The FDA and the CDC have jointly recommended a temporary pause in the further rollout of Johnson & Johnson Co.’s COVID-19 vaccine while they investigate six rare clotting cases in adults ages 18 to 48.
“The time frame will depend obviously on what we learn in the next few days. However, we expect it to be a matter of days for this pause,” acting FDA Commissioner Janet Woodcock told reporters during a media briefing hosted by the two agencies.
The CDC is convening a meeting of its Advisory Committee on Immunization Practices April 14 to further review the six cases of cerebral venous sinus thrombosis (CVST), which coincided with thrombocytopenia or low levels of blood platelets. “We are committed to an expeditious review of the available information and to an aggressive outreach to clinicians so that they can diagnose, treat and report,” said Anne Schuchat, principal deputy director of the CDC.
Problems with the vaccine first surfaced last week, in a brief report issued April 9 by the EMA’s Pharmacovigilance Risk Assessment Committee, which referenced “thromboembolic events” – blood vessel blockage due to clot formation – in individuals who had received COVID-19 Vaccine Janssen. The EMA committee was at that point aware of four cases, one of which occurred in a clinical trial and three of which had occurred during the U.S. rollout. One of those four proved fatal.
The total number of identified cases is now six among 6.8 million people who have so far received J&J’s single-shot COVID-19 vaccine, which is based on a recombinant inactivated adenovirus 26 vector encoding the SARS-CoV-2 protein. It received emergency use authorization from the FDA on Feb. 27. “I cannot speculate about how many more we will learn of – hopefully, it’s just going to be a few,” said Peter Marks, director of the FDA’s Centre for Biologics Evaluation and Research (CBER). In the meantime, J&J, of New Brunswick, N.J., has decided to delay the rollout of its vaccine in Europe. It had been recommended for conditional approval on March 11.
CVST arises from the formation of blood clots in the dural venous sinuses, blood vessels which drain blood from the brain. It is characterized by very severe headache and by symptoms associated with stroke. It has a background rate of two to 14 cases per million per year, Marks said, but that is in the setting of normal blood platelet counts.
“The real thing that is so notable here is not just the cerebral venous sinus thrombosis or the thrombocytopenia – those two things can occur – it’s their occurrence together that makes a pattern, and that pattern is very, very similar to what was seen in Europe with another vaccine, so I think we have to take the time to make sure we understand this complication and we address it properly,” Marks said.
Managing the problem can be risky, given the difficulty in identifying it in the first place. “The issue here with these types of blood clots is that if one administers the standard treatment that we as doctors have learned to give for blood clots, one can actually cause tremendous harm or the outcome can be fatal,” Marks said. The cause of the problem is still unclear. The working hypothesis suggests it may arise from a rare autoimmune attack on patients’ platelets, but a definitive mechanistic understanding has not been established as yet.
No such problems have been associated with the 180 million doses of mRNA vaccines that have been administered in the U.S. so far. But Cambridge, U.K.-based Astrazeneca plc’s vaccine, which is based on a recombinant inactivated chimp adenovirus, was associated with 62 cases (as of March 22) of CVST combined with thrombocytopenia, as well as 24 cases of another clotting disorder, splanchnic vein thrombosis, which occurs in abdominal blood vessels. Eighteen deaths have occurred so far, and the issue has prompted national authorities in several countries to limit administration of the virus to older people.
“I hesitate to call it a class effect. It’s plainly obvious to us already that what we’re seeing with the Janssen vaccine looks very similar to what was being seen with the Astrazeneca vaccine,” Marks said. It is still difficult to draw any general conclusions about who is most at risk of developing the problem, given its rarity. “At this time, it’s not clear that there’s any association with the oral contraceptive pill,” Marks said. That had been suggested due to an apparent gender imbalance in the distribution of cases in Europe.
Sputnik V approved in India
J&J’s single-shot vaccine is based on an adenovirus 26 (Ad26) vector, which is also employed in the Sputnik V vaccine developed by the Moscow-based Gamaleya National Centre of Epidemiology and Microbiology. The latter product, which received regulatory approval in India earlier today, also includes a recombinant Ad5 vector as part of a heterologous prime-boost regimen. Given the issues seen with Astrazeneca plc’s COVID-19 vaccine and now with J&J’s vaccine, it is difficult to see how Sputnik V will not cause similar problems, if it has not done so already. However, Russian officials studiously avoided addressing the question during a media briefing April 13 to discuss their plans for ramping up production in India.
The Russian Direct Investment Fund (RDIF) has entered partnerships with five manufacturers so far, including Gland Pharma, Hetero Biopharma, Panacea Biotec, Stelis Biopharma and Virchow Biotech. “We will shortly announce several more,” RDIF CEO Kirill Dmitriev told reporters on a media briefing. The aim is to achieve a monthly run rate of more than 50 million doses by the end of the summer, and the RDIF is providing working capital to some of its partners to enable them to ramp up production. Russia has also entered agreements with producers in South Korea, Brazil, China, Saudi Arabia and Turkey. The vaccine is now approved in 60 countries, which have a combined population of 3 billion people. So far, it has been administered to more than 2 million people worldwide, however.
Shares in several other COVID-19 vaccine makers rose on the J&J news: Novavax Inc. (NASDAQ:NVAX) was up by as much as 14.4%; Moderna Inc. (NASDAQ:MRNA) hit a peak of $152.11, a gain of 9.1% on its previous close; Biontech SE (NASDAQ:BNTX) gained as much as 7.6%; and Curevac AG (NASDAQ:CVAC) was at one point up by 5.6%.