Roche's big PhI­II Tecen­triq/Cotel­lic com­bo study for colon can­cer fails, dam­ag­ing Ex­elix­is shares

The Tecen­triq team at Roche/Genen­tech has run in­to an­oth­er nasty set­back. Their PD-L1 drug, com­bined with Cotel­lic, failed to make a sig­nif­i­cant dif­fer­ence on over­all sur­vival among col­orec­tal can­cer pa­tients in the Phase III study. And the fail­ure will have the biggest im­pact on Roche’s part­ner Ex­elix­is, which had a lot rid­ing on the IM­blaze370 tri­al.

The key les­son for in­ves­ti­ga­tors: The vast ma­jor­i­ty of the pa­tients in the study had mi­crosatel­lite sta­ble tu­mors, and they’re flag­ging the out­come here as fresh ev­i­dence that check­points in gen­er­al won’t have much chance of suc­cess. They had been bank­ing on ear­ly tri­al re­sults in­di­cat­ing that adding a MEK in­hibitor — Cotel­lic — could make a big dif­fer­ence. But that the­o­ry has gone down in flames.

Michael Mor­ris­sey

A num­ber of an­a­lysts had ear­li­er giv­en this study — which used re­go­rafenib (Sti­var­ga) for the con­trol arm — a good shot at suc­cess. There were no da­ta in the re­lease, which will like­ly be re­leased at a lat­er con­fer­ence.

Ex­elix­is’ shares had dropped by about 13% on af­ter­noon trad­ing.

The Phase III fail­ure comes a month af­ter the de­vel­op­ment part­ners were forced to halt en­roll­ment of pa­tients in the Phase II MOD­UL study af­ter mon­i­tors tracked a string of deaths in a co­hort of pa­tients in the tri­al. One of those deaths was trig­gered by car­dio­genic shock, which was linked to the com­bo.

Tecen­triq has stum­bled bad­ly be­fore in clin­i­cal tri­als. But as the third big PD-1/L1 to hit the mar­ket, it’s al­so had some no­table suc­cess­es. Most re­cent­ly the FDA of­fered a quick de­ci­sion on a triple com­bo us­ing Tecen­triq with Avastin and chemo for front­line lung can­cer, where Mer­ck has dom­i­nat­ed with Keytru­da as Bris­tol-My­ers scram­bled to be com­pet­i­tive.

In Q1 Mer­ck hit $1.46 bil­lion in Keytru­da rev­enue, up 151% as the phar­ma gi­ant con­tin­ued to out­pace Bris­tol-My­ers on lung can­cer. Bris­tol-My­ers’ Op­di­vo, which got out to an ear­ly lead, scored $1.51 bil­lion, leav­ing them vul­ner­a­ble to drop­ping back to the num­ber two spot. Roche, mean­while, re­port­ed Q1 rev­enue of on­ly $139 mil­lion for Tecen­triq.

Roche, of course, will move along with 50 oth­er stud­ies for Tecen­triq, but Ex­elix­is will be forced to work through the sting­ing fail­ure with sig­nif­i­cant­ly less to of­fer in­vestors in terms of fresh cat­a­lysts to look to.

“We will con­tin­ue to work with Genen­tech on the eval­u­a­tion of co­bime­tinib’s po­ten­tial in oth­er tu­mor types, in­clud­ing in melanoma, in which there are two on­go­ing phase 3 piv­otal tri­als,” said Ex­elix­is CEO Michael Mor­ris­sey in a state­ment. “Sep­a­rate­ly, Ex­elix­is re­mains fo­cused on and com­mit­ted to max­i­miz­ing the po­ten­tial of the cabozan­ti­nib fran­chise through our com­mer­cial ac­tiv­i­ties and on­go­ing clin­i­cal de­vel­op­ment pro­gram eval­u­at­ing the com­pound alone, or in com­bi­na­tion with im­mune check­point in­hibitors, across nu­mer­ous tu­mor types.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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Terrie Curran, Phathom CEO (Credit: Arcutis)

Phath­om's old Take­da drug bests Pre­vacid in a PhI­II GI tri­al. Next stop? The FDA

There’s no time for rest in biopharma — at least not at Phathom Pharmaceuticals. Just over a month after submitting two NDAs for its lead acid-fighter vonoprazan, the biotech is already lining up a third, and collecting an extra $50 million to push things along.

Vonoprazan met its primary non-inferiority endpoints in a Phase III study comparing it to standard-of-care Prevacid in a type of gastroesophageal reflux disease (GERD) called erosive esophagitis (EE). It also proved superior to the popular heartburn drug by multiple measures, including healing rate and maintenance of healing.

Thomas Lingelbach, Valneva CEO

Small biotech says its Covid-19 vac­cine spurs more an­ti­bod­ies than As­traZeneca’s. Will sup­ply deals come now?

In a first, a small runner-up vaccine developer says its own Covid-19 jab has induced “superior neutralizing antibody titer levels” over AstraZeneca’s AZD1222 when pitted head-to-head in a Phase III trial.

That and non-inferiority in seroconversion rate were the co-primary endpoints of the trial, which recruited 4,012 adult volunteers across the UK.

But on the exploratory endpoint of Covid-19 case counts, Valneva notes that both treatment groups saw a similar number of infections.