuit of regulatory approvals in the U.S., Canada and U.K.
Nasal vaccines move ahead
Researchers at Rokote Laboratories Finland Ltd., meanwhile, said that within a few months they would start a trial for a nasal spray COVID-19 vaccine they're developing. The new company, based on research carried out at the University of Helsinki and the University of Eastern Finland, was co-founded and supported by both institutions, which are also shareholders in the venture. The first trials of the vaccine will take place in Finland, where there is already commercial technology needed to produce it.
The vaccine candidate uses an adenovirus carrier that contains a cloned DNA strand, which causes nasopharyngeal cells to produce the virus protein which, in turn, produces a response to the vaccine, according to a University of Eastern Finland announcement.
"Vaccines injected intramuscularly produce IgG antibodies in the bloodstream, but nasal vaccines also produce an IgA response that protects mucous membranes. We assume that this can also prevent those who have received the vaccine from transmitting the virus," said company co-founder Seppo Ylä-Herttuala, from the University of Eastern Finland.
Another approach to nasal vaccination is also gaining ground at St. Andrews, Scotland-based Pneumagen Ltd. On Monday, it reported that Neumafil, a carbohydrate-binding molecule it's developing as a pan-viral intranasal drug, was "efficacious, significantly reducing clinical signs and weight loss in animals infected with SARS-CoV-2." The company is now preparing for a phase I trial of the candidate in mid-2021, CEO Douglas Thomson said.