AstraZeneca's vaccine hit its first roadblock with Indian regulators. Will lingering doubts derail its plans elsewhere?
British drugmaker AstraZeneca is already running behind early competitors in the hunt for a Covid-19 vaccine with interim data that have received less-than-stellar feedback. With those data in hand, India has said “no thanks” to an early approval for the shot, potentially setting the stage for even more setbacks.
On Tuesday, Indian regulators refused to grant AstraZeneca’s adenovirus-based Covid-19 vaccine an emergency use authorization based on a dearth of adequate safety and efficacy data, Reuters reported, citing local broadcaster NDTV.
India’s early no comes just hours after AstraZeneca’s interim data were published in The Lancet unveiling expanded safety data and further breaking down the 70% average efficacy figure that has confounded analysts and cast doubts on whether the vaccine will ever compete with more effective competitors from Pfizer and Moderna — and maybe others yet to read out.
In a note to clients Wednesday breaking down the data, SVB Leerink analyst Andrew Berens was less than kind to the early readout, despite one of the dosing regimens in three Phase III trials — a half-dose first shot followed by a full-dose primer — hitting 90% efficacy.
“The publication highlights a number of variances in the dosing regimens utilized in these trials that could make it difficult for the regulatory agencies to have confidence in the optimum dosing protocol for full approval without additional studies,” Berens wrote.
For one, the big variability between the low-dose/high-dose combo and the high-dose/high-dose regimen—which only posted 62% efficacy across three pooled trials did little to inspire confidence. The more effective regimen could be enough to spur regulators’ interest, but there are problems with that data as well, Berens said; significantly fewer patients received that regimen and those who did typically skewed younger.
Meanwhile local trial protocols varied widely, Berens noted, with patients receiving booster shots at different intervals across study sites. On a call with media Tuesday, AstraZeneca’s executive VP of biopharma R&D Mene Pangalos said that variability in booster timing wasn’t necessarily a bad thing: With global demand and limited supplies, patients could be forced to wait on a second shot in the future.
Meanwhile, Berens also cast doubt on the shot’s manufacturing, which appeared to show variable strengths across different production sites. AstraZeneca argued those differences were within a comfortable range given the geographically disparate supply chain, but Berens begged to differ.
“We believe this could be a detriment when attempting to gain regulatory approval as the manufacturing process may not be uniform and tighter release specifications for vaccines are generally preferred,” he wrote.
Manufacturing had been a boon for AstraZeneca in comparison to its early mRNA-based vaccine competitors from Pfizer and Moderna. For one, AstraZeneca’s shot can be stored and distributed indefinitely at room temperature while Pfizer’s shot, in particular, requires strenuous cold-chain logistics that could make it hard to distribute in developing countries.
With those questions in mind, India’s big no is both an immediate surprise — the country and its vaccine giant, the Serum Institute of India, have been churning out millions of doses of the shot for local and international use — but could be a sign of things to come as AstraZeneca faces rolling review in the EU, UK and elsewhere.
The drugmaker on Tuesday said it was still awaiting US data and would withhold an FDA filing in the meantime.
AstraZeneca can also lean on its relatively clean safety profile — one of the highlights from its Lancet publication. Across four pooled studies encompassing 20,000 patients, AstraZeneca’s vaccine saw 79 severe events compared with 89 events in the control arms. AstraZeneca reported three cases of transverse myelitis, which causes swelling in the spinal cord, two of which were deemed unrelated to the vaccine.
The third case, which caused AstraZeneca’s vaccine to go on clinical hold earlier this year, was determined to be “possibly related” to the shot, Berens wrote. That black mark aside, the vaccine resulted in no hospitalizations or deaths in the three trials pooled for efficacy while there were 10 hospitalizations and one death in the control arms.
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