COVID-19 Hits and Misses: CureVac/GSK and Rigel

As the COVID-19 pandemic continues with surges in the U.S. in unvaccinated people, biopharma companies are still working on new vaccines and therapies against the disease. Here’s a look at two recent stories.

CureVac and GSK’s COVID-19 Vaccines Show Promise in Preclinical Studies

CureVac and GlaxoSmithKline published preclinical data on CureVac’s first-generation vaccine candidate, CVnCoV, and second-generation vaccine candidate, CV2CoV. The vaccines were investigated in a SARS-CoV-2 challenge in non-human primates. This means the cynomolgus macaques received one of the vaccines, their immune responses analyzed, then injected with the COVID-19 virus.

CV2CoV, the second-generation vaccine, demonstrated better activation of innate and adaptive immune responses, with stronger memory B and T-cell activation compared to the first-generation vaccine, CVnCoV. The second-generation candidate also showed higher antibody neutralizing abilities against chosen viral variants, including Beta, Delta and Lambda. The data has been uploaded to the preprint server bioRxiv.

The second-generation vaccine uses CureVac’s mRNA backbone, which it is developing with GSK. It is made up of a non-chemically modified mRNA and encodes for the prefusion stabilized full-length spike protein of SARS-CoV-2 and formulated within Lipid Nanoparticles (LNPs).

“In this animal model, CV2CoV is shown to induce broad antibody and cellular immune responses very similar to the breadth of the immune responses observed after infection with SARS-CoV-2,” said Igor Splawski, CureVac’s chief scientific officer. “The current study shows that the immune responses and resulting protection produced by our second-generation candidate, based on our mRNA technology featuring targeted optimizations, are substantially improved in non-human primates against both the original SARS-COV-2 virus as well as the Beta and Delta Variants of Concern and the Lambda Variant of Interest.”

They expect to start a Phase I clinical trial in the fourth quarter.

FDA Rejects Rigel’s EUA Submission for Fostamatinib for COVID-19

The U.S. Food and Drug Administration (FDA) told Rigel Pharmaceuticals that the data it submitted in late May for Emergency Use Authorization (EUA) for fostamatinib for hospitalized COVID-19 patients was insufficient at this time. This was based on data from a NIH/NHLBI-sponsored Phase II trial. The agency indicated it was committed to working with the company to develop the drug, which is currently being investigated in a Phase III trial.

“With new virus variants spreading and vaccination rates plateauing, there remains a need for therapies that can improve outcomes for hospitalized patients, particularly patients suffering from hyperinflammatory COVID-19-related complications,” said Raul Rodriguez, president and chief executive officer of Rigel. “The Rigel team continues to focus on enrolling our Phase III clinical trial, which we anticipate completing later this year, and we look forward to providing further safety and efficacy data from this larger, 308-patient trial of fostamatinib in COVID-19 patients. If this trial meets its endpoints, we plan to resubmit our EUA application with this additional data.”

Fostamatinib is approved under the brand name Tavalisse to treat adults with chronic immune thrombocytopenia in patients who did not respond to a previous treatment. It is an oral spleen tyrosine kinase (SYK) inhibitor. Although SARS-COV-2 primarily infects the upper and lower respiratory tract, leading to acute respiratory distress syndrome (ARDS), some patients undergo organ damage including myocardial injury, acute kidney injury, shock that causes endothelial dysfunction and micro and macrovascular thrombosis. Much of the pathology of the virus appears to be secondary to a hyperinflammatory immune responses that is tied to increased risk of thrombosis.

SYK is involved in the intracellular signaling pathways for a number of different immune cells. Inhibiting SYK is believed to improve COVID-19 by inhibiting key Fc gamma receptors and c-type lectin receptor (CLR) mediated drivers of pro-inflammatory cytokine release by a variety of immune cells.