Bris­tol-My­ers craters af­ter block­buster check­point drug Op­di­vo fails key lung can­cer study

Bris­tol-My­ers Squibb an­nounced this morn­ing that Op­di­vo has flopped in a late-stage study on non-small cell lung can­cer, pre­sent­ing a stun­ning set­back for the star ther­a­py. Its shares $BMY im­me­di­ate­ly plunged 18%, wip­ing out bil­lions in mar­ket val­ue, while ri­val Mer­ck $MRK—a run­ner-up in the check­point mar­ket—saw its shares soar 10%.

Re­searchers had re­cruit­ed a broad pop­u­la­tion of 541 pre­vi­ous­ly un­treat­ed first line pa­tients whose tu­mors ex­pressed PD-L1 at ≥ 5%, a key bio­mark­er used to iden­ti­fy pa­tients most like­ly to re­spond. The Op­di­vo arm was com­pared to a group who re­ceived their physi­cian’s choice of al­ter­na­tive ther­a­pies. But this time, in the first ma­jor re­ver­sal for Bris­tol-My­ers, the drug failed to de­liv­er a sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival.

The fo­cus now may cen­ter on the lev­el of PD-L1 ex­pres­sion used to qual­i­fy pa­tients. Last fall, when the FDA ex­pand­ed its ap­proval of Op­di­vo to NSCLC pa­tients whose can­cer had spread af­ter chemo, FDA can­cer czar Richard Paz­dur not­ed:

“While Op­di­vo showed an over­all sur­vival ben­e­fit in cer­tain non-small cell lung can­cer pa­tients, it ap­pears that high­er ex­pres­sion of PD-L1 in a pa­tient’s tu­mor pre­dicts those most like­ly to ben­e­fit.”

“The missed re­sult like­ly re­flects the fact that BMY pushed the en­ve­lope too far in de­sign­ing its tri­al,” not­ed Bern­stein’s Tim An­der­son. “Specif­i­cal­ly, as men­tioned in the press re­lease to­day, they chose a “cut-off val­ue” for PDL1 ex­pres­sion of 5%.  This is in-line with what we had been say­ing (that 5% was the val­ue), where­as the con­sen­sus view had been that the cut-off was 10%.  By mak­ing it 5%, BMY was in essence try­ing to broad­en the pa­tient pop­u­la­tion where it could claim a ben­e­fit (had re­sults been pos­i­tive, of course), but failed re­sults sug­gest they like­ly made it too broad, mean­ing they en­rolled pa­tients with too lit­tle PDL1 ex­pres­sion, and this soured the over­all analy­sis.  The pop­u­la­tion MRK stud­ied was nar­row­er.”

I/O in­vest­ment spe­cial­ist Brad Lon­car had this to say:

Bris­tol’s more ag­gres­sive strat­e­gy of fo­cus­ing on a broad­er pop­u­la­tion rather than high PD-L1 ex­pres­sors has worked out for them in lat­er stages of dis­ease, but it looks like that has fi­nal­ly reached its lim­it. This is a very dis­ap­point­ing re­sult, but I think they de­serve cred­it for try­ing to help as many pa­tients as pos­si­ble.

Mer­ck has been lag­ging far be­hind Bris­tol-My­ers Squibb in the check­point sales race, with

Gio­van­ni Caforio, Bris­tol-My­ers Squibb CEO

Op­di­vo OK’d for use with­out a di­ag­nos­tic test while Keytru­da pa­tients have to be screened. Free of test­ing pa­tients, Op­di­vo has raced far ahead on the sales front. But Keytru­da—which was test­ed in pa­tients with a PD-L1 ex­pres­sion of 50%—looks to have the edge now in a key mar­ket­place.

These two pi­o­neer­ing drugs work es­sen­tial­ly the same way. They both dis­man­tle a hur­dle that can­cer cells re­ly on to es­cape an at­tack by the im­mune sys­tem. That has proven to be a game-chang­er in many types of can­cer, where new com­bi­na­tions are now be­ing test­ed to pro­vide a one-two punch against can­cer cells.

