Novavax plummets after another phase 3 RSV study miss, this time in infants

Once described as having the potential to become “the largest selling vaccine in the history of vaccines,” Novavax’s fusion protein nanoparticle shot against respiratory syncytial virus has missed another phase 3 trial, causing the company’s stock price to lose about two-thirds of its remaining value in premarket trading.

In September 2016, Novavax’s shares plunged after a placebo-controlled study of nearly 12,000 adults, age 60 and over, failed to meet its efficacy objectives in preventing RSV-related disease in the lower respiratory tract. The company cut 30% of its workforce two months later.

Now, after moving forward with an $89.1 million grant from the Bill & Melinda Gates Foundation, the recombinant RSV vaccine ResVax flunked its primary endpoint in the maternal immunization of infants. The four-year study of 4,600 pregnant women, with the vaccine administered in the third trimester, aimed to see if immunity could be passed on after birth and through at least the first 90 days of life.

While the well-tolerated vaccine was only 39% effective against the study’s primary objective of preventing medically significant RSV-related lower respiratory tract infections, Novavax pointed to secondary data showing that all-cause LRTI hospitalizations were reduced by 25%, and that it was 44% effective against RSV-related LRTI hospitalizations.

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RSV is the leading cause of infant hospitalizations in the U.S., and is second only to malaria as a cause of infant deaths worldwide, with lifelong susceptibility being common, according to Novavax. In May 2018, executives had said the vaccine could attain $1.5 billion in sales—with half coming from the U.S., and before adding potential revenues from middle-income markets and low-income countries—and that the company had begun taking precommercialization steps.

Describing the new study’s secondary objective numbers as the first phase 3 efficacy seen from any RSV vaccine—and that “exploratory endpoints and post-hoc analyses” still suggest a potential to improve global health—Novavax said its next steps are to meet with U.S. and European regulators to discuss licensure pathways.

“We are very encouraged that the Novavax maternal RSV vaccine reduced severe RSV hypoxemia by 60% in the first months of life and believe this vaccine has great potential for reducing RSV-associated deaths in young babies,” Keith Klugman, director of the Gates Foundation’s pneumonia program, said in a statement. The 60% figure comes from a pre-specified exploratory analysis and includes additional data from hospitalization records, while the study’s secondary efficacy endpoint of the same measure reached 48%.

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Progress against RSV has also been slow on the therapy side, with Johnson & Johnson revealing late last year that it took a $630 million hit after its phase 2b trials of its oral lumicitabine treatment were put on hold last August. The impairment charge followed J&J’s $1.75 billion takeover of the antiviral developer Alios, with lumicitabine, also known as AL-8176, serving as the lead drug in the deal.

In an SEC filing last October, J&J said it would “reassess the carrying value of the AL-8176 in-process research and development asset,” and will “monitor the remaining $900 million intangible asset for further impairment.”