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Invivyd, Inc announced that it has formed a best-in-class clinical and translational study group, the (Spike Protein Elimination and Recovery) SPEAR Study Group, with leading investigators focused on the biology and clinical disease or injury associated with chronic exposure to SARS-CoV-2 virus or mRNA vaccine-mediated spike protein.
The SPEAR Study Group will structure and guide anticipated clinical trials evaluating the effects of broadly neutralizing anti-SARS-CoV-2 spike protein monoclonal antibody (mAb) therapy in people suffering from Long Covid or Post-Vaccination Syndrome (PVS), conditions believed to be mediated by persistent viral reservoirs or circulating spike protein. Persistent SARS-CoV-2 spike protein has been identified in both populations, and both populations have overlapping manifestations of apparent clinical disease. As many as 5% or more of Americans have reported recent long Covid symptoms, an extraordinary medical burden that will continue to evolve as infections continue in the US.
The SPEAR Study Group was initiated in response to a growing number of case reports and reported case series from across the US suggesting meaningful symptom relief/remission of long Covid following use of PEMGARDA (pemivibart), a monoclonal antibody currently authorized by the US FDA for the pre-exposure prophylaxis (prevention) of Covid-19 in certain immunocompromised individuals. PEMGARDA is not authorized for the treatment of Long Covid. While these emerging reports are anecdotal and uncontrolled, they collectively support a longstanding, mechanistically plausible hypothesis: that prolonged exposure to pathogenic SARS-CoV-2 spike protein or other forms of persistent virus or viral material may drive disease in some patients, and that reducing this burden through monoclonal antibody therapy may offer a promising therapeutic approach worthy of rigorous clinical investigation. Clinical research to be planned by the SPEAR Study Group is critical to exploring disease biology and evaluating efficacy endpoints that can enable registrational studies if appropriate in the future.
The SPEAR Study Group includes the following investigators and researchers who, along with Invivyd, will collaborate on the design and anticipated execution of relevant clinical trials: Michael Peluso, Assistant Professor of Medicine, Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco. Amy Proal, co-founder and CEO, Polybio Research Foundation and Scientific Director, Mount Sinai Cohen Center for Recovery from Complex Chronic Diseases (CoRE). David Putrino, Nash family director of the Mount Sinai Cohen Center for Recovery from Complex Chronic Diseases (CoRE) and Professor, Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai.
The SPEAR Study Group intends to launch collaborative, multi-center translational clinical research on long Covid, including PVS, as soon as practicable, including use of next-generation monoclonal antibody candidates from Invivyd such as VYD2311.
“It is now clear from a growing body of high-quality, peer-reviewed research that persistent spike protein or viral reservoirs can be identified in a meaningful portion of people with recent long Covid,” said Dr. Peluso. “For the first time in years, there is a company with the capability to explore this space using active, broadly neutralizing monoclonal antibodies. This research marks an essential step toward understanding what may cause debilitating Covid-driven chronic disease, and we hope will lay the groundwork for future efficacy studies that could deliver real therapeutic options to patients who have waited far too long.”
“Long Covid is a pervasive, debilitating, and underappreciated public health challenge affecting millions of adults and children in the US, with no approved treatments,” said Marc Elia, Chairman of the Board at Invivyd. “Monoclonal antibodies have already demonstrated efficacy in preventing acute Covid-19 infections and treating acute Covid-19 infections, including long-term infections, and emerging anecdotal reports suggest pemivibart may have potential in addressing symptoms in some long Covid patients. We believe that monoclonal antibodies are key to managing the ongoing burden of endemic Covid-19 disease in all forms, and as previously disclosed, we will be meeting with the FDA early in 3Q to discuss rapid approval pathways for Covid-19 mAbs. Meanwhile, our formation of the SPEAR Study Group is a critical step toward potentially unlocking a long Covid treatment opportunity for patients in need by generating data needed to inform future studies and potential regulatory pathways. We look forward to sharing future milestones as we advance this important initiative.”
PEMGARDA (pemivibart) is a half-life extended investigational monoclonal antibody (mAb). PEMGARDA was engineered from adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and provided evidence of clinical efficacy in global phase 2/3 clinical trials for the prevention and treatment of Covid-19. PEMGARDA has demonstrated in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.1, KP.3.1.1, XEC and LP.8.1. PEMGARDA targets the SARS-CoV-2 spike protein receptor binding domain (RBD), thereby inhibiting virus attachment to the human ACE2 receptor on host cells.
Pemivibart injection (4500 mg), for intravenous use is an investigational mAb that has not been approved, but has been authorized for emergency use by the US FDA under an EUA for the pre-exposure prophylaxis (prevention) of Covid-19 in adults and adolescents (12 years of age and older weighing at least 40 kg) who have moderate-to-severe immune compromise due to certain medical conditions or receipt of certain immunosuppressive medications or treatments and are unlikely to mount an adequate immune response to Covid-19 vaccination. Recipients should not be currently infected with or have had a known recent exposure to an individual infected with SARS-CoV-2.
PEMGARDA is not authorized for use for treatment of Covid-19, treatment of long Covid, or post-exposure prophylaxis of Covid-19. Pre-exposure prophylaxis with PEMGARDA is not a substitute for vaccination in individuals for whom Covid-19 vaccination is recommended. Individuals for whom Covid-19 vaccination is recommended, including individuals with moderate-to-severe immune compromise who may derive benefit from Covid-19 vaccinations, should receive Covid-19 vaccination. In individuals who have recently received a Covid-19 vaccine, PEMGARDA should be administered at least 2 weeks after vaccination.
Anaphylaxis has been observed with PEMGARDA and the PEMGARDA Fact Sheet for Healthcare Providers includes a boxed warning for anaphylaxis. The most common adverse reactions included systemic infusion-related reactions and hypersensitivity reactions, local infusion site reactions, and infusion site infiltration or extravasation.
To support the EUA for PEMGARDA, an immunobridging approach was used to determine if PEMGARDA may be effective for pre-exposure prophylaxis of Covid-19. Immunobridging is based on the serum virus neutralizing titer-efficacy relationships identified with other neutralizing human mAbs against SARS-CoV-2. This includes adintrevimab, the parent mAb of pemivibart, and other mAbs that were previously authorized for EUA. There are limitations of the data supporting the benefits of PEMGARDA. Evidence of clinical efficacy for other neutralizing human mAbs against SARS-CoV-2 was based on different populations and SARS-CoV-2 variants that are no longer circulating. Further, the variability associated with cell-based EC50 value determinations, along with limitations related to pharmacokinetic data and efficacy estimates for the mAbs in prior clinical trials, impact the ability to precisely estimate protective titer ranges. Additionally, certain SARS-CoV-2 viral variants may emerge that have substantially reduced susceptibility to PEMGARDA, and PEMGARDA may not be effective at preventing Covid-19 caused by these SARS-CoV-2 viral variants.
The emergency use of PEMGARDA is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the Covid-19 pandemic under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner. PEMGARDA is authorized for use only when the combined national frequency of variants with substantially reduced susceptibility to PEMGARDA is less than or equal to 90%, based on available information including variant susceptibility to PEMGARDA and national variant frequencies.
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