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.”

RE­COV­ERY tri­al up­date:

Colchicine arm stopped for lack of ef­fi­ca­cy in pa­tients hos­pi­talised with COVID-19.https://t.co/hcn9PytegJ pic.twit­ter.com/q09ed­dYXYL

— Mar­tin Lan­dray (@Mar­tin­Lan­dray) March 5, 2021

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.

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.

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.

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 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.

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.