Invivyd Announces Continued Neutralizing Activity of PEMGARDA & VYD2311 Against Currently Dominant SARS-CoV-2 Variant XFG

Invivyd, Inc. recently announced positive, continued, clinically meaningful in vitro neutralization data for PEMGARDA (pemivibart) against the currently dominant and growing XFG variant of SARS-CoV-2. Notably, and consistent with all dominant variants for the past three years, XFG did not generate any meaningful change to the in vitro neutralization activity of pemivibart or VYD2311, the company’s next-generation COVID-19 monoclonal antibody (mAb) candidate, as the epitopes targeted by pemivibart and VYD2311 remain structurally intact. PEMGARDA (pemivibart) is authorized by the US FDA for pre-exposure prophylaxis of COVID-19 in certain immuno-compromised patients.

Currently, the level of COVID-19 viral activity detected in wastewater in 12 states is reported as high or very high levels as of early August, and the US Centers for Disease Control and Prevention (CDC) estimates that COVID-19 infections are growing or likely growing in 34 states and declining in zero states, according to forecasting models. Further, the company estimates that every clinical variant reported in the CDC COVID Data Tracker since the Omicron BA.2 lineage has been susceptible to pemivibart, even if untested, due to the consistent structural integrity of the epitope targeted by pemivibart. Therefore, Invivyd anticipates continued meaningful clinical activity for pemivibart for the foreseeable future if the epitope pemivibart targets remains intact.

“COVID-19 activity is once again on the rise across much of the US, with wastewater data and forecasting models pointing to sustained growth in infections. Against this backdrop, we are pleased but not surprised that pemivibart has continued to demonstrate neutralizing activity against the currently dominant XFG variant, and we look forward to rapidly advancing our next-generation antibody VYD2311 which has shown similar in vitro neutralization results at much higher potency. The demonstrated stability of the epitopes our monoclonal antibodies target across SARS-CoV-2 evolution underscores the strength of our molecular design strategy and our capability in creating high-barrier-to-resistance medicines,” said Robert Allen, PhD, Chief Scientific Officer of Invivyd.

“For people whose immune systems may not get enough protection from vaccines such as those on immunosuppressive therapies and those undergoing cancer treatment, each new COVID-19 wave can create additional challenges and disrupt care,” added Tim Lee, Chief Commercial Officer of Invivyd. “Pemivibart has shown extraordinary continuing in vitro neutralization activity against SARS-CoV-2 over now several years, and our next-generation antibody VYD2311 represents another hopeful step toward more scalable protection with a more patient-friendly route of administration.”

Data showing continued in vitro neutralizing activity of PEMGARDA^® (pemivibart) against XFG and other circulating viruses will be provided to the FDA imminently, with anticipated inclusion in the PEMGARDA Fact Sheet for Healthcare Providers.

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.

PEMGARDA (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. For additional information, please see the PEMGARDA full product Fact Sheet for Healthcare Providers, including important safety information and boxed warning.

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.

VYD2311 is a novel monoclonal antibody (mAb) candidate being developed for COVID-19 to continue to address the urgent need for new prophylactic and therapeutic options. The pharmacokinetic profile and antiviral potency of VYD2311 may offer the ability to deliver clinically meaningful titer levels through more patient-friendly means such as an intramuscular route of administration.

VYD2311 was engineered using Invivyd’s proprietary integrated technology platform and is the product of serial molecular evolution designed to generate an antibody optimized for neutralizing contemporary virus lineages. VYD2311 leverages the same antibody backbone as pemivibart, Invivyd’s investigational mAb granted emergency use authorization in the U.S. for the pre-exposure prophylaxis (PrEP) of symptomatic COVID-19 in certain immunocompromised patients, and adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and demonstrated clinically meaningful results in global Phase 2/3 clinical trials for the prevention and treatment of COVID-19.

Invivyd, Inc. is a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2. Invivyd deploys a proprietary integrated technology platform unique in the industry designed to assess, monitor, develop, and adapt to create best-in-class antibodies. In March 2024, Invivyd received emergency use authorization (EUA) from the US FDA for a monoclonal antibody (mAb) in its pipeline of innovative antibody candidates. Visit https://invivyd.com/ to learn more.