AZN/Oxford Vax Results "Embellished" (Analyst)

UPDATED: AstraZeneca, Oxford on the defensive as skeptics dismiss 70% average efficacy for Covid-19 vaccine
Amber Tong
Editor

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.



But investors apparently aren’t happy with the average efficacy figure, sending AstraZeneca’s shares $AZN down 0.98% in Nasdaq pre-marketing trading and 1.73% in London.

Jefferies analyst Michael Yee summed up the sentiments: “We wonder which countries and populations would get the lower efficacy vaccine.”

So how do the data stack up?

AstraZeneca and Oxford are basing their interim analysis on 11,636 volunteers from two trials conducted in the UK and Brazil, each with 10,000-plus participants. In total, there were 131 cases of Covid-19 — 30 in the vaccine group and 101 in the placebo arm.

While both trials compared one dose with a prime-boost approach, the UK study broke it down further and tested a dosing regimen in which the vaccine, dubbed AZD1222 or ChAdOx1 nCoV-19, was first given as a half dose then followed by a full dose. That cohort (n=2,741) showed the best response, with a 90% difference from placebo, while the 8,895 who were given two full doses only saw 62% efficacy.

It isn’t clear how many volunteers in each of these subgroups — either receiving vaccine or placebo — developed Covid-19. AstraZeneca said all results were statistically significant (p<=0.0001).

Pfizer and BioNTech reported that among 170 Covid-19 cases in their 44,000-person trial, 162 cases were in the placebo group and 8 in the vaccine group. Moderna’s interim readout, on the other hand, had a 90-5 split between the placebo and vaccine arms.

When asked at an online press conference why an initial half dose would lead to a better response, Andrew Pollard — chief investigator of the Oxford vaccine trial — said they could not fully explain it but posited it had to do with “priming the immune system differently” and “setting it up better to respond.” Others have speculated that the anti-vector immunity was the chief culprit.

For him, no matter the reason, the unexpected upside of the half-then-full dose regimen is good news.

“(I)f this dosing regime is used, more people could be vaccinated with planned vaccine supply,” he said in a statement.

There is, however, no guarantee that regulators would OK that particular regimen in their first review, especially given that it was only given to a small subset of volunteers. Ruud Dobber, president of AstraZeneca US and EVP of biopharmaceuticals, told CNBC:

We believe and we think that the regulator’s will focus on this half-dose/ full-dose regimen, but of course it’s in the hands of the regulators.

He also highlighted that no hospitalizations or severe Covid-19 were reported in the vaccine group, but AstraZeneca didn’t disclose the number of such instances in the placebo arm.

That all struck Geoffrey Porges as “premature and insufficient.” The SVB Leerink analyst has some harsh words for AstraZeneca, describing their subgroup analysis as an attempt to “embellish.”

“The company is likely to be roundly criticized today for their disclosure, since the safety disclosure simply state that ‘no serious safety events related to the vaccine have been confirmed’ which is hardly reassuring. They did not disclose any information about any actual safety events,” he wrote, adding that there was no breakdown for subpopulations such as the elderly, high risk or minority populations. “The suggestion by the inventors that the small sample given the lower priming dose was evidence of superior efficacy only brings discredit to the program.”

Given the apparent lack of representation of key groups and previous occurrence of severe safety events that resulted in weekslong clinical hold, Porges predicted the FDA will never approve the vaccine.

Notably, while it does have a deal to supply the US with 300 million doses, the bulk of AstraZeneca’s vaccines are slated to go to what’s called “rest of world” regions, many of them being less developed countries.

Experts and companies have long argued that multiple safe and effective vaccines would be needed to vaccinate the global population. AstraZeneca has lined up capacity to produce 3 billion doses of its vaccine candidate starting in 2021, giving it the largest inventory out of the frontrunning players.

The vaccine can be stored and transported at 2 to 8 degrees Celsius or 36 to 46 degrees Fahrenheit for at least six months, lowering the handling barrier compared to mRNA jabs from Pfizer/BioNTech and Moderna. The former needs to be kept at -70 degrees Celsius and can only stay in 2 to 8 fridges for seven days; the latter can stay stable at -20 degrees for up to 6 months days, 2 to 8 degrees for up to 30 days, and at room temperature for up to 24 hours.

AstraZeneca has promised not to profit off the vaccine at least initially, charging just a few dollars for each shot. By comparison, the supply deals Pfizer and BioNTech have struck with the US (where they have just filed for emergency use) and the EU price their vaccine at $18.34 or $19.5 per dose, while Moderna’s US per-unit price works out to $10.

“(T)he vaccine’s simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available, supplying hundreds of millions of doses on approval,” AstraZeneca CEO Pascal Soriot added.