Invivyd Announces U.S. FDA Has Updated the PEMGARDA™ EUA Fact Sheet with Accurate SARS-CoV-2 Variant Susceptibility and PEMGARDA Activity Data

Rhea-AI Summary

Invivyd (Nasdaq: IVVD) announced that the FDA has updated the Emergency Use Authorization (EUA) Fact Sheet for PEMGARDA™ (pemivibart) with accurate SARS-CoV-2 variant susceptibility data. The updated Fact Sheet, dated September 26, 2024, includes in vitro neutralization activity against dominant circulating variants, including KP.3.1.1 and LB.1, which is in line with prior variants represented in the CANOPY Phase 3 clinical trial.

The FDA removed a contested statement about reduced susceptibility to pemivibart for KP.3.1.1, based on data provided by LabCorp's Monogram Biosciences lab. Invivyd emphasizes the importance of relying on validated, scientific studies conducted with authentic pemivibart under industrial-quality conditions for assessing neutralization potency and variant susceptibility.

Positive

• FDA updated PEMGARDA's Fact Sheet with accurate variant susceptibility data
• PEMGARDA likely retains adequate neutralization activity against current SARS-CoV-2 variants
• In vitro neutralization potency values for KP.3.1.1 and LB.1 are in-line with prior variants

Negative

• Previous Fact Sheet contained contested statement about reduced susceptibility to pemivibart
• Potential for conflicting data from laboratories with competing interests

Insights

Medical Research Analyst

The FDA's update to the PEMGARDA™ (pemivibart) EUA Fact Sheet is a significant development for Invivyd. The removal of the statement about reduced susceptibility to the KP.3.1.1 variant and inclusion of data showing neutralization activity in line with previous variants is crucial for the product's credibility. This correction addresses concerns about PEMGARDA's effectiveness against current SARS-CoV-2 variants.

The emphasis on using validated, industrial-quality testing methods with authentic pemivibart highlights the importance of rigorous scientific processes in assessing COVID-19 antibody treatments. This approach ensures more reliable data for healthcare professionals and patients, potentially increasing confidence in PEMGARDA.

However, the incident underscores the challenges in rapidly evolving viral landscapes and the need for careful validation of preliminary data before inclusion in official documents. The company's commitment to ongoing variant monitoring and transparency with the FDA is positive for maintaining the product's relevance in the COVID-19 treatment landscape.

Financial Analyst

This update has significant implications for Invivyd's market position and potential revenue streams. The correction of potentially misleading information in the FDA Fact Sheet removes a major obstacle to PEMGARDA's market acceptance and could positively impact sales projections.

For a company with a market cap of $124,817,554, maintaining the viability of a key product like PEMGARDA is crucial. The clarification that the antibody treatment remains effective against current variants, including KP.3.1.1 and LB.1, preserves its competitive edge in the COVID-19 therapeutics market.

Investors should note the company's proactive approach in addressing data discrepancies and its collaboration with regulatory bodies. This demonstrates strong governance and risk management, which are positive indicators for long-term stability. However, the incident also highlights the volatility and scrutiny faced by companies in the COVID-19 treatment space, emphasizing the need for robust data management and communication strategies.

• KP.3.1.1 and LB.1 in vitro neutralization potency values now reflected in the PEMGARDA Fact Sheet for Healthcare Providers are in-line with prior variants, including variants represented in the CANOPY Phase 3 clinical trial
• Invivyd continues active variant monitoring using validated, robust methods and is not aware of any circulating variants not susceptible to PEMGARDA at this time

WALTHAM, Mass., Oct. 01, 2024 (GLOBE NEWSWIRE) -- Invivyd, Inc. (Nasdaq: IVVD), a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, announced today that the U.S. Food and Drug Administration (FDA) has re-issued an updated Emergency Use Authorization (EUA) Fact Sheet for Healthcare Providers (Fact Sheet) for PEMGARDA™ (pemivibart) to provide accurate in vitro neutralization activity of PEMGARDA against dominant circulating variants including KP.3.1.1 and LB.1.

