Invivyd's PEMGARDA (pemivibart) receives from FDA the Emergency Use Authorization (EUA) for the pre-exposure prophylaxis (PrEP) of COVID-19 in adults and adolescents with moderate-to-severe immune compromise

On March 22^nd, 2024 the FDA announced that it had granted Emergency Use Authorization to Invivyd’s PEMGARDA (IV, anti-SARS-CoV-2 nAb, 4500mg, generic name pemivibart, development name VYD222) for the pre-exposure prophylaxis (PrEP) of COVID-19 in certain adults and adolescents with moderate-to-severe immune compromise.

Key Highlights

Indication

• PEMGARDA is indicated for the PrEP of COVID-19 in adults and adolescents (≥12 years old; ≥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. PEMGARDA’s initial Dose is 4500 mg administered as a single IV infusion with 4500 mg repeat IV infusions ~every 3 months afterward
  • PEMGARDA is not authorized for the treatment of COVID-19 or for post-exposure prophylaxis in individuals who have been exposed to someone infected with SARS-CoV-2
• The FDA EUA is based upon positive immunobridging data and on safety data from the Ph3 CANOPY clinical trial along with ongoing in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.1 
• PEMGARDA is the first PrEP nAb to receive FDA EUA based on the immunobridging trial design concept. The company also expressed plans to explore the protective clinical benefits of nAb prophylaxis for symptomatic COVID-19 disease in future studies

Commercial Plans 

• Invivyd noted that out of the >9M IC patients in the US, the initial commercial focus will be targeted towards the highest-risk moderate-to-severe IC groups (Total: ~485K; Stem Cell Transplant pts: 67K; Solid Organ Transplant pts (liver/lung/kidney): 86K; Hematologic cancer pts: 332K). The company stated that PEMGARDA is expected to be available imminently with the initial supply already packaged and awaiting final release through 3^rd-party distributors. Invivyd has also outlined its commercial organization structure and sales and marketing plan to support PEMGARDA launch (see screenshot below)
• Invivyd did not mention any plans for the commercialization of PEMGARDA outside of the US, and management noted future efficacy studies will be needed for a standard BLA approval

• Omicron variants have largely rendered 1^st-generation nAb products ineffective until PEMGARDA. While the risk remains that next-gen nAbs like PEMGARDA may lose activity against future variants, the immunobridging process may mitigate this challenge by providing nAb manufacturers an expedited means to continually launch viable nAb therapies.
  • AstraZeneca’s sipavibart is also being developed using this immunobridging approach as a prophylactic therapy for IC patients but its Ph3 SUPERNOVA trial has had several delays due to the Omicron XBB1.5 F456L mutation. This variant was the dominant strain across the EU/US throughout 2023 and previous data at IDWeek 2023 demonstrated sipavibart’s significant limited neutralization activity.
  • It remains to be seen how nAbs may be authorized/revoked on a routine basis in response to the currently circulating variants. With immunobridging now an accepted development protocol for COVID-19 therapeutics, there may be increased efforts from nAb competitors to develop new products routinely for treatment and prevention indications.

Sources: EUA Label, FDA LoA and Invivyd press release / presentation. A webcast to the company’s EUA conference call can be found here