Covid-19 roundup: RE­COV­ERY tri­al halts re­cruit­ment for colchicine study af­ter find­ing ‘no con­vinc­ing ev­i­dence’; Italy blocks As­traZeneca vac­cine ship­ment meant for Aus­tralia

It may be the end of the road for colchicine, an in­ex­pen­sive oral an­ti-in­flam­ma­to­ry drug com­mon­ly used to treat gout, as a po­ten­tial Covid-19 treat­ment — at least in hos­pi­tal­ized pa­tients.

The UK’s RE­COV­ERY tri­al put out the word on Fri­day that it’s halt­ing en­roll­ment in its colchicine study af­ter a da­ta mon­i­tor­ing com­mit­tee saw “no con­vinc­ing ev­i­dence that fur­ther re­cruit­ment would pro­vide con­clu­sive proof of worth­while mor­tal­i­ty ben­e­fit ei­ther over­all or in any pre-spec­i­fied sub­group.”

In a pre­lim­i­nary analy­sis of 11,162 pa­tients ran­dom­ized to re­ceive ei­ther colchicine or stan­dard care alone, there was no sig­nif­i­cant dif­fer­ence in the pri­ma­ry end­point of 28-day mor­tal­i­ty, ac­cord­ing to re­searchers. The mor­tal­i­ty rate was 20% in the colchicine group ver­sus 19% in the usu­al care group. The fi­nal re­sults will be pub­lished “as soon as pos­si­ble,” ac­cord­ing to a state­ment.

The RE­COV­ERY tri­al was es­tab­lished to test a range of po­ten­tial treat­ments for Covid-19. Re­cruit­ment to all the oth­er treat­ment arms — in­clud­ing as­pirin, baric­i­tinib, Re­gen­eron’s an­ti­body cock­tail, and (in se­lect­ed hos­pi­tals) di­methyl fu­marate — will go forth as planned.

“We do large ran­domised tri­als to es­tab­lish whether a drug that seems promis­ing in the­o­ry has re­al ben­e­fits for pa­tients in prac­tice,” Ox­ford Uni­ver­si­ty and joint chief in­ves­ti­ga­tor Mar­tin Lan­dray said in a state­ment. “Un­for­tu­nate­ly, colchicine is not one of those.”

The news comes just over a month af­ter Mon­tre­al re­searchers read out some con­tro­ver­sial da­ta on colchicine’s ef­fect as a Covid-19 treat­ment. While that study al­so failed its pri­ma­ry end­point, re­searchers said the drug “re­duces the com­pos­ite rate of death or hos­pi­tal­iza­tion” in non-hos­pi­tal­ized pa­tients.

Out of 2,235 pa­tients in the colchicine group, 104 had been hos­pi­tal­ized or died; among 2,253 in the place­bo co­hort, 131 re­port­ed those events. That trans­lates to a 4.7% event rate ver­sus 5.8% on the pri­ma­ry end­point — or an odds ra­tio of 0.79 — with a p-val­ue of 0.08. Five pa­tients died in the colchicine arm, ver­sus nine in the place­bo group. On the sec­ondary end­point, 11 pa­tients tak­ing colchicine re­quired me­chan­i­cal ven­ti­la­tion while 21 who were giv­en place­bo did.

But if you look on­ly at the 4,159 pa­tients with PCR-con­firmed Covid-19, in­ves­ti­ga­tors wrote, the dif­fer­ence widens slight­ly to 4.6% ver­sus 6.0% and the 0.75 odds ra­tio be­comes sta­tis­ti­cal­ly sig­nif­i­cant (p=0.04).

Lan­dray com­ment­ed that it was a “trav­es­ty” that in­ves­ti­ga­tors in the tri­al had stopped en­roll­ment with on­ly 75% of pa­tients, adding that it re­sult­ed in in­con­clu­sive re­sults and un­cer­tain­ty. — Nicole De­Feud­is 

Italy blocks As­traZeneca vac­cine ship­ment meant for Aus­tralia

The As­traZeneca/Ox­ford vac­cine roll­out has run in­to yet an­oth­er speed bump.

As the British drug­mak­er prepped a vac­cine ship­ment for Aus­tralia of about 250,000 dos­es, Italy de­cid­ed to pre­vent the de­liv­ery from leav­ing its bor­ders, per a Fi­nan­cial Times re­port. It’s the first such in­ter­ven­tion in vac­cine ex­ports since the Eu­ro­pean Union in­tro­duced new rules gov­ern­ing such ship­ments out­side the bloc in late Jan­u­ary.

