What's killing pa­tients in Bay­er's Xofi­go com­bo study? Re­searchers un­blind study ear­ly to probe safe­ty alert

Back in the spring of 2016, re­searchers re­port­ed that a com­bi­na­tion of Bay­er’s Xofi­go (ra­di­um-223) with Zyti­ga (abi­raterone) came through with ev­i­dence of sig­nif­i­cant­ly re­duced bone pain for men suf­fer­ing from prostate can­cer. But sci­en­tists were forced to un­blind the Phase III piv­otal tri­al pre­ma­ture­ly af­ter an in­de­pen­dent mon­i­tor­ing group spot­ted a high­er rate of deaths in the treat­ment arm.

Mike De­voy

The com­pa­ny, which has been pur­su­ing new can­cer drugs as a core ap­proach to pipeline con­struc­tion, had en­rolled 806 pa­tients who ei­ther got the com­bo or just Zyti­ga, a well es­tab­lished block­buster that helped change the stan­dard of care in prostate can­cer.

Now they’ll be­gin the work need­ed to see why adding Xofi­go — which us­es tar­get­ed al­pha ra­di­a­tion to kill can­cer cells — would al­so trig­ger more deaths and frac­tures. This com­bi­na­tion has been a key part of Bay­er’s strat­e­gy to ex­pand its mar­ket for Xofi­go, which hit the mar­ket with bull­ish peak sales es­ti­mates of $1.5 bil­lion.

The com­bo study is be­ing done at a time thou­sands of new match-up stud­ies are be­ing pur­sued, work­ing un­der the rea­son­able as­sump­tion that com­bin­ing can­cer drugs may well of­fer a longer and bet­ter life for can­cer pa­tients. But they’re not al­ways safe, as the re­cent is­sues with a slate of com­bi­na­tions match­ing Cel­gene’s mul­ti­ple myelo­ma drugs with check­point ther­a­pies un­der­scores — a com­bo sus­pend­ed af­ter in­ves­ti­ga­tors tracked a high­er death rate in the treat­ment arm.

“Pa­tient safe­ty is our top pri­or­i­ty. We are there­fore un­blind­ing the study to thor­ough­ly an­a­lyze the da­ta”, said Mike De­voy, the chief med­ical of­fi­cer at Bay­er. “It is im­por­tant to note that, based on avail­able da­ta from pre­vi­ous tri­als as well as re­al-world use, the ben­e­fit-risk pro­file of Xofi­go in its ap­proved in­di­ca­tion re­mains fa­vor­able. We re­main com­mit­ted to fur­ther ex­plor­ing the po­ten­tial of ra­di­um-223 across mul­ti­ple tu­mor types with sig­nif­i­cant un­met med­ical need, in­clud­ing prostate can­cer.”

Im­age: Shut­ter­stock

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.

The key dates for KRAS watch­ers through the end of the year — the trail is nar­row and risks are ex­treme

There’s nothing quite like a big patent win when it comes to burnishing your prospects in the pipeline. And for Amgen, which seems to have rescued Enbrel for a run to 2029, the cheering section on Wall Street is now fixed on AMG 510 and a key rival.

And it didn’t take much data to do it. 

There was the first snapshot of a handful of patients, with a 50% response rate. Then came word that Amgen researchers are also tracking responses in different cancers, at least one in colorectal cancer and appendiceal too. 

Bain's Or­ly Mis­han joins Pfiz­er's neu­ro spin­out Cerev­el; On­colyt­ic virus biotech taps Sil­la­Jen ex­ec He­le­na Chaye as CEO

→ Bain Capital is deploying one of its top investors to Cerevel Therapeutics, steering a $350 million-plus neuro play carved out of Pfizer. Orly Mishan — a co-founder and principal of Bain’s life sciences unit — was involved in the partnership that birthed the biotech spinout in the first place. As Cerevel’s first chief business officer, she is tasked with corporate development, program management as well as technical operations. 

UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.