WHO data show quartet of therapies fail to reduce COVID death
Gilead’s Veklury among repurposed therapies missing mark in SOLIDARITY
Data from WHO’s SOLIDARITY trial reiterate the results of NIH’s ACTT: Veklury does not provide a survival benefit in COVID-19.
The interim results from WHO’s open-label master protocol trial, published Thursday in medRxiv, showed that Veklury remdesivir from Gilead Sciences Inc. (NASDAQ:GILD) failed to reduce 28-day mortality in hospitalized COVID-19 patients, missing the primary endpoint.
The data came as Sinopharm and partners Sanofi (Euronext:SAN; NASDAQ:SNY) and Translate Bio Inc. (NASDAQ:TBIO) delivered data for their COVID vaccine programs.
A trio of other therapies also failed in SOLIDARITY: lopinavir-ritonavir, which had also missed the primary endpoint of lowering 28-day mortality in the U.K. RECOVERY trial; lopinavir-ritonavir plus IFNB1; and, as previously reported, hydroxychloroquine.
None of the repurposed drugs in the trial’s four arms reduced initiation of ventilation or hospitalization duration.
In a statement on the readout, Gilead contrasted SOLIDARITY’s design with that of the double-blind Phase III ACTT study, which also evaluated hospitalized COVID-19 patients. The company said that because SOLIDARITY’s “design prioritized broad access, resulting in significant heterogeneity in trial adoption, implementation, controls and patient populations,” it is unclear whether firm conclusions can be made based on the study’s results.
Still, like SOLIDARITY’s readout, final data from ACTT showed that Veklury failed to lower the 28-day mortality rate, a secondary endpoint. Data were reported last week in The New England Journal of Medicine.
In May, interim data from the study, which supported FDA’s emergency use authorization of the antiviral, also did not show a statistically significant survival benefit at 14 days. It did meet ACTT’s primary endpoint of shortening time to recovery, which was defined as hospital discharge or hospitalization only for infection control.
Clinical, preclinical vaccine readouts
China National Pharmaceutical Group Corp. (Sinopharm) reported Phase I/II data showing BBIBP-CorV is immunogenic in non-elderly adults and those ages 60 and up, although the inactivated SARS-CoV-2 vaccine was less potent in the older population.
In the study’s Phase I portion, prime-boost administration of 2, 4 and 8 μg of the vaccine given 15 days apart resulted in dose-dependently neutralizing geometric mean titers (GMTs) of 87.7-228.7 in adults ages 18-59; and 80.7-170.9 in the elderly cohort. Part I enrolled 96 volunteers in each age group.
In the Phase II portion, volunteers ages 18-59 who received prime-boost administration of the middle dose 14, 21 or 28 days apart produced neutralizing titers of 169.5, 282.7 and 218, respectively.
Both portions of the trial were placebo-controlled. All placebo recipients had no detectable neutralizing antibodies; and none of the participants in the Chinese study who received BBIBP-CorV experienced grade 3 or worse adverse events within seven days of administration. Data were reported in The Lancet Infectious Diseases.
In August, Sinopharm reported in The Journal of the American Medical Association interim Phase I data for a different inactivated SARS-CoV-2 vaccine, which was also immunogenic and well tolerated. One week later, the state-affiliated Global Times reported that China has been offering citizens a COVID-19 vaccine from Sinopharm since July 22.
Separately, Sanofi (Euronext:SAN; NASDAQ:SNY) and Translate Bio Inc. (NASDAQ:TBIO) said they plan to begin Phase I/II testing of mRNA vaccine MRT5500 this quarter. The announcement came alongside publication of data in bioRxiv showing the COVID-19 vaccine is immunogenic in Cynomolgus macaques.
Prime-boost administration of low, medium and high doses induced dose-dependent neutralizing GMTs at day 35 of 555, 719 and 1,877 in a microneutralization assay; and GMTs of 924, 961 and 2,971 in a pseudovirus neutralization assay. The microneutralization and pseudovirus GMTs in a panel of 93 convalescent sera samples were about 60 and 70, respectively.
The vaccine was also immunogenic in mice, and led to Th1-biased T cell responses in both animals.
IFNB1 – Interferon β