The FDA’s newly updated Fact Sheet, dated September 26, 2024, removes a contested statement that “preliminary, non-peer-reviewed data in the public domain indicate that KP.3.1.1 may have substantially reduced susceptibility to pemivibart.” The FDA has now included viral neutralization data for pemivibart that is in line with prior variants represented in the CANOPY Phase 3 clinical trial based on data generated by LabCorp's Monogram Biosciences lab and provided to the FDA on September 3, 2024, and determined that PEMGARDA is likely to retain adequate neutralization activity against SARS-CoV-2 variants currently circulating in the U.S., including KP.3.1.1 (FDA updates PEMGARDA’s SARS-CoV-2 variant susceptibility data).

Various laboratories, which may have competing or conflicting interests with Invivyd’s core COVID-19 antibody business, may produce their own reagents meant to resemble pemivibart, and may put neutralization findings of unknown quality into the public domain. Invivyd, as a matter of policy and in partnership with the FDA, relies on the high standard of assessing authentic pemivibart under industrial-quality conditions to assess pemivibart neutralization potency and likely variant susceptibility. Such procedural rigor is critical given the difficulty of cellular bioassay development and validation and intrinsic quantitative variability of these assays even when conducted under highly controlled conditions. Invivyd encourages all stakeholders to rely on validated, scientific studies conducted with authentic pemivibart and to exercise caution when assessing the potential relevance of virology work performed under conditions of questionable quality and control.

“The updated PEMGARDA Fact Sheet corrects a confusing and avoidable chapter of the product’s lifecycle,” commented Marc Elia, Chairman of the Invivyd Board of Directors. “Accurate and reliable industrial-grade applications of virology, using the actual pharmaceutical agent authorized for medical use, are central for healthcare professionals, patients and other stakeholders to understand the risk-benefit profile of PEMGARDA in this current regulatory paradigm, which relies heavily on in vitro neutralization assays and activity. We at Invivyd applaud scientific research, though in this instance, early science with known questionable attributes infiltrated a product Fact Sheet that stakeholders rely upon for important decision making; such an approach can be damaging. Sponsors and regulators alike serve a common medical goal, and it is clear we should do better going forward.”

As previously communicated, Invivyd relies on extensive structural analysis to understand the stability of the pemivibart binding site and uses neutralization bioassays to assess the possible influence of epistasis and allostery. The company will continue to assess variant susceptibility in partnership with the FDA, subject to the clear requirements in the PEMGARDA Letter of Authorization.

About PEMGARDA  
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 a global Phase 2/3 clinical trial for the prevention and treatment of COVID-19. PEMGARDA has demonstrated in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.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 injection (4500 mg), for intravenous use is an investigational mAb that has not been approved, but has been authorized for emergency use by the U.S. 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 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 events (all grades, incidence ≥2%) observed in participants who have moderate-to-severe immune compromise treated with PEMGARDA included systemic and local infusion-related or hypersensitivity reactions, upper respiratory tract infection, viral infection, influenza-like illness, fatigue, headache, and nausea. 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.  

About Invivyd  
Invivyd, Inc. (Nasdaq: IVVD) is a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2. The company’s proprietary INVYMAB™ platform approach combines state-of-the-art viral surveillance and predictive modeling with advanced antibody engineering. INVYMAB is designed to facilitate the rapid, serial generation of new monoclonal antibodies (mAbs) to address evolving viral threats. In March 2024, Invivyd received emergency use authorization (EUA) from the U.S. FDA for its first mAb in a planned series of innovative antibody candidates. Visit https://invivyd.com/ to learn more.  