Per the FT re­port, the EU had the pow­er to ob­ject to Italy’s move and block their ef­fort, but did not do so. And ear­ly Fri­day morn­ing, France backed Italy’s plan to stop the ship­ment head­ed to Aus­tralia.

The con­tro­ver­sial ex­port plan was put in­to place by the EU in the wake of As­traZeneca say­ing it wouldn’t be able to pro­vide the amount of dos­es pledged in its con­tracts a lit­tle over a month ago. Their hope is to force com­pa­nies to dis­close ex­port plans, the FT cit­ed Eu­ro­pean of­fi­cials as say­ing, as the bloc seeks to re­assert con­trol of dos­es man­u­fac­tured in­side its bor­ders.

Sev­er­al coun­tries had been ex­empt­ed from the plan, al­low­ing for As­traZeneca shots to be able to flow to poor­er na­tions and those with­out their own pro­duc­tion ca­pa­bil­i­ties. EU of­fi­cials drew harsh crit­i­cism, how­ev­er, af­ter in­clud­ing the UK on the ex­emp­tion list de­spite leav­ing off oth­er in­dus­tri­al­ized na­tions like the US and Japan.

Fri­day’s de­vel­op­ments fol­low a rocky road for the As­traZeneca/Ox­ford vac­cine. Though Britain and the EU have au­tho­rized the shot for use, there has been slow up­take around the world as the drug­mak­er and the bloc fought pub­licly over the dos­es the com­pa­ny would pro­vide. And some peo­ple in Eu­ro­pean coun­tries are re­port­ed­ly shun­ning the vac­cine in fa­vor of mR­NA-based shots with high­er topline ef­fi­ca­cy lev­els. — Max Gel­man

Ger­many al­lows use of As­traZeneca’s vac­cine in se­niors — re­port

Days af­ter Cana­di­an of­fi­cials said As­traZeneca’s Covid-19 vac­cine should not be used on se­niors, Ger­many has re­versed its de­ci­sion to re­strict the jab from those 65 and old­er.

The Ger­man Health Min­istry’s Per­ma­nent Vac­cine Com­mis­sion OK’d the vac­cine for use on se­niors on Thurs­day, and an­nounced it would up­date guid­ance to in­cor­po­rate a new rec­om­men­da­tion that dos­es be spaced 12 weeks apart, BBC re­port­ed. 

Health Min­is­ter Jens Spahn called the de­ci­sion “good news for old­er peo­ple who are wait­ing for an in­jec­tion,” per BBC.

The move was based on new ev­i­dence that As­traZeneca and Ox­ford Uni­ver­si­ty pre­sent­ed last month, which they said proves their vac­cine is more ef­fec­tive when ad­min­is­tered over the course of 12 weeks. The new reg­i­men has al­ready been ap­proved by the UK.

In­ves­ti­ga­tors wrote in a Lancet study:

In our study, vac­cine ef­fi­ca­cy was high­er, af­ter the sec­ond dose, in those with a longer prime-boost in­ter­val, reach­ing 82.4% in those with a dos­ing in­ter­val of 12 weeks or more. Point es­ti­mates of ef­fi­ca­cy were low­er with short­er dos­ing in­ter­vals, though it should be not­ed that there is some un­cer­tain­ty as con­fi­dence in­ter­vals over­lap. High­er bind­ing and neu­tral­is­ing an­ti­body titres were ob­served in sera at the longer prime-boost in­ter­val, sug­gest­ing that, as­sum­ing there is a re­la­tion­ship be­tween the hu­moral im­mune re­sponse and ef­fi­ca­cy, these may be true find­ings and not arte­facts of the da­ta.

Back in Jan­u­ary, an ex­pert pan­el in Ger­many rec­om­mend­ed against giv­ing As­traZeneca’s vac­cine to those over the age of 65, cit­ing “in­suf­fi­cient da­ta avail­able to as­sess the vac­cine ef­fi­ca­cy.”

While a Cana­di­an pan­el of vac­cine ex­perts said ear­li­er this week that vac­cines from Pfiz­er/BioN­Tech and Mod­er­na are pre­ferred for those over 65, France al­so de­cid­ed Mon­day to al­low the vac­cine’s use in se­niors. — Nicole De­Feud­is 

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

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; 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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.