Am­gen hit with a set­back as Kypro­lis fails a key front­line tri­al for mul­ti­ple myelo­ma

Sean Harp­er, Ex­ec­u­tive Vice Pres­i­dent, Re­search and De­vel­op­ment

Am­gen re­port­ed ear­ly Tues­day that Kypro­lis has failed a Phase III tri­al for front­line use against mul­ti­ple myelo­ma, a set­back that can on­ly fur­ther sharp­en the dis­ap­point­ment an­a­lysts have felt for this ther­a­py in light of weak sales.

In­ves­ti­ga­tors say that Kypro­lis com­bined with mel­pha­lan and pred­nisone es­sen­tial­ly matched a triple com­bo us­ing Take­da’s Vel­cade. The PFS for Kypro­lis was 22.3 months com­pared to 22.1 months for the Vel­cade arm.

Am­gen’s shares slid 2.3% in pre-mar­ket trad­ing Tues­day.

The over­all sur­vival da­ta have yet to ma­ture for a read out, ac­cord­ing to Am­gen. But the big biotech didn’t have any­thing pos­i­tive to re­port this morn­ing.

Am­gen had been hop­ing to use this study to help jus­ti­fy the $10.4 bil­lion ac­qui­si­tion of Onyx Phar­ma­ceu­ti­cals back in 2013, af­ter Onyx had pushed the treat­ment through to an ap­proval. Last year, Am­gen had been bull­ish about its prospects in the blood can­cer field af­ter Kypro­lis proved more ef­fec­tive in help­ing mul­ti­ple myelo­ma pa­tients who had failed at least one pri­or treat­ment com­pared to Vel­cade. And it fol­lowed up with a new ap­proval for use against re­lapsed mul­ti­ple myelo­ma in com­bi­na­tion with Vel­cade.

Front­line use, though, would have opened up a ma­jor mar­ket op­por­tu­ni­ty to Am­gen that the com­pa­ny bad­ly need­ed. Kypro­lis earned $512 mil­lion last year, up 55% from the year be­fore. But you’ll find it at the tail end of the drugs Am­gen re­ports on, leav­ing the big biotech look­ing for new ways to add rev­enue. Vel­cade, mean­while, brings in block­buster cash for Take­da, earn­ing more than $2.5 bil­lion a year.

Cel­gene is the leader in mul­ti­ple myelo­ma, though, dom­i­nat­ing the field with Revlim­id and Po­m­a­lyst while J&J and Bris­tol-My­ers Squibb have jumped in with Darza­lex and Em­plic­i­ti.

Look­ing over the field and weigh­ing the set­back at Am­gen, Leerink’s Ge­of­frey Porges con­clud­ed that gener­ic Vel­cade will be the dom­i­nant drug in use. He con­clud­ed:

“With the mul­ti­ple myelo­ma field search­ing for the op­ti­mum com­bi­na­tion treat­ment com­bi­na­tion it seems like­ly that soon-to-be-gener­ic Vel­cade will be the pro­tea­some in­hibitor of choice in front line pa­tients with the back­bone of J&J’s (JNJ, [OP]) Darza­lex (dara­tu­mum­ab)‎, Cel­gene’s (CELG, [MP]) Revlim­id (lenalido­mide), and dex­am­etha­sone (aka Darza­lex/ Rev/ Dex). Vel­cade’s patent is set to ex­pire in 2017. A num­ber of Kypro­lis stud­ies are still on­go­ing – and we are cau­tious about the out­comes. These tri­als in­clude AR­ROW, a phase 3 tri­al of Kypro­lis (with dex) re­lapsed and re­frac­to­ry MM, set to read-out mid- 2017; a phase 3 com­par­ing Kypro­lis vs. Vel­cade (both with rev/ dex) in new­ly di­ag­nosed MM, set to read-out 2H 2017; and the over­all sur­vival da­ta of phase 3 EN­DEAV­OR study of Kypro­lis vs. Vel­cade (both with dex) in re­lapsed MM ex­pect­ed 2018.”

Said R&D chief Sean Harp­er:

“The CLAR­I­ON re­sults, gen­er­at­ed in the con­text of a mel­pha­lan-con­tain­ing reg­i­men, are dis­ap­point­ing, es­pe­cial­ly giv­en the ro­bust da­ta we’ve seen in the sec­ond-line set­ting. How­ev­er, the myelo­ma land­scape has changed dra­mat­i­cal­ly since the de­sign of the CLAR­I­ON study with very few new­ly di­ag­nosed pa­tients treat­ed with mel­pha­lan-based reg­i­mens, par­tic­u­lar­ly in the U.S.  We re­main com­mit­ted to ex­plor­ing Kypro­lis in com­bi­na­tion with oth­er agents to ad­vance the treat­ment of mul­ti­ple myelo­ma.”


What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Mi­rati's KRAS drug looks like the fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed response rates grater than sotorasib solo  and as part of combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.