Skep­tics pounce af­ter Bris­tol-My­ers scores an ear­ly hit on Op­di­vo-Yer­voy com­bo for lung can­cer

Bris­tol-My­ers Squibb’s close­ly watched study dubbed Check­mate-227 hit ear­ly, with re­searchers tout­ing a suc­cess for their com­bi­na­tion of Op­di­vo and Yer­voy in treat­ing front­line non-small cell lung can­cer cas­es.

Gio­van­ni Caforio

In a state­ment the com­pa­ny $BMY says that re­searchers tracked a “high­ly” sig­nif­i­cant pro­gres­sion-free sur­vival rate for pa­tients with a high tu­mor mu­ta­tion bur­den (TMB), re­gard­less of PD-L1 ex­pres­sion. Their com­bi­na­tion was com­pared with chemo in the study, which is still track­ing for over­all sur­vival re­sults.

That’s a sig­nif­i­cant group, an­a­lysts note, point­ing to Bris­tol-My­ers’ pro­jec­tion that the TMB crowd ac­counts for 45% of all front­line pa­tients. Bris­tol-My­ers re­designed the study to go af­ter the bio­mark­er af­ter stum­bling on a piv­otal tri­al that in­volved a pa­tient pop­u­la­tion that was not so nar­row­ly de­fined. All the de­vel­op­ers are shift­ing to a bio­mark­er fo­cus as they duke it out for spe­cif­ic slices of a mega block­buster-sized mar­ket.

Skep­tics, though, be­gan to re­tal­i­ate ear­ly, and af­ter a sharp jump ear­ly in the day, shares are trad­ing down 3% as crit­ics won­der if Bris­tol-My­ers can fol­low through with con­vinc­ing da­ta. We asked lung can­cer ex­pert Jack West for his take, which you can see here, ques­tion­ing the way the bio­mark­er was han­dled and not­ing that prac­ti­tion­ers will need to see more be­fore chang­ing the way they treat pa­tients.

Hus­tling along in search of pos­i­tive da­ta, Bris­tol-My­ers es­sen­tial­ly in­te­grat­ed two par­al­lel stud­ies in­volv­ing more than 1,700 pa­tients. And R&D chief Tom Lynch told an­a­lysts this morn­ing that there’s more work to be done on TMB-de­fined stud­ies, with up­com­ing da­ta read­outs on gas­tric, lung and head and neck can­cers.

Some an­a­lysts had been won­der­ing if Bris­tol-My­ers might just call a suc­cess to­day, with its Q4 re­port com­ing up. Past mishaps for  Op­di­vo in the all-im­por­tant NSCLC group cost it big time as Mer­ck surged ahead with a com­bi­na­tion of Keytru­da and chemo.

Just a few days ago Sea­mus Fer­nan­dez at Leerink not­ed:

While suc­cess at the OS in­ter­im rep­re­sents a very high bar, this would be a huge­ly pos­i­tive sur­prise. We be­lieve a win here would sug­gest that Op­di­vo + Yer­voy could have a crit­i­cal­ly im­por­tant place in the treat­ment of NSCLC.

Bris­tol-My­ers CEO Gio­van­ni Caforio called it a “break­through in can­cer re­search and a mean­ing­ful step for­ward in de­ter­min­ing which first-line lung can­cer pa­tients may ben­e­fit most from the com­bi­na­tion of Op­di­vo and Yer­voy.”

“TMB has emerged as an im­por­tant bio­mark­er for the ac­tiv­i­ty of im­munother­a­py. For the first time, this Phase 3 study shows su­pe­ri­or PFS with first-line com­bi­na­tion im­munother­a­py in a pre­de­fined pop­u­la­tion of NSCLC pa­tients with high TMB,” said Matthew Hell­mann, study in­ves­ti­ga­tor and med­ical on­col­o­gist at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter. “Check­Mate-227 showed that TMB is an im­por­tant, in­de­pen­dent pre­dic­tive bio­mark­er that can iden­ti­fy a pop­u­la­tion of first-line NSCLC pa­tients who may ben­e­fit from the nivolum­ab plus ip­il­i­mum­ab com­bi­na­tion.”

Not every­one was im­pressed by the top-line re­sults, though.

The win here is al­so a plus for Foun­da­tion Med­i­cine $FMI, which pro­vid­ed the test used to pick pa­tients with a high TMB.

As­traZeneca — which ear­li­er record­ed a ma­jor fail for its com­bi­na­tion of its check­point drug Imfinzi and treme­li­mum­ab, an­oth­er PD-1/L1 check­point com­bined with an ex­per­i­men­tal CT­LA-4 drug — failed the first step on PFS with their com­bo. The OS da­ta is due out lat­er in the year.

