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.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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