Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizum­ab. Eye­ing a hy­per-com­pet­i­tive IBD and Crohn’s mar­ket where they have not his­tor­i­cal­ly been a play­er, the com­pa­ny rolled out 8 dif­fer­ent Phase III tri­als, test­ing the an­ti­body for two dif­fer­ent us­es across a range of dif­fer­ent pa­tient groups.

On Mon­day, Roche re­leased re­sults for 4 of those stud­ies, and they mark a de­cid­ed set­back for both the Swiss phar­ma and their biotech sub Genen­tech, po­ten­tial­ly spelling an end to a drug they put over half-a-decade and mil­lions of dol­lars be­hind.

The four stud­ies ex­am­ined etrolizum­ab as a treat­ment for ul­cer­a­tive col­i­tis, test­ing to see if it worked as an in­duc­tion treat­ment for pa­tients who had nev­er had an­ti-TNF ther­a­py (i.e. the mega-block­buster Hu­mi­ra); if it worked as a main­te­nance ther­a­py for peo­ple who had nev­er tak­en an­ti-TNF drugs; and if it worked as both an in­duc­tion and a main­te­nance ther­a­py for pa­tients who had pre­vi­ous­ly tak­en an­ti-TNF drugs.

In one 358-per­son tri­al of pa­tients who had nev­er tak­en an­ti-TNF drugs, etrolizum­ab was bet­ter than place­bo at in­duc­ing re­mis­sion. But in the sec­ond 358-per­son tri­al test­ing the same thing, it wasn’t. In the study that test­ed etrolizum­ab as a main­te­nance ther­a­py, the ex­per­i­men­tal drug proved no bet­ter than place­bo. And in the study that test­ed etrolizum­ab as a main­te­nance and in­duc­tion ther­a­py, etrolizum­ab was bet­ter than place­bo at in­duc­ing re­mis­sion but no bet­ter at sus­tain­ing re­mis­sion.

The re­sult was a hodge­podge of sta­tis­tics that ex­ec­u­tives could on­ly de­scribe as dis­ap­point­ing.

Levi Gar­raway

“We are dis­ap­point­ed with these re­sults, be­cause we know that peo­ple with ul­cer­a­tive col­i­tis need new treat­ment op­tions,” CMO Levi Gar­raway said in a state­ment.

Genen­tech did not re­lease the topline da­ta, but said they will do so at fu­ture med­ical con­fer­ences. The safe­ty re­sults were con­sis­tent with pre­vi­ous stud­ies, the com­pa­ny said.

The re­sults won’t end the late-stage IBD pro­gram, even as it sets it back con­sid­er­ably. In ad­di­tion to open-la­bel ex­pan­sion stud­ies, the com­pa­ny is still run­ning a pair of Phase III tri­als in Crohn’s dis­ease.

Be­hind etrolizum­ab, Genen­tech has one oth­er mid-stage as­set for in­flam­ma­to­ry dis­eases: An IL-22 fu­sion pro­tein now in Phase II for IBD. By con­trast, etrolizum­ab works as an in­te­grin in­hibitor sim­i­lar to Take­da’s En­tyvio.

The mixed bag is the sec­ond set­back for Genen­tech in the past week, af­ter the com­pa­ny’s check­point in­hibitor Tecen­triq failed in a triple-neg­a­tive breast can­cer study on Fri­day.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seattle Genetics have another approval on its hands?

The last 12 months, not so great for the world, has been great for Seattle Genetics. The company landed two separate FDA approvals, signed a $4.5 billion deal with Merck and watched antibody-drug conjugates — the technology they spent years developing to broad industry skepticism — emerge suddenly as one of the most popular approaches in oncology. And on Monday at ESMO, the company and their partners at Genmab unveiled the data behind the ADC it hopes will provide its next major FDA approval.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

Eli Lilly CSO Dan Skovronsky (file photo)

UP­DAT­ED: #ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,400+ biopharma pros reading Endpoints daily — and it's free.

Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,400+ biopharma pros reading Endpoints daily — and it's free.

#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.