An­a­lysts as­sess fall­out af­ter As­traZeneca halts PhI­II Covid-19 vac­cine dos­ing to probe a pos­si­ble se­ri­ous ad­verse event

In­ves­ti­ga­tors at As­traZeneca have or­dered a halt to dos­ing their close­ly-watched Covid-19 vac­cine in or­der to probe a po­ten­tial­ly se­vere ad­verse event — re­port­ed­ly in­volv­ing in­flam­ma­tion of the spinal cord — suf­fered by one of the tri­al par­tic­i­pants.

In a state­ment out Tues­day evening, a spokesman for the phar­ma gi­ant told End­points News that the study had been put on hold to in­ves­ti­gate an ill­ness. Lat­er Tues­day, they sent a re­vised state­ment, which not­ed that the halt is vol­un­tary, not or­dered by reg­u­la­tors. It reads:

As part of the on­go­ing ran­domised, con­trolled glob­al tri­als of the Ox­ford coro­n­avirus vac­cine, our stan­dard re­view process was trig­gered and we vol­un­tar­i­ly paused vac­ci­na­tion to al­low re­view of safe­ty da­ta by an in­de­pen­dent com­mit­tee. This is a rou­tine ac­tion which has to hap­pen when­ev­er there is a po­ten­tial­ly un­ex­plained ill­ness in one of the tri­als, while it is in­ves­ti­gat­ed, en­sur­ing we main­tain the in­tegri­ty of the tri­als. In large tri­als ill­ness­es will hap­pen by chance but must be in­de­pen­dent­ly re­viewed to check this care­ful­ly. We are work­ing to ex­pe­dite the re­view of the sin­gle event to min­imise any po­ten­tial im­pact on the tri­al time­line. We are com­mit­ted to the safe­ty of our par­tic­i­pants and the high­est stan­dards of con­duct in our tri­als.

The spokesman did not say what ill­ness was in­volved, but the New York Times re­port­ed that the halt was trig­gered by a case in the UK of trans­verse myelitis, an in­flam­ma­tion of the spinal cord that can in­ter­rupt mes­sages that spinal cord nerves trans­mit. Ac­cord­ing to Johns Hop­kins, “it is char­ac­ter­ized by symp­toms and signs of neu­ro­log­ic dys­func­tion in mo­tor and sen­so­ry tracts on both sides of the spinal cord.”

The con­di­tion can be trig­gered by a va­ri­ety of things, in­clud­ing vac­ci­na­tions.

As­traZeneca’s shares slid 6% af­ter the bell on Tues­day, a sharp drop for a Big Phar­ma of that size. Shares of Mod­er­na and BioN­Tech, the two mR­NA lead­ers in Phase III, each jumped 5%.

This is the first such pause in the fren­zied race to get a Covid-19 vac­cine to the goal line. And the in­ter­rup­tion on a Covid-19 leader like this trig­gered head­lines world­wide. As­traZeneca, like the rest of the lead­ing de­vel­op­ers work­ing on a pan­dem­ic vac­cine, has been bar­rel­ing ahead in­to late-stage piv­otal work on a jab for the coro­n­avirus that has dis­rupt­ed the world. But at every quick step, ex­ecs at the multi­na­tion­al have al­so re­peat­ed­ly as­sured all in­volved that they will not hes­i­tate to slow things down if war­rant­ed.

The next big ques­tion is how long As­traZeneca’s vac­cine could be on pause and whether there could be a spillover in­volv­ing oth­er vac­cine mak­ers.

An­drew Berens at SVB Leerink put it this way, siz­ing up the im­pact if it is trans­verse myelitis:

AZN’s vac­cine study may be post­poned by weeks to months, as the safe­ty data­base is scru­ti­nized and tri­al pro­to­cols re­vised. Fur­ther, this AE could have the po­ten­tial to slow down vac­cine de­vel­op­ment more broad­ly. Trans­verse myelitis has not been de­fin­i­tive­ly linked to any com­mer­cial vac­cines, but it has been shown to be re­lat­ed to nat­ur­al virus in­fec­tion, and a few cas­es of trans­verse myelitis were de­scribed af­ter ad­min­is­tra­tion of the MMR, vari­cel­la, and he­pati­tis B vac­cines (the mech­a­nis­tic ev­i­dence was de­ter­mined to be weak per the In­sti­tute of Med­i­cine, cur­rent­ly the Na­tion­al Acad­e­my of Med­i­cine).

Safe­ty is­sues — par­tic­u­lar­ly when they could be tied to a se­ri­ous ad­verse event — loom par­tic­u­lar­ly large here. Any sug­ges­tion of a safe­ty prob­lem could raise con­cerns for all in­volved, pos­ing added prob­lems in the event they pro­voke pub­lic re­sis­tance to a shot. And there are po­lit­i­cal im­pli­ca­tions as well. As Pres­i­dent Trump has promised a vac­cine by year’s end, or even soon­er, the top vac­cines have a shot at a snap OK. Safe­ty is­sues would put a vac­cine fur­ther be­hind in the line.

Jef­feries’ Michael Yee was quick to pick up on that as­pect, writ­ing:

While we see this event as more of a short- to medi­um-term top­ic for de­bate, we do be­lieve these vac­cines will like­ly end up be­ing dif­fer­en­ti­at­ed on ef­fi­ca­cy and safe­ty in their Phase II­Is, which could dri­ve opin­ions on which is “best” and even­tu­al mar­ket up­take.

At our lat­est count, we in­clude the As­traZeneca vac­cine in 3rd place among 29 com­pa­nies in or near the clin­ic, right be­hind the mR­NA lead­ers at Pfiz­er/BioN­Tech and Mod­er­na. They’ve been work­ing with $1.2 bil­lion in pub­lic fi­nanc­ing for this work, with the Phase III get­ting un­der­way in Ju­ly. In­ves­ti­ga­tors plan to re­cruit 30,000 pa­tients in the US and 50,000 world­wide as they look for a broad pa­tient group to test safe­ty and ef­fi­ca­cy.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot (AP Images)

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

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.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

A poll sug­gests vac­cine da­ta boost­ed Pfiz­er's pub­lic im­age, but oth­er da­ta point to long road ahead

For much of the pharmaceutical industry, the pandemic presented an opportunity: to prove their value to the world and turn public opinion around on a business much of the country had come to disdain.

That theory — that helping pull the country from a pandemic could neutralize years of anger over high drug prices — was put to its biggest test this month, as three different drugmakers announced data from their Covid-19 vaccines, offering the first major evidence that industry-built inoculations could turn the tide of the outbreak in the US.