Following the company’s COVID-19 manufacturing misstep, Emergent Biosolutions Inc. continued its struggle to rebalance as top-line data from a phase III study it participated in failed to hit its primary endpoints with statistically significant results.
The data showed that adding anti-SARS-CoV-2 hyperimmunoglobulin to standard of care, inclusive of remdesivir, for hospitalized adult COVID-19 patients with symptoms for less than 12 days failed to provide clinical benefit when compared to standard of care plus placebo.
The global, multicenter double-blind, placebo-controlled randomized study assessed the safety and efficacy of four immunoglobulin candidates, the SARS-CoV-2 immune globulin intravenous (human) (COVID-HIG) plus standard of care. COVID-HIG, which Emergent said it would continue to develop in ongoing trials, including as a treatment for outpatients at a high risk of progression to severe disease, comprises a concentrated solution of antibodies for neutralizing SARS-CoV-2. The antibodies come from plasma donated by healthy subjects who have recovered from COVID-19.
Four companies supplied HIG material for the study, tabbed the Inpatient Treatment with Anti-Coronavirus Immunoglobulin, or INSIGHT-013, including Emergent, CSL Behring, Grifols SA, of Barcelona, and Takeda Pharmaceutical Co. Ltd. The clinical trial was funded by the National Institute of Allery and Infectious Diseases, part of the U.S. NIH.
Grifols said it would evaluate a subcutaneously delivered anti-SARS-CoV-2 hyperimmune globulin for asymptomatic patients in Spain. The company is also part of a Spanish clinical trial testing convalescent plasma as an early treatment for those patients with mild or moderate COVID-19 who are not hospitalized.
In the manufacturing misstep, Emergent identified a single batch of a drug substance that did not meet specifications and quality standards at its Bayview facility in Baltimore while reviewing creation of Johnson & Johnson’s COVID-19 vaccine. The batch had not advanced to the filling and finishing stages by the time it was identified and was then discarded.
J&J said the loss of the 15 million batch of the vaccine was a result of human error. The company had committed 100 million doses to the U.S. government for the first half of 2021. Since the vaccine is a single dose, the batch is the equivalent of 30 million doses of the mRNA vaccines from Moderna Inc. or Pfizer Inc.-Biontech.
SVB Leerink analysts on April 1 noted that production at the facility has stopped while the FDA inspects and validates procedures before allowing it to ramp up again. The delay could be open-ended, the analysts added, with the potential to last for weeks “or theoretically months depending on whether any remediation” is necessary.
“Lot release failures are not uncommon for biological products, and the basis for those failures is rarely disclosed,” the analysts continued. “Since mRNA products are manufactured using synthetic chemical processes, we regard them as more transferable, more scalable and less vulnerable to process or lot failures (provided the chemical synthetic process is tightly controlled) than biologics.”
J&J said it is sending in “additional experts” in manufacturing and technical operations and quality to the manufacturing site to “supervise, direct and support all manufacturing” of its vaccine. Emergent noted that discarding a batch of bulk drug substance, “while disappointing, does occasionally happen during vaccine manufacturing, which is a complex and multistep biological process.”
“While a disappointing update, we see the near-term risk to the business as potentially limited given the large majority of the value of its current contracts is guaranteed up front,” wrote J.P. Morgan analyst Jessica Fye on April 1. “However, the headlines bring up further questions about the likelihood of the extensions on its COVID-19 vaccine contracts materializing and could have a reputational effect on [Emergent’s] ability to win other CDMO business, which we see as key to performance beyond 2021.”
While the U.S. markets were closed April 2, Gaithersburg, Md.-based Emergent’s stock (NYSE:EBS) took a hit the previous day when news of the mistake broke. Shares closed 13% lower at $80.46 each on April 1.