Gio­van­ni Caforio, the CEO at Bris­tol, had this to say:

While we are dis­ap­point­ed Check­Mate -026 did not meet its pri­ma­ry end­point in this broad pa­tient pop­u­la­tion, we re­main com­mit­ted to im­prov­ing pa­tient out­comes through our com­pre­hen­sive de­vel­op­ment pro­gram, in­clud­ing the on­go­ing Phase 3 Check­Mate -227 study ex­plor­ing the po­ten­tial of the com­bi­na­tion of Op­di­vo plusYer­voy for PD-L1 pos­i­tive pa­tients, and Op­di­vo plus Yer­voy, or Op­di­vo plus chemother­a­py in PD-L1 neg­a­tive pa­tients.


via Brad Lon­car
Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.


ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology


ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development


CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

UP­DAT­ED: As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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SEC calls out lit­tle Ther­a­peu­tic­sMD for its in­sid­er con­tacts with an­a­lysts to boost share price, then halt rout

Back in May 2017, following an FDA rejection, TherapeuticsMD saw its share price plummet to the lowest levels in two years. The little Florida biotech eventually found its way back to the good side of regulators, scoring a curious OK a year later for its therapy preventing vaginal pain during sex. But the SEC is now accusing it of selectively disclosing nonpublic information in attempts to manipulate its stock.

In two instances in June and July of 2017, TherapeuticsMD allegedly violated the Regulation Fair Disclosure rule by sharing material information with certain sell-side analysts and not the public, resulting in a more favorable stock move than otherwise would be expected.

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Therapists Marcela Ot'alora and Bruce Poulter are trained to conduct MDMA-assisted psychotherapy. In this reenactment, they demonstrate how they help guide and watch over a patient who is revisiting traumatic memories while under the influence of MDMA. (Photo: Multidisciplinary Association for Psychedelic Studies)

MD­MA, now in Phase III, shows promise as a PTSD treat­ment

The first time Lori Tipton tried MDMA, she was skeptical it would make a difference.

“I really was, at the beginning, very nervous,” Tipton said.

MDMA is the main ingredient in the club drug known as ecstasy or molly. But Tipton wasn’t taking pills sold on the street to get high. She was trying to treat her post-traumatic stress disorder by participating in a clinical trial.

After taking a dose of pure MDMA, Tipton lay in a quiet room with two specially trained psychotherapists. They sat next to her as she recalled some of her deepest traumas, such as discovering her mother’s body after Tipton’s mother killed two people and then herself in a murder-suicide.

Ted Ashburn. Oncorus

Cowen, Per­cep­tive lead $79.5M Se­ries B for 's­tand­out' biotech shep­herd­ing on­colyt­ic virus to clin­ic

As several Big Pharma players secure biotech partners in the oncolytic virus space for new immuno-oncology combos, Cowen and Perceptive Advisors have come out with their own bet on a startup that promises to shine.

The marquee investors are joining MPM, Deerfield, Celgene, Astellas, Arkin Bio Ventures and UBS Oncology Impact Fund in backing the drug developer, Oncorus, which will now deploy the $79.5 million in Series B cash toward clinical development of its lead program. Other new investors include Surveyor Capital, Sphera Funds, IMM Investment, QUAD Investment Management, UTC Investment, SV Investment Corp and Shinhan Investment-Private Equity, the last five of which are Korean-based funds.

Fu­til­i­ty analy­sis au­gurs de­feat in piv­otal tri­al test­ing of Nu­Cana's lead drug in metasta­t­ic pan­cre­at­ic can­cer

Nearly two years after making its public debut, UK-based NuCana’s mission to make chemotherapies more potent and safer was dealt a blow, after a pivotal study testing its lead experimental drug halted enrollment in a hard-to-treat advanced form of cancer, following a futility analysis.

The drug, Acelarin, is being evaluated for use in metastatic pancreatic cancer patients who were not considered suitable for combination chemotherapy. In the late-stage ACELARATE study — which compared the experimental drug against the chemotherapy gemcitabine — 200 patients had been enrolled by the sponsor, Clatterbridge Cancer Centre, before an analysis from an independent safety and data monitoring panel suggested the study’s main goal would not be met.