8-K: Invivyd Submits Positive Data Analysis to FDA for PEMGARDA COVID-19 Treatment EUA Amendment

Invivyd has provided the FDA with updated data showing pemivibart has substantially higher antiviral activity than adintrevimab, supporting its request to expand the Emergency Use Authorization (EUA) for PEMGARDA to include treatment of mild-to-moderate COVID-19 in certain immunocompromised patients.

Summary

• Invivyd has submitted an updated immunobridging analysis to the FDA for pemivibart, a monoclonal antibody, to support an amendment to its Emergency Use Authorization (EUA).
• The analysis compares pemivibart's antiviral activity to adintrevimab, a previous COVID-19 treatment, showing pemivibart has substantially higher antiviral titers in the critical early phase post-dosing (Days 0-5).
• The data includes neutralization data for the current dominant SARS-CoV-2 variant XEC.
• The company is seeking to expand PEMGARDA's EUA to include treatment of mild-to-moderate COVID-19 in certain immunocompromised patients.
• PEMGARDA already has an EUA for pre-exposure prophylaxis (PrEP) of COVID-19 in certain immunocompromised individuals, granted in March 2024.
• The updated analysis builds upon previous submissions to the FDA starting in July 2024, all showing consistent antiviral titer relationships.
• The company believes pemivibart's pharmacodynamic profile, due to intravenous dosing, may offer benefits in modifying viral infection compared to intramuscular adintrevimab.
• The company intends to assess the virologic profile of pemivibart in a clinical study if the EUA amendment is granted.
• The EUA process does not have a statutory timeline like PDUFA-based regulatory actions.

Sentiment

Score: 7

Explanation: The document presents positive data supporting the potential expansion of PEMGARDA's use, but also acknowledges risks and uncertainties associated with regulatory approval and future viral variants. The sentiment is cautiously optimistic.

Positives

• Pemivibart demonstrates substantially higher antiviral titers compared to adintrevimab in the critical early phase post-dosing.
• The updated analysis includes data on the current dominant SARS-CoV-2 variant XEC.
• Pemivibart's intravenous administration allows for higher serum drug concentration and immediate antiviral activity.
• No new cases of anaphylaxis have been reported during post-authorization use of PEMGARDA for pre-exposure prophylaxis.
• The company believes pemivibart could be a long-term option for vulnerable, immunocompromised persons.
• The company has provided consistent, timely updates to the FDA as SARS-CoV-2 virus variation has presented.

Negatives

• The EUA process does not have a statutory timeline, creating uncertainty around approval timing.
• There are limitations of the data supporting the benefits of PEMGARDA, including the variability associated with cell-based EC50 value determinations.
• Certain SARS-CoV-2 viral variants may emerge that have substantially reduced susceptibility to PEMGARDA.
• 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.

Risks

• The outcome of the EUA amendment request for pemivibart is uncertain.
• The EUA for PEMGARDA could be revised or revoked by the FDA.
• There are risks associated with the regulatory authorization or approval process.
• The company may not be able to maintain an acceptable safety, tolerability, and efficacy profile of pemivibart.
• The company relies on third parties for virus assay creation and product candidate testing.
• There is a risk that pemivibart may not be effective against future SARS-CoV-2 variants.
• The company's ability to maintain and expand sales, marketing and distribution capabilities to successfully commercialize PEMGARDA is a risk.
• The company's ability to continue as a going concern is a risk.

Future Outlook

Invivyd intends to assess the virologic profile of pemivibart in a clinical study designed in collaboration with the FDA if the EUA amendment for COVID-19 treatment is granted. The company believes pemivibart could be a long-term option for vulnerable, immunocompromised persons.

Management Comments

• Amesh Adalja, MD, stated that monoclonal antibodies have been highly attractive therapeutic options in the past and the community would welcome the return of a therapeutic mAb.
• Invivyd believes that the performance of Invivyd antibodies based on sVNA titers represents a well-supported surrogate endpoint and should be considered for approval beyond EUA.

Industry Context

This announcement is significant as it addresses the ongoing need for effective COVID-19 treatments, particularly for immunocompromised individuals who may not respond well to other therapies. The potential approval of pemivibart for treatment would reintroduce monoclonal antibody therapy as a viable option, which has been limited due to the emergence of new variants.

Comparison to Industry Standards

• The document references adintrevimab, a previous monoclonal antibody from Invivyd, which demonstrated a 66% to 74% reduction in risk of hospitalization or death from COVID-19 compared to placebo.
• The document compares pemivibart to other monoclonal antibodies previously authorized for treatment of COVID-19, suggesting a benchmark for efficacy.
• The document mentions PAXLOVID (nirmatrelvir) as a current standard of care, highlighting the limitations of drug-drug interactions and the need for alternative treatments.
• The document references a study by Hammond et al in NEJM 2022, which provides context for the effectiveness of antiviral treatments.
• The document references a study by Ison et al in Open Forum Infect Dis. 2023, which underscores the benefit of deploying maximum antiviral activity as early as possible in the treatment of active infection.

Stakeholder Impact

• Shareholders may react positively to the potential expansion of PEMGARDA's market.
• Immunocompromised patients could benefit from an additional treatment option.
• Healthcare providers would have another tool to combat COVID-19.
• The company's employees may be impacted by the workload associated with the regulatory process and potential commercialization.

Next Steps

• The FDA will review the updated immunobridging analysis for pemivibart.
• Invivyd intends to assess the virologic profile of pemivibart in a clinical study if the EUA amendment is granted.

Key Dates

Keywords

PEMGARDA, pemivibart, COVID-19, EUA, monoclonal antibody, immunocompromised, FDA, adintrevimab, antiviral, SARS-CoV-2, treatment, pre-exposure prophylaxis, PrEP