DUBLIN – The European Medicines Agency (EMA) has reiterated its support for Astrazeneca plc’s Vaxzevria COVID-19 vaccine, following an interim analysis of a data review, which the agency’s Committee on Human Medicinal Products (CHMP) has conducted over the past two weeks.

To take account of variations between different counties and between different time points, the CHMP developed a data model to assess the benefits of the vaccine for different age groups in conditions of low (55 cases per day per 100,000 population), medium (401 cases per day per 100,000) and high (886 cases per day per 100,000) background infection rates. Benefit was assessed on three parameters:

  • the number of hospitalizations avoided,
  • the number of intensive care unit admissions avoided,
  • and the number of deaths avoided.

It was weighed against the age-adjusted risk vaccine recipients developing of blood clots with low platelet counts (also called thrombosis with thrombocytopenia syndrome), a rare but life-threatening side-effect of the Astrazeneca vaccine.

Peter Arlett, EMA

“If we look at the different benefit scenarios and look at the different infection rates, we can see that for all age categories, benefits occur in some scenarios, and on that basis, the committee has clearly concluded that the overall benefit-risk remains positive,” Peter Arlett, head of the data analytics and methods task force at the EMA, told reporters during a media briefing on April 23. “The vaccines, in all scenarios, prevent hospitalizations, prevent admissions to intensive care units, prevent deaths. Those benefits increase with age; those benefits increase with higher infection rates.”

Noel Wathion, EMA

There are no grounds to limit the vaccine to older adults only, said Noël Wathion, deputy executive director at the EMA, even though some countries are doing so, while others, notably Denmark, have dropped the vaccine completely. “It is too early at this moment in time to consider any particular regulatory change. In order to do so, we need to have much more evidence in terms of benefit and risk, which then have to be weighed against each other. That is the normal process in terms of how regulatory changes work,” he said.

Even though clotting with thrombocytopenia appears to be more common in women than men, based on the data reported to date, the committee was unable to assess the data in terms of gender, as just a subset of member states were able to submit gender-stratified data in the available time frame. That may change in the future, and the committee is open, Wathion said, to fine-tuning its conclusions should additional data support such a move.

The data still favor the use of the Astrazeneca vaccine in younger adults, but the evidence is not as firm as it is for older adults. “There is a significant benefit in terms of avoiding hospitalization across all age groups,” Arlett said. “The data on ICU admissions and on deaths – there are too few events in the younger age group to show that benefit, but for hospitalization the data are very clear,” he said.

Marco Cavaleri, EMA

EMA officials remained cautious about attributing the clotting problems seen with the Astrazeneca vaccine in Europe and in the U.S. with the COVID-19 vaccine from Johnson & Johnson Co., of New Brunswick, N.J., to a class effect. Both are based on inactivated recombinant adenoviral vectors, and the same issue has not emerged with the two approved mRNA COVID vaccines, from Pfizer Inc and Biontech SE, and from Moderna Inc., despite their widespread administration. “We don’t know yet what is the mechanism behind these rare events. We are, right now, in the process of starting a number of investigations that hopefully will clarify at the soonest what really is the mechanism that is causing them,” said Marco Cavaleri, head of biological threats and vaccines strategy at the EMA.

The present analysis adds more weight to the recommendations of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), which earlier this month recommended continued use of the vaccine but an update to the product information to take account of the risk of cerebral venous sinus thrombosis and abdominal splanchnic vein thrombosis. But it remains the responsibility of individual EU member states to decide where the vaccine fits into their respective national vaccination campaigns. “We hope that this work will support the member states in their decision on how to optimize the use of vaccines based on local infection rates,” Arlett said.

The CHMP also approved adjustments at manufacturing facilities in Belgium and Spain, which will boost the production of Pfizer-Biontech’s and Moderna’s respective mRNA vaccines. It approved an increase in batch size and associated process scale-up at Pfizer’s plant in Puurs, Belgium, and a new filling line at Moderna’s fill-finish facility in Rovi, Spain.

Five new drug approvals

At its April meeting, the CHMP also recommended five new drug approvals, as well as two generics and one product submitted under the hybrid approval pathway. Among those that will soon formally gain European approval are Enspryng (satralizumab), an interleukin-6 (IL-6) receptor inhibitor developed by Roche Holding AG for adults with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). It gained FDA approval in June 2020.

Ballerup, Denmark-based Leo Pharma A/S got a nod for Adtralza (tralokinumab), an IL-13 inhibitor, for treating atopic dermatitis. A U.S. review is still ongoing, but a decision is expected in the current quarter. The Danish firm in-licensed the antibody from Cambridge, U.K.-based Astrazeneca five years ago.

A third antibody, Evkeeza (evinacumab), which Regeneron Pharmaceuticals, Inc., of Tarrytown, N.Y., developed for treating patients with homozygous familial hypercholesterolemia, also received a positive recommendation. The antibody, which targets angiopoietin-like 3 (ANGPTL3), gained FDA approval in February.

Two new small-molecule drugs received positive votes. Koselugo (selmetinib), a Mek inhibitor developed by Astrazeneca, is recommended for approval for treating pediatric patients with the rare genetic condition neurofibromatosis type 1 plexiform neurofibromas, which is characterized by the growth of benign tumors along nerve sheaths throughout the body. Astrazeneca and its U.S. partner Merck & Co. Inc., of Kenilworth, N.J., gained FDA approval for the drug 12 months ago.

Celgene Europe BV, now part of New-York-based Bristol Myers Squibb Co., received a positive vote for Onureg (azacitidine), an oral form of the venerable chemotherapy drug, as a maintenance therapy in acute myeloid leukemia. It, too, gained FDA approval last year.