Trad­ing places with Bris­tol-My­ers, Mer­ck hit with an­oth­er late-stage set­back on check­point star Keytru­da

Close to a year af­ter Mer­ck $MRK won an ac­cel­er­at­ed FDA OK to use its PD-1 check­point star Keytru­da for treat­ing sec­ond-line cas­es head and neck squa­mous cell car­ci­no­ma in com­bi­na­tion with plat­inum-con­tain­ing chemo, the phar­ma gi­ant an­nounced that its big Phase III study for that in­di­ca­tion failed.

The piv­otal KEYNOTE-040 tri­al failed to meet the pri­ma­ry end­point on over­all sur­vival in com­par­ing the block­buster check­point against stan­dard ther­a­pies, the phar­ma gi­ant re­port­ed. But the cur­rent ap­proval stands nev­er­the­less, Mer­ck said in a state­ment.

“The com­pa­ny not­ed that the FDA re­mains com­fort­able with the drug’s cur­rent ac­cel­er­at­ed ap­proval in this in­di­ca­tion de­spite the tri­al re­sults,” ob­served Leerink’s Sea­mus Fer­nan­dez. “Im­por­tant­ly, Keytru­da ap­pears to have an­oth­er shot on goal for full ap­proval in H&N can­cer, as the Keynote-048 study in first-line pa­tients could, if pos­i­tive, serve as the con­fir­ma­to­ry tri­al.”

Roger Perl­mut­ter, Mer­ck

Mer­ck didn’t pro­vide a lot of de­tails, but this is the lat­est in a se­ries of set­backs in the field that have be­gun to show the out­er lim­its of ef­fi­ca­cy for a new class of can­cer med that has trans­formed on­col­o­gy ther­a­py in the past two years. But right now, those out­er lim­its of ef­fi­ca­cy run along a blur­ry line, with no clear ex­pla­na­tions for what is caus­ing these sud­den break­downs.

Mer­ck re­cent­ly was forced to put a slate of 3 Keytru­da tri­als for mul­ti­ple myelo­ma on hold af­ter in­ves­ti­ga­tors spot­ted a high­er rate of death in the check­point arm. Two of those stud­ies used com­bi­na­tions with Cel­gene drugs, Po­m­a­lyst and its big drug Revlim­id.

Mer­ck has ini­ti­at­ed hun­dreds of stud­ies, in­clud­ing some 300 com­bi­na­tion stud­ies, as it races to cap­i­tal­ize on its new lead in the field af­ter Bris­tol-My­ers Squibb ran in­to se­ri­ous is­sues with a failed study for lung can­cer. It’s clear that af­ter see­ing some re­mark­able im­prove­ments for a sig­nif­i­cant mi­nor­i­ty of check­point pa­tients, these ther­a­pies have their lim­its. Roche has al­so had its own prob­lems with the fail­ure of a Phase III con­fir­ma­to­ry study us­ing Tecen­triq.

Bris­tol-My­ers’ Op­di­vo, mean­while, post­ed pos­i­tive Phase III da­ta on squa­mous cell car­ci­no­ma of the head and neck back in late 2016, with a me­di­an OS of 7.5 months for Op­di­vo com­pared to 5.1 months for in­ves­ti­ga­tor’s choice.

What to make of that?

“Up un­til yes­ter­day,” not­ed Ever­core ISI’s Umer Raf­fat, “I would have told you that there are at least 2 dif­fer­ent in­di­ca­tions where MRK worked and oth­ers failed … and per­haps MRK is just ex­e­cut­ing these tri­als much bet­ter.  How­ev­er, as of to­day, there ap­pears to be no con­sis­ten­cy in the in­con­sis­ten­cy.  Now MRK failed where BMY worked.”

“We are en­cour­aged by the pos­i­tive im­pact that KEYTRU­DA has had on many can­cer pa­tients, in­clud­ing those with pre­vi­ous­ly treat­ed re­cur­rent or metasta­t­ic head and neck can­cer, and we re­main con­fi­dent that KEYTRU­DA is an im­por­tant ther­a­py for this dif­fi­cult-to-treat can­cer,” said Roger Dansey, late-stage on­col­o­gy de­vel­op­ment leader, Mer­ck Re­search Lab­o­ra­to­ries. “We look for­ward to shar­ing the com­pre­hen­sive da­ta analy­sis from KEYNOTE-040 with the sci­en­tif­ic com­mu­ni­ty at an up­com­ing med­ical meet­ing.”

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.

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.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

Endpoints News

Basic subscription required

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

CEO Pascal Soriot via Getty Images

As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

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.