Op­di­vo/Yer­voy com­bo for melanoma fails in key pa­tient pop­u­la­tion

Bris­tol-My­ers Squibb’s ef­forts to ex­pand their check­point in­hibitor com­bi­na­tion have run in­to an­oth­er re­cal­ci­trant can­cer.

The NJ-based phar­ma an­nounced that a com­bi­na­tion of Yer­voy and Op­di­vo didn’t beat out Op­di­vo alone in pa­tients with re­sect­ed high-risk melanoma who had very low lev­els of PD-L1. The drug com­bo couldn’t im­prove re­cur­rence-free sur­vival in these post-surgery pa­tients.

The re­sults mean that adding a CT­LA4 in­hibitor to a PD-1 in­hibitor didn’t help the pa­tients who lacked PD-L1 lig­ands. Bris­tol-My­ers is con­tin­u­ing the study, Check­mate-915,  to see if the com­bo helps the larg­er, all-com­er pool.

Al­though the tri­al will go on, the fail­ure of PD-1 neg­a­tive pa­tients is sig­nif­i­cant, Check­point com­bi­na­tion ther­a­pies were ex­plored in part on the promise of help­ing pa­tients who didn’t test pos­i­tive for PD-L1 — a pop­u­la­tion that rep­re­sents about 60% of melanoma pa­tients, per some es­ti­mates.

The New Eng­land Jour­nal of Med­i­cine study that bur­nished the first FDA ap­proved check­point com­bi­na­tion ther­a­py in 2015 — a com­bi­na­tion of Op­di­vo and Yer­voy in unre­sectable melanoma — showed that com­pared with Op­di­vo alone, the com­bo more than dou­bled pro­gres­sion-free sur­vival in PD-L1 neg­a­tive pa­tients, from 5.3 months to 11.2 months. Sub­se­quent da­ta showed it al­so brought slight im­prove­ments in over­all sur­vival.

Al­though Bris­tol-My­ers had the ear­ly lead on check­point ther­a­pies, they’ve been los­ing out to Mer­ck and their PD-1, Keytru­da — a drug some an­a­lysts ex­pect to top $20 bil­lion by 2024. That race and their lag­ging place helped trig­ger the Cel­gene ac­qui­si­tion that clos­es to­day.

Com­bi­na­tion check­points ther­a­py has been a mixed but most­ly suc­cess­ful strat­e­gy for Bris­tol-My­ers Squibb. Last year, the com­bo failed a Phase III for small cell lung can­cer. Three, though have been ap­proved and the com­pa­ny has pushed hard for more, most re­cent­ly tout­ing the re­sults of a Phase III tri­al on non-small cell lung can­cer and win­ning break­through sta­tus and speedy re­view for liv­er can­cer.

The idea of com­bin­ing these two check­point in­hibitors in­to a sin­gle ther­a­py is to bet­ter tar­get the tu­mor and over­come re­sis­tance by hit­ting it in dif­fer­ent ways. But crit­ics note they have rarely led to huge in­creas­es in sur­vival over sin­gle-agent ther­a­pies and that to­geth­er, the two can lead to high tox­i­c­i­ties.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, just two weeks after submitting a supplemental BLA. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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David Reese, Amgen R&D chief

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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GSK and IQVIA launch plat­form of US vac­ci­na­tion da­ta, show­ing drop in adult rates

Throughout the Covid-19 pandemic, the issue of vaccine uptake has been a point of contention, but a new platform from GSK and IQVIA is hoping to shed more light on vaccine data, via new transparency and general awareness.

The two companies have launched Vaccine Track, a platform intended to be used by public health officials, medical professionals and others to strengthen data transparency and display vaccination trends. According to the companies, the platform is intended to aid in increasing vaccine rates and will provide data on trends to assist public health efforts.

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Ab­b­Vie sur­veys emo­tion­al im­pact of chron­ic leukemia con­di­tion, finds 'roller coast­er' of emo­tions

Rare diseases often have more than just physical effects on patients — especially when it comes to chronic conditions. In the case of the rare slow-growing blood cancer chronic lymphocytic leukemia (CLL), AbbVie wanted to try to assess the mental and emotional toll on patients.

So it surveyed more than 300 CLL patients, caregivers and physicians. While each group differed in how they felt — caregivers overwhelmingly (81%) felt positive about their role, for instance — patients described a “roller coaster” of emotions traversing diagnosis to treatment to remission and even relapse for some.

FDA's vac­cine ad­comm to re­view first fe­cal trans­plant to treat C. dif­fi­cile in­fec­tions

Back in 2018, Swiss drugmaker Ferring Pharmaceuticals made a big bet on Minnesota-based Rebiotix, buying up the company for its experimental poop-based drug implant to treat an infection caused by C. difficile, a potentially dangerous bacteria, in a new way.

Four years later, Ferring’s fecal microbiota transplant, dubbed RBX2660 or Rebyota, will face the FDA’s adcomm of outside vaccine experts on Sept. 22, debating whether the agency should license the transplant as a treatment for adults following antibiotic treatment for recurrent C. difficile infection.