The im­pli­ca­tions for Bris­tol-My­ers are con­sid­er­able. An ear­ly leader in the field, the R&D team on Op­di­vo have been work­ing fever­ish­ly to get their PD-1 back on track fol­low­ing a key miss in lung can­cer. But a suc­cess here on PD-1/CT­LA-4 will like­ly trig­ger fresh chat­ter of a pos­si­ble takeover bid by Pfiz­er, which has nev­er lost its ap­petite for a mega-merg­er. On the oth­er hand, such a takeover would al­so threat­en one of the most in­no­v­a­tive of the big bio­phar­ma com­pa­nies.

Op­di­vo earned close to $5 bil­lion last year, a 31% in­crease over 2016, mak­ing this their biggest sell­ing fran­chise drug. Eliquis is now their num­ber two ther­a­py, high­light­ing Op­di­vo’s over­sized role in the com­pa­ny’s fu­ture.

 

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Fireside chat between Hal Barron and John Carroll, UKBIO19

It’s time we talked about bio­phar­ma — live in Lon­don next week

Zoom can only go so far. And I think at this stage, we’ve all tested the limits of staying in touch — virtually. So I’m particularly happy now that we’ve revved up the travel machine to point myself to London for the first time in several years.

Whatever events we have lined up, we’ve always built in plenty of opportunities for all of us to get together and talk. For London, live, I plan to be right out front, meeting with and chatting with the small crowd of biopharma people we are hosting on October 12 at Silicon Valley Bank’s London headquarters. And there’s a lengthy mixer at the end I’m most looking forward to, with several networking openings between sessions.

Take­da to pull key hy­poparathy­roidism drug from the mar­ket af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024, but the entire inventory will be available until depleted or expired, a company spokesperson said via email.

Pfizer and BioNTech's original Marvel comic book links evolving Covid vaccine science to Avengers' evolving villain-fighting tools.(Source: Pfizer LinkedIn post)

Pfiz­er, BioN­Tech part­ner with Mar­vel for Avengers and Covid-fight­ing com­ic book

Pfizer and BioNTech are collaborating with Marvel to celebrate “everyday” people getting Covid-19 vaccines in a custom comic book.

In the “Everyday Heroes” digital comic book, an evolving Ultron, one of the Avengers’ leading villains, is defeated by Captain America, Ironman and others. The plotline and history of Ultron is explained by a grandfather who is waiting with his family at a clinic for Covid-19 vaccinations.

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Kaile Zagger, Infinant Health CEO

UC Davis mi­cro­bio­me spin­out re­brands in­fant sup­ple­ment busi­ness with na­ture fo­cus

When Kaile Zagger took the helm of UC Davis spinout Evolve Biosystems several months ago, the company billed itself as a probiotic maker.

However, she believes the company’s Evivo supplement designed to help infants develop a healthy gut microbiome is “so much more” — and that, she said, calls for a rebrand.

Evolve has, well, evolved into Infinant Health, the company announced on Monday. The new name is a mash-up of the words “infant” and “infinite,” representing the company’s goal of expanding beyond infant care. While its sole product, Evivo, is intended for newborns, Infinant is “quickly developing” an option for kids through the age of two.

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The FDA on Wednesday set Dec. 13 as the day that its Cardiovascular and Renal Drugs Advisory Committee will review Cytokinetics’ potential heart drug, meaning regulators aren’t likely to meet the Nov. 30 PDUFA date that was previously set.

The drug, known as omecamtiv mecarbil, read out its first Phase III in November 2020, hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as the key to breaking into the market, failing to significantly differ in reducing cardiovascular death from placebo.

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Bob Azelby, Eliem Therapeutics CEO

Eliem says ear­li­er drug ex­po­sure is­sues have been re­solved, drops one epilep­sy in­di­ca­tion

After being forced to delay two Phase IIa trials and blaming CMC issues on a Phase Ib miss, Eliem Therapeutics believes it’s now in the clear.

The Seattle and UK-based biotech put out word Wednesday morning about how it conducted new early-stage studies to confirm why low exposure issues arose during the Phase Ib. After researchers compared the results of the studies, Eliem found “no meaningful difference” between them and ruled out CMC as the reason for the foiled Phase Ib study, the company said in a press release.

GSK touts topline win for PD-1 in head-to-head with Keytru­da — while steer­ing next big check­point drug in­to PhI­II

GSK is claiming a win for what it calls the largest head-to-head trial pitting a PD-1 against Merck’s best-selling Keytruda in a type of lung cancer, as its Jemperli met the primary endpoint of objective response rate.

In a separate positive move, GSK says it’s moving both arms of the COSTAR Lung trial into Phase III to test Jemperli as well as the TIM-3 inhibitor cobolimab.

Hesham Abdullah, GSK’s global head of oncology development, said in a statement that the two trials “support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development programme when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options.”

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