Strike three: Bris­tol-My­ers’ third I/O shot at glioblas­toma miss­es as Op­di­vo flops yet again on key end­point

Glioblas­toma con­tin­ues to de­fy about every­thing thrown at it.

Bris­tol-My­ers Squibb put out word Thurs­day morn­ing that its third Phase III as­sault on brain can­cer us­ing its star PD-1 Op­di­vo failed the first end­point, with no sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival for pa­tients who face grim odds.

Check­Mate-548 ap­pears head­ed for a com­plete col­lapse, though over­all sur­vival is still be­ing stud­ied. Re­searchers had tried to see if the check­point ther­a­py could out­do the stan­dard of care by adding it to the stan­dard — temo­zolo­mide and ra­di­a­tion ther­a­py. 

They al­ready tried — and failed — ear­li­er this year with Check­Mate-498, a Phase III that com­bined Op­di­vo and ra­di­a­tion against temo­zolo­mide. That tri­al failed the mark on OS in May.

Two years ago the com­pa­ny was forced to con­cede de­feat on Check­mate-143, the first use of a PD-1 against glioblas­toma.

Bris­tol-My­ers has had a string of set­backs in the clin­ic with Op­di­vo, though the phar­ma gi­ant still en­joys block­buster rev­enue even as Mer­ck’s Keytru­da con­tin­ues its clin­i­cal blitz that put them on top of the mar­ket.

In this case, though, the Bris­tol-My­ers team joins a long list of fail­ures in fight­ing brain can­cer, which re­mains one of the tough­est tar­gets in on­col­o­gy. Ab­b­Vie had its own bit­ter set­back to re­port in May when their an­ti­body-drug con­ju­gate de­patux­izum­ab mafodotin (or de­patux-m; pre­vi­ous­ly known as ABT-414) al­so failed in im­prov­ing sur­vival times for brain can­cer vic­tims.

Sev­er­al years ago Ab­b­Vie showed up at AS­CO with ABT-414 and Ro­va-T to tout their po­ten­tial. Ro­va-T failed com­plete­ly for the R&D team, forc­ing a com­plete write-off of a drug they bought for $5.8 bil­lion up­front.

Robert Prins UCLA

A com­plete fail­ure here won’t ex­tin­guish all hope that a PD-1 could yet play a role in glioblas­toma. Robert Prins at the UCLA Jon­s­son Com­pre­hen­sive Can­cer Cen­ter re­port­ed ev­i­dence ear­li­er this year from a tiny ex­plorato­ry tri­al that a check­point may help pa­tients when used ahead of surgery. But it’s a long shot.

One of the few re­main­ing Phase III stud­ies for glioblas­toma like­ly to read out soon be­longs to Toca­gen $TO­CA which is mak­ing the dif­fi­cult as­sault with To­ca 511/FC. Re­searchers an­nounced sev­er­al months ago that they would con­tin­ue to the fi­nal read­out, dash­ing any hopes for an ear­ly suc­cess. There isn’t much con­fi­dence in this drug, though, with the stock falling from a high north of $15 last fall to just above $3 a share this morn­ing. The mar­ket cap is hold­ing at a mi­cro-lev­el $72 mil­lion.

These fail­ures won’t en­cour­age oth­ers to make a try.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Alaa Halawa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

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Genen­tech to stop com­mer­cial man­u­fac­tur­ing at Cal­i­for­nia head­quar­ters

Genentech is halting commercial manufacturing at its California headquarters — and laying off several hundred employees.

The move is the result of a decision Genentech made in 2007 to relocate manufacturing operations from its South San Francisco headquarters location to other facilities or move the work to CDMOs, said Andi Goddard, Genentech’s SVP of quality and compliance for pharmaceutical technical operations, in an interview with Endpoints News. Genentech has made changes in capabilities and invested more in technology, so it doesn’t need as many large-scale manufacturing facilities as it did in the past, she said.

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Chat­G­PT with phar­ma da­ta de­buts for med­ical meet­ings, be­gin­ning with AACR

What do you get when you combine ChatGPT generative AI technology with specific pharma and clinical datasets? A time-saving tool that can answer questions about medical conference abstracts and clinical findings in seconds in one new application from ZoomRx called FermaGPT.

ZoomRx is debuting a public version of its generative AI product specifically for medical conferences beginning this week for the upcoming American Association for Cancer Research (AACR) annual meeting that runs April 14-19.

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Vas Narasimhan, Novartis CEO (Gian Ehrenzeller/Keystone via AP)

No­var­tis pulls the plug on UK-based car­dio­vas­cu­lar study

Novartis is calling off a UK-based trial for Leqvio in the primary prevention of cardiovascular events in patients with high cholesterol, the company confirmed on Wednesday.

The Swiss pharma giant made the decision after “careful evaluation,” a spokesperson told Endpoints News via email. The trial, dubbed ORION-17, was planned in partnership with England’s National Health Service (NHS) and was part of the company’s strategy to establish Leqvio as a standard of care in cardiovascular disease management.

FDA re­jects Ab­b­Vie's in­fu­sion ther­a­py for Parkin­son's, re­quests more in­fo on pump de­vice

The FDA rejected AbbVie’s 24-hour infusion therapy for Parkinson’s, saying it needs more information on a device used to administer the treatment before it can clear it.

The Chicago-area drugmaker said in a press release that the complete response letter from the agency didn’t include any requests for more efficacy or safety trials related to the drug, known as ABBV-951. The company said it aims to “resubmit the NDA as soon as possible.”

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Quince Ther­a­peu­tics faces takeover bid from share­hold­er Echo Lake Cap­i­tal

A bid to take over the biotech Quince Therapeutics has been put forward by one of its shareholders.

On Tuesday, Echo Lake Capital sent a letter to Quince’s board of directors putting forth a proposal to acquire all the biotech’s stock for $1.60 per share, which would value a takeover at around $58 million.

In the letter, Echo Lake said that it believes Quince’s stock is severely undervalued and that no drugs are being actively marketed or developed that require cash expenditures. It’s trading below the value of its assets, Echo Lake said.

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Rohan Palekar, 89bio CEO

89bio’s PhII da­ta add to quick suc­ces­sion of NASH read­outs as field seeks turn­around

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.