CSL testing coagulation factor blocker in COVID-19 patients; plus vaccine deals and plasma trials
As partnerships aimed at preventing COVID-19 or treating early disease continue to form and expand, CSL has begun testing a blood coagulation factor inhibitor for severe COVID-19.
The CSL Behring unit of CSL Ltd. (ASX:CSL) began a Phase II trial of garadacimab, a mAb against Factor XIIa, to treat severe respiratory distress in COVID-19 patients with pneumonia. The primary endpoint of the double-blind, placebo-controlled trial is the incidence of tracheal intubation or death.
In June, CSL reported that garadacimab met the primary endpoint in a Phase II trial as a prophylactic treatment for hereditary angioedema.
The Coalition for Epidemic Preparedness Innovations (CEPI) said it would grant Sichuan Clover Biopharmaceuticals Inc. $66 million in new funding for preclinical studies, Phase I testing and preparation for efficacy trials of a vaccine candidate. CEPI said in April it would provide $3.5 million to develop the vaccine, SCB-2019.
On June 19, the company began to enroll volunteers in Australia for its Phase I trial of SCB-2019. The study is also evaluating separate adjuvants from GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and Dynavax Technologies Corp. (NASDAQ:DVAX) (see “Clover’s Trial”).
Through separate deals, GSK’s and Dynavax’s adjuvants will also be tested in combination with a vaccine candidate from Medicago Inc. In mid-July, the Quebec City-based company plans to begin Phase I testing of its recombinant Coronavirus Virus-Like Particle (CoVLP) in single and double administration regimens.
Emergent BioSolutions Inc. (NYSE:EBS), the Mount Sinai Health System and ImmunoTek Bio Centers LLC will jointly develop, manufacture and conduct clinical trials of Emergent’s plasma-based COVID-19 hyperimmune globulin product, COVID-HIG.
Mount Sinai and Emergent, which in April received $14.5 million from the U.S. Department of Defense to develop COVID-HIG, will conduct human testing including a post-exposure prophylaxis study. The study, supported by an additional $34.6 million from the DoD, will enroll individuals at high risk of SARS-CoV-2 infection, including front-line healthcare workers and military personnel.
ImmunoTek will extend to Mount Sinai its operating license and knowledge regarding plasma collection for development and manufacturing of COVID-HIG.
For individuals who already have COVID-19, the discontinuation of the first randomized controlled convalescent plasma trial to report data indicates that future studies will need to screen or stratify patients based on baseline titers of neutralizing antibodies (NAbs) against SARS-CoV-2.
The study was led by Erasmus Medical Center researchers and described in a medRxiv preprint posted on July 3. Following baseline NAb detection in most of the patients -- including an imbalance of baseline median NAb titers of 320 on the convalescent plasma group vs. 80 in the standard-of-care cohort -- the trial was halted after discussion with a data safety monitoring board.
The authors wrote that the study, unless redesigned, would be underpowered to detect survival or clinical benefit.
With the caveat of the baseline NAb titer imbalance confounding interpretations, at the time of discontinuation there was no difference between the cohorts in mortality, hospitalization duration or disease severity at day 15.
Separately, Gilead Sciences Inc. (NASDAQ:GILD) has begun randomized, controlled Phase Ia testing of inhaled remdesivir in healthy volunteers ages 18-45. The goal is to bring the antiviral to COVID-19 patients at earlier disease stages in outpatient settings (see “Gilead Goes for Remdesivir Lung Delivery”).