With the FDA granting emergency use authorization (EUA) to Invivyd’s lead candidate, a monoclonal antibody (mAb) designed to prevent COVID-19 in immunocompromised adults and adolescents, the company has succeeded in its two-year quest to rise from the ashes of its predecessor Adagio Therapeutics.

The FDA authorized Pemgarda™ (pemivibart), a mAb re-engineered from Adagio’s failed lead candidate ADG20—which Invivyd is still working to develop under the name adintrevimab.

Pemgarda is indicated for prevention of COVID-19 in adults and adolescents ages 12 and older, weighing at least 40 kg (88 pounds) with moderate-to-severe immune compromise due to certain medical conditions or effects of certain immunosuppressive medications or treatments, and are unlikely to mount an adequate immune response to COVID-19 vaccination.

Invivyd plans to detail how it will make Pemgarda available to patients “within a week or so,” CEO Dave Hering told GEN Edge.

Hering said Invivyd will initially focus its commercial efforts on a 485,000-person slice of the nation’s nine million immunocompromised people who are moderately to severely immunocompromised, and thus at highest risk for COVID-19. Of that 485,000, more than two-thirds (332,000 or 68%) have various blood cancers, while 86,000 (18%) are solid organ transplant recipients (liver, lung, and kidney), and the remaining 67,000 (14%) are stem cell transplant recipients.

Defined population

That defined population, Invivyd reasons, will help Pemgarda to succeed in a field of COVID-19 drugs and vaccines whose sales have shriveled as the pandemic evolved into an endemic.

Pfizer’s top-selling COVID-19 drug, the antiviral pill Paxlovid (nirmatrelvir and ritonavir) saw its sales crater 93% last year, to $1.279 billion from $18.933 billion in 2022, while its top-selling COVID-19 vaccine Comirnaty® (COVID-19 Vaccine, mRNA), co-developed with BioNTech, plunged 70%, to $11.22 billion from $37.806 billion. Moderna’s Spikevax® vaccine sales skidded 64%, to $6.671 billion from $18.435 billion.

“We see still that the need for ongoing COVID-19 products is basically going to meet a leveling off point. But for monoclonal antibodies, we think that there’s a tremendous ramp up, whereas for a lot of the other products, vaccines or antivirals, that were heavily utilized, they’re coming down,” Hering said. “We’ll reach a new status quo because monoclonal antibodies haven’t been on the market at the same level that the vaccines and antivirals have been. That is why we think that there is still a tremendous amount of need and increase for mAbs.”

Invivyd has hired a sales and marketing leadership team consisting of a vp of sales and regional sales managers, with 20–25 contracted key account managers (KAMs) now being engaged and trained. The KAMs will target the estimated 1,150 U.S. institutions that provide care to about 70% of the 485,000 moderately to severely immunocompromised patients that are the company’s initial focus.

“A good chunk of those KAMs already have accepted offers, though not all of them,” Hering said. “We’re in the process of onboarding them and training them to be able to have them be ready to be out in the field and interacting with HCPs [healthcare providers] in the very near term.”

Pemgarda’s list price had yet to be set at deadline, and Invivyd has not issued a sales forecast for the antibody.

Pemgarda differs from adintrevimab by eight amino acids within the variable region—a difference that allows it to shift slightly where it binds with the spike protein of SARS-CoV-2. That change makes Pemgarda much better able than adintrevimab to prevent symptomatic COVID-19 as the virus rapidly evolves, forming new variants, according to Invivyd.

“Always ensure binding”

“By shifting these amino acids, what we’re doing is slightly modifying where the antibody binds to the virus,” Hering explained. “We want to always ensure binding, because once you have binding, that is what really leads to the neutralization of the virus in the blood.”

The re-engineering also allowed Invivyd to apply a new regulatory framework for its Phase III trial allowing “immunobridging” through the use of data from serum-neutralizing titers as, well as previously generated clinical trial data from a prototype mAb—in this case, adintrevimab.