Cautionary Note Regarding Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “could,” “expects,” “estimates,” “intends,” “potential,” “projects,” and “future” or similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements include statements concerning, among other things, the company’s ongoing research and clinical development activities, as well as future potential research and clinical development efforts; the company’s active SARS-CoV-2 variant monitoring and ongoing efforts to assess authentic pemivibart under industrial-quality conditions to assess pemivibart neutralization potency and likely variant susceptibility; expectations regarding PEMGARDA’s likelihood of retaining adequate neutralization activity; the possibility that various laboratories may put neutralization findings of unknown quality into the public domain; Invivyd’s beliefs regarding the importance of accurate and reliable industrial-grade applications of virology, using the actual pharmaceutical agent authorized for medical use, and the caution to be exercised when assessing the potential relevance of virology work performed under conditions of questionable quality and control; Invivyd’s plans to continue to assess variant susceptibility in partnership with the FDA, subject to the clear requirements in the PEMGARDA Letter of Authorization; the potential of PEMGARDA as a mAb for pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and adolescents who have moderate-to-severe immune compromise; the company’s devotion to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2; the design of the company’s INVYMAB platform approach to facilitate the rapid, serial generation of new mAbs to address evolving viral threats; and other statements that are not historical fact. The company may not actually achieve the plans, intentions or expectations disclosed in the company’s forward-looking statements and you should not place undue reliance on the company’s forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause the company’s actual results to differ materially from the results described in or implied by the forward-looking statements, including, without limitation: the timing, progress and results of the company’s discovery, preclinical and clinical development activities; the risk that results of nonclinical studies or clinical trials may not be predictive of future results, and interim data are subject to further analysis; unexpected safety or efficacy data observed during preclinical studies or clinical trials; the predictability of clinical success of the company’s product candidates based on neutralizing activity in nonclinical studies; potential variability in neutralizing activity of product candidates tested in different assays, such as pseudovirus assays and authentic assays; the company’s reliance on third parties with respect to virus assay creation and product candidate testing and with respect to its clinical trials; variability of results in models used to predict activity against SARS-CoV-2 variants; whether pemivibart or any other product candidate is able to demonstrate and sustain neutralizing activity against major SARS-CoV-2 variants, particularly in the face of viral evolution; how long the EUA granted by the FDA for PEMGARDA will remain in effect and whether the EUA is revoked or revised by the FDA; the company’s ability to build and maintain sales, marketing and distribution capabilities to successfully commercialize PEMGARDA; uncertainties related to the regulatory authorization or approval process, and available development and regulatory pathways for authorization or approval of the company’s product candidates; the ability to maintain a continued acceptable safety, tolerability and efficacy profile of any product candidate following regulatory authorization or approval; changes in the regulatory environment; changes in expected or existing competition; the complexities of manufacturing mAb therapies; the company’s ability to leverage its INVYMAB platform approach to facilitate the rapid, serial generation of new mAbs to address evolving viral threats; any legal proceedings or investigations relating to the company; the company’s ability to continue as a going concern; and whether the company has adequate funding to meet future operating expenses and capital expenditure requirements. Other factors that may cause the company’s actual results to differ materially from those expressed or implied in the forward-looking statements in this press release are described under the heading “Risk Factors” in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, each filed with the Securities and Exchange Commission (SEC), and in the company’s other filings with the SEC, and in its future reports to be filed with the SEC and available at www.sec.gov. Forward-looking statements contained in this press release are made as of this date, and Invivyd undertakes no duty to update such information whether as a result of new information, future events or otherwise, except as required under applicable law.  

This press release contains hyperlinks to information that is not deemed to be incorporated by reference in this press release.   

Contacts:  
Media Relations  
(781) 208-0160  
media@invivyd.com 

Investor Relations  
(781) 208-0160  
investors@invivyd.com

FAQ

What updates did the FDA make to PEMGARDA's EUA Fact Sheet for IVVD?

The FDA updated PEMGARDA's EUA Fact Sheet with accurate in vitro neutralization activity data against dominant circulating SARS-CoV-2 variants, including KP.3.1.1 and LB.1. They removed a contested statement about reduced susceptibility and confirmed that PEMGARDA likely retains adequate neutralization activity against current variants.

How does PEMGARDA's effectiveness against new SARS-CoV-2 variants compare to previous ones for IVVD?

According to the updated FDA Fact Sheet, PEMGARDA's in vitro neutralization potency values for new variants KP.3.1.1 and LB.1 are in-line with prior variants, including those represented in the CANOPY Phase 3 clinical trial. This suggests consistent effectiveness across different SARS-CoV-2 variants.

What is Invivyd's approach to monitoring SARS-CoV-2 variants for PEMGARDA (IVVD)?

Invivyd uses extensive structural analysis to understand the stability of the pemivibart binding site and employs neutralization bioassays to assess the influence of epistasis and allostery. The company conducts active variant monitoring using validated, robust methods in partnership with the FDA, adhering to requirements in the PEMGARDA Letter of Authorization.

Why does Invivyd (IVVD) emphasize the use of authentic pemivibart in neutralization studies?

Invivyd emphasizes using authentic pemivibart under industrial-quality conditions because cellular bioassay development and validation are difficult, and these assays have intrinsic quantitative variability. Using the actual pharmaceutical agent authorized for medical use ensures accurate and reliable results for assessing PEMGARDA's effectiveness against SARS-CoV-2 variants.