Af­ter get­ting skunked by ri­vals, Pfiz­er touts ‘break­through’ can­cer drug lor­la­tinib, heads to the FDA

Mace Rothen­berg, Pfiz­er

Pfiz­er’s Xalko­ri has be­come a Phase III punch­ing bag of sorts for top ri­vals in the can­cer field. In June No­var­tis’ Zyka­dia picked up an FDA ap­proval to chal­lenge Xalko­ri in front­line ALK-pos­i­tive lung can­cer. And Roche’s Ale­cen­sa has been whup­ping up on Xalko­ri as well, prov­ing bet­ter at cut­ting the risk of dis­ease pro­gres­sion.

So it’s no won­der that Pfiz­er is tak­ing its pos­i­tive Phase II da­ta — post­ed to­day — for its next-gen suc­ces­sor lor­la­tinib straight to reg­u­la­tors.

Now in Phase III, Pfiz­er won a break­through ther­a­py des­ig­na­tion for lor­la­tinib from the FDA ear­li­er this year, promis­ing a speedy re­view at an agency that has be­come a mas­ter at mak­ing ac­cel­er­at­ed can­cer drug de­ci­sions.

De­signed for ALK-pos­i­tive and ROS1-pos­i­tive ad­vanced non-small cell lung can­cer, re­searchers high­light­ed a slate of the mid-stage da­ta on the drug.

The key da­ta points:

  • In ALK-pos­i­tive treat­ment-naïve pa­tients, the over­all re­sponse rate was 90%. The in­tracra­nial ORR (IC-ORR) was 75%.
  • For ALK-pos­i­tive pa­tients pre­vi­ous­ly treat­ed with Xalko­ri (crizo­tinib) with or with­out chemother­a­py: ORR was 69%, the IC-ORR was 68%.
  • In ALK-pos­i­tive pa­tients pre­vi­ous­ly treat­ed with a non-crizo­tinib ALK in­hibitor with or with­out chemother­a­py: ORR was 33%.
  • ALK-pos­i­tive pre­vi­ous­ly treat­ed with two or three pri­or ALK in­hibitors with or with­out chemother­a­py: ORR was 39%.
  • ROS1-pos­i­tive re­gard­less of pri­or treat­ment: ORR was 36%.

Now look for Pfiz­er to press hard to punch back at No­var­tis and Roche in de­fense of its can­cer drug fran­chise. Pfiz­er’s made on­col­o­gy a chief fo­cus in the pipeline, scor­ing some of its biggest gains in the field as it added new drugs through the Medi­va­tion buy­out. And as bil­lions gets poured in­to new re­search, pa­tients have ben­e­fit­ed from the quick adop­tion of some game-chang­ing ther­a­pies.

“Lor­la­tinib is an ex­tra­or­di­nary ex­am­ple of what can be achieved through trans­la­tion­al re­search and pre­ci­sion med­i­cine de­vel­op­ment. Re­call that Xalko­ri (crizo­tinib) was the first drug ap­proved for pa­tients with ALK-pos­i­tive and ROS1-pos­i­tive NSCLC. By un­der­stand­ing the mu­ta­tions that oc­curred in pa­tients that ren­dered their tu­mors re­sis­tant to Xalko­ri and oth­er ALK in­hibitors, med­i­c­i­nal chemists work­ing at Pfiz­er were able to de­sign a mol­e­cule with the po­ten­tial to over­come that re­sis­tance and in­hib­it ALK de­spite these mu­ta­tions. We are very en­cour­aged by the re­sults of this Phase 2 tri­al that pro­vide the first clin­i­cal ev­i­dence of the ac­tiv­i­ty of lor­la­tinib in this set­ting,” said Mace Rothen­berg, chief de­vel­op­ment of­fi­cer, on­col­o­gy, Pfiz­er glob­al prod­uct de­vel­op­ment.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; 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.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.