The evidence underpinning Pemgarda’s EUA included data showing that immunobridging was established in the Phase III CANOPY pivotal trial (NCT06039449), designed to assess the drug’s ability to protect against symptomatic COVID-19 at a 4,500 mg dose. Invivyd showed that the calculated serum neutralizing antibody titers against JN.1—now the dominant COVID-19 variant in the United States according to the Centers for Disease Control and Prevention (CDC)—were consistent with the titer levels associated with efficacy in prior clinical trials of monoclonal antibodies, including adintrevimab.

As it announced the EUA, Invivyd also released additional exploratory data from CANOPY that showed clinical protection from symptomatic COVID-19 stretching 90 days in all but one of the 314 patients dosed with Pemgarda—an open-label cohort with moderate-to-severe immune-compromised patients.

By contrast, eight patients randomized to placebo showed RT-PCR-confirmed symptomatic COVID-19 in a cohort of 159 adults without moderate-to-severe immune compromise who were at risk of acquiring SARS-CoV-2 due to regular unmasked face-to-face interactions in indoor settings.

The data was not part of Invivyd’s EUA filing or its review by the FDA, though the company said it may use the data to generate hypotheses for future discovery and development of Pemgarda.

“We’ll use the data as we think through future trials,” Hering said. “We keep having conversations with the FDA to better understand what the path would be for a BLA [Biologics License Application]”.

Annual updates

Among Invivyd’s goals, he added, is obtaining FDA approval for a license that would enable the company to update its vaccines annually in response to new or resurging variants, as with influenza vaccines: “We continue to feel that the virus will evolve and mutate, and at some point will require an updated mAb. So, we want to have a pathway to be able to do that going forward.”

Pemgarda was developed using INVYMAB™, Invivyd’s platform approach which combines viral surveillance and predictive modeling with advanced antibody engineering. INVYMAB is designed to enable rapid, serial generation of durable mAbs targeting conserved epitopes that could be deployed to keep pace with SARS-CoV-2 viral evolution or other viruses.

Investors initially roared their approval of the FDA EUA decision with a buying surge that sent Invivyd shares soaring 41% on Friday, from $3.09 to $4.36, before the stock succumbed to profit-taking, dropping 26% to $3.23 on Monday. While the surge did not reach the stock’s all-time high closing price of $5.04 on February 8, Invivyd remains close to the level it has traded at since it more than doubled, zooming 120% from $1.63 to $3.59 on December 18.

That day, Invivyd announced initial positive data from CANOPY in which Pemgarda—then named VYD222—produced high serum virus neutralizing antibody (sVNA) titer levels against the Omicron XBB.1.5 variant of COVID-19 in a cohort of approximately 300 patients who were significantly immunocompromised. The results essentially replicated the titer levels observed in the company’s Phase I trial (NCT05791318), showing that a single administration of VYD222 was generally well-tolerated in healthy adult volunteers at all three dose levels tested with no serious adverse events. All dose levels tested showed robust neutralization activity against Omicron XBB.1.5 at Day 7.

Invivyd submitted its EUA request to the FDA in early January.

Adintrevimab and Pemgarda are the only two named candidates listed in Invivyd’s pipeline. The company has three other COVID-19 mAb candidates, identified only as #2, #3, and #4, in discovery and preclinical phases—plus a mAb combination candidate for prevention of influenza, in the early discovery phase.

Adintrevimab remains under development for both COVID-19 prevention and COVID-19 treatment. Adintrevimab trials for both conditions have concluded, and Invivyd says it has a package of data ready to submit for an EUA filing dependent on variant susceptibility.

“One of the things we keep doing from the research side is testing it against new variants. So, that continues, and we’re always looking to see what its activity would be against some of those variants,” Hering said. “It is something that we continue to actively monitor and look at.”

Previous articleCulprit behind Psoriasis Revealed
Next articleAllergic Asthma Could Be Calmed by Flipping Immune Cell Switch