- Unique, rapid development pathway for monoclonal antibodies (mAbs) using immunobridging via serum neutralizing titers could be enabled by previously generated clinical trial data from prototype antibody
- VYD222 and potential future Invivyd mAbs are planned to leverage this EUA pathway using consistent manufacturing platform and limited structural changes from proprietary prototype antibody ADG20 (adintrevimab)
- Company confirms plans to pursue rapid initiation of a VYD222 pivotal clinical trial using serum neutralizing titers as a correlate of protection (surrogate endpoint) to rapidly generate data for a potential VYD222 EUA submission
WALTHAM, Mass., June 26, 2023 (GLOBE NEWSWIRE) -- Invivyd, Inc. (Nasdaq: IVVD), a clinical-stage biopharmaceutical company on a mission to protect the vulnerable from serious viral infectious diseases, today announced that it has reached general alignment with the U.S. Food and Drug Administration (FDA) on a pathway to potential emergency use authorization (EUA) for VYD222 and anticipated follow-on monoclonal antibody (mAb) candidates designed to prevent symptomatic COVID-19. The company plans to leverage the pathway, which includes the use of serum neutralizing titers as a correlate of protection (surrogate of clinical efficacy) in an immunobridging approach to a pivotal clinical trial of VYD222, to rapidly generate data to support a potential VYD222 EUA for the prevention of symptomatic COVID-19. Based on FDA feedback, the use of a correlate of protection in an immunobridging approach to a pivotal EUA-directed clinical trial may be a reasonable approach for a new mAb candidate when clinical trial data from a “prototype” mAb is available, provided that the new mAb candidate: (1) is similar to the prototype mAb such that it leverages a consistent manufacturing platform and has limited structural and functional differences, and (2) has supportive nonclinical data, such as favorable in vitro neutralization data against currently circulating SARS-CoV-2 variants.
Invivyd plans to leverage this immunobridging pathway to accelerate the clinical development of VYD222 and anticipated follow-on mAb candidates, with ADG20 (adintrevimab) or future proprietary mAbs serving as the prototype. The use of adintrevimab as the potential prototype mAb is proprietary to Invivyd and enabled by the robust safety data and clinically meaningful results from a global Phase 2/3 clinical trial of adintrevimab for the prevention of symptomatic COVID-19. VYD222 is a broadly neutralizing, half-life extended mAb candidate in development for the prevention of symptomatic COVID-19 in vulnerable populations, such as immunocompromised people. VYD222 was designed for broad activity and has previously demonstrated in vitro neutralizing activity against prior circulating SARS-CoV-2 variants and current variants of concern, including Omicron sublineages up to and through XBB.1.5.
In June 2023, the company announced positive initial safety and serum neutralizing titer data from the ongoing Phase 1 VYD222 clinical trial. Serum neutralizing titers are the same surrogate marker planned for use in the primary endpoint in a pivotal VYD222 clinical trial.
“We are very encouraged by the recent feedback from the FDA and appreciate their commitment to exploring alternative strategies to expedite the development of mAbs for the prevention of symptomatic COVID-19, such as the use of a correlate of protection as the primary endpoint in a pivotal clinical trial, a strategy that we are pleased to see further advance following the joint EMA-FDA workshop last December where the approach was discussed,” said Dave Hering, chief executive officer of Invivyd. “Given our previous work developing adintrevimab and our platform-based approach to rapid mAb discovery, we believe we are one of few companies positioned to rapidly and serially generate data for potential EUA submission for next-generation mAb candidates for the prevention of symptomatic COVID-19. This potential pathway supports the company’s vision and strategy of establishing a platform and stream of optimized anti-SARS-CoV-2 mAb candidates that can be deployed to keep pace with viral evolution and protect the vulnerable.”
Invivyd continues activities to prepare for a VYD222 pivotal clinical trial and is pursuing a rapid initiation of that clinical trial in order to support a potential EUA submission. The company also continues to engage with global regulatory authorities regarding the VYD222 clinical development program.
About the Phase 1 Clinical Trial of VYD222
The ongoing VYD222 Phase 1 clinical trial is a randomized, blinded, placebo-controlled, dose-ranging trial that will evaluate the safety, pharmacokinetics, tolerability, and serum virus neutralizing activity of VYD222 in healthy adult volunteers (NCT05791318). The dose-ranging trial will evaluate three different doses of VYD222, each administered as a single IV push. All doses are designed to provide durability in the face of viral evolution and flexibility at the time of regulatory submission. In May 2023, Invivyd finished dosing all 30 participants in the trial; follow up is ongoing.
About VYD222
VYD222 is a broadly neutralizing, half-life extended monoclonal antibody (mAb) candidate in development for the prevention of symptomatic COVID-19 in vulnerable populations, such as immunocompromised people. Globally, there are millions of immunocompromised people, with an estimated 8-18 million in the U.S. alone, who may not adequately respond to COVID-19 vaccination, increasing their risk for severe outcomes from COVID-19. As of June 2023, there are no monoclonal antibodies authorized or approved in the U.S. for the prevention of symptomatic COVID-19.
VYD222 was designed for broad activity and has demonstrated in vitro neutralizing activity against previously circulating SARS-CoV-2 variants and current variants of concern, including Omicron sub-lineages up to and through XBB.1.5. VYD222 was engineered from 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 both the prevention and treatment of COVID-19. The company believes the adintrevimab clinical data have the potential to support accelerated development of VYD222.
About the Phase 2/3 Clinical Trial of Adintrevimab for the Prevention of COVID-19 (EVADE)
EVADE was a multi-center, double-blind, placebo-controlled, randomized Phase 2/3 clinical trial of adintrevimab for post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) of symptomatic COVID-19 in SARS-CoV-2 naïve, unvaccinated individuals (NCT04859517). Eighty-eight sites randomized 2,582 participants in 8 countries. Eligible participants were adults (≥18 years) and adolescents (12 to