RSV antibody drug for infants approved by FDA in win for Sanofi and AstraZeneca

The fight against one of the world’s most common respiratory viruses just got another weapon.

On Monday, the FDA approved Beyfortus, an antibody drug co-developed by Sanofi and AstraZeneca. Beyfortus, also known as nirsevimab, is given as a one-time intramuscular injection to infants, protecting them from respiratory syncytial virus, or RSV. The drug won European approval in November.

Beyfortus is the latest in a suite of new medicines against RSV, a virus that typically puts 58,000 to 80,000 young children in the US in the hospital every year. Earlier this year, the FDA approved two RSV vaccines for older adults: GSK’s Arexvy and Pfizer’s Abrysvo. Wall Street analysts expect all these new medicines to grow into blockbusters over the next decade.

“What an exciting year for RSV and for babies everywhere,” Jon Heinrichs, Sanofi’s global project head in R&D for nirsevimab, told Endpoints News in an advance interview.

Jon Heinrichs

Beyfortus is the first new RSV treatment for infants in over two decades, following the 1998 approval of Synagis, an antibody drug sold by the Swedish drugmaker Sobi. While Synagis showed a 55% decrease in hospitalizations, Beyfortus cut the hospitalization rate by 83% in a Phase IIIb study enrolling over 8,000 infants in Europe and the UK during the last RSV season.

Wall Street analysts view RSV as one of the largest new markets in the drug industry, with Jefferies analysts predicting it will be a $17 billion global market by 2033, surpassing both Covid-19 and flu. They forecast $3.25 billion in peak sales of Beyfortus if it has a US price of $400 to $500. Sanofi has yet to announce a pricing decision; however, a company spokesperson said the company expects it to be “priced similarly to an innovative pediatric vaccine series.”

Beyfortus has a fairly convoluted ownership history involving AstraZeneca, Sanofi and Sobi. In 2018, after AstraZeneca and Sanofi struck a deal to co-develop the drug, Sobi bought rights to a share of AstraZeneca’s US profits from Beyfortus in a larger divestment deal. While AstraZeneca and Sanofi split the ex-US market, Sanofi gained full control over the US market when it reworked these alliances in April. Through the newest arrangement, Sanofi will pay US net sales royalties to Sobi ranging from 25% to 35%.

NIH breakthrough in 2013 leads to new, improved antibody drug 

Like the new RSV vaccines, Beyfortus came out of a research breakthrough in 2013. Researchers at the National Institutes of Health figured out how a key protein of the virus works. RSV uses the fusion protein, or F protein, to slip inside and infect cells. But the F protein changes between two shapes, its pre- and post-fusion forms. While a postdoctoral researcher at the NIH, Jason McLellan was able to crack the structure of the prefusion F protein and also find a way to lock it in place.

Jason McLellan

AstraZeneca’s MedImmune group reached out to McLellan to develop an antibody based on his research. After testing over 1,500 variants of an antibody, AstraZeneca and McLellan landed on Beyfortus, which entered the clinic in 2014. Sanofi came aboard in 2017, striking an alliance with AstraZeneca to jointly develop the drug.

That basic research led to a key difference between Beyfortus and Synagis, Heinrichs said. While both antibodies target the F protein, they hit different parts. Beyfortus targets a spot called Site Zero, which stops the prefusion form from changing shape.

“It prevents the virus from entering into the cell at the very beginning, so it blocks infection,” Heinrichs said.

AstraZeneca scientists tweaked other parts of the antibody to boost its half-life, meaning how long it lasts in the body. Beyfortus’ half-life went from a few weeks to 70 days in infants, Heinrichs said, which means one injection can last all RSV season.

Those differences could open Beyfortus up for use in all newborns, Heinrichs said. Synagis has been limited to the highest-risk population — those infants who had extremely premature births or have heart or lung defects — because of its price and monthly dosing requirement.

Sanofi touts durability, flexibility

Synagis has long been the only option to protect infants for decades, but Sanofi and AstraZeneca are already prepping for a looming challenger. Pfizer expects an approval decision in August for its vaccine in pregnant women to protect newborns. Pfizer’s shot was 82% effective at preventing severe illness in newborns for three months after birth.

Sanofi’s Heinrichs said Beyfortus has a couple of advantages over a vaccine.

One is protecting the highest-risk infants. Maternal vaccines rely on transferring antibodies from the mother to the newborn through the placenta. That can be a “major problem” for preterm births because those antibodies don’t cross the placental barrier until very late in the pregnancy, Heinrichs said.

“Those preterm infants that are really, really vulnerable to RSV disease typically would not be protected by maternal vaccination,” he said.

A second question is durability. While Pfizer’s vaccine shows high efficacy against hospitalization, that was only for three months after birth. Clinical results show protection wanes over time. A baby born in June, for instance, would have “very little” RSV antibodies left when RSV season starts in November, Heinrichs said.

Sanofi imagines Beyfortus could be administered in the hospital for babies born during RSV season and given as an injection during routine pediatrician visits for those born outside the season.

Sanofi and AstraZeneca are now waiting on a Centers for Disease Control and Prevention advisory group meeting scheduled for August 3, which will discuss how Beyfortus should be used. They plan to launch Beyfortus in the US for this next RSV season, if possible, Heinrichs said.

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