Weeks af­ter Keytru­da CRL in high-risk TNBC, Mer­ck claims a win af­ter da­ta ma­ture. How soon will it re­turn to FDA?

There’s been much afoot re­gard­ing Mer­ck’s at­tempts to ex­pand its block­buster Keytru­da drug in­to high-risk, ear­ly-stage triple-neg­a­tive breast can­cer so far in 2021.

In ear­ly Feb­ru­ary, well af­ter Mer­ck had sub­mit­ted its sup­ple­men­tal BLA for the in­di­ca­tion, the FDA’s ODAC unan­i­mous­ly re­buked the phar­ma’s pitch, say­ing the da­ta were too im­ma­ture to be con­clu­sive. FDA can­cer czar Richard Paz­dur took the ex­tra­or­di­nary step of ad­mon­ish­ing Mer­ck dur­ing the meet­ing, say­ing the com­pa­ny should not have as­sumed or hoped for a pos­i­tive re­sult be­fore the piv­otal study read out. A few weeks lat­er, reg­u­la­tors un­sur­pris­ing­ly hand­ed Mer­ck a com­plete re­sponse let­ter.

Now, though, the study has reached the in­ter­im analy­sis check­point. And Mer­ck says it’s a win­ner.

The KEYNOTE-522 study — the same tri­al un­der the mi­cro­scope in Feb­ru­ary’s ad­comm — met its dual pri­ma­ry end­point of event-free sur­vival, Mer­ck an­nounced Thurs­day morn­ing, demon­strat­ing a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in EFS com­pared to the con­trol. Its oth­er pri­ma­ry end­point, patho­log­i­cal com­plete re­sponse, had pre­vi­ous­ly been met.

Roy Baynes

“Now that we are see­ing the da­ta ma­ture af­ter four years to in­clude a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in event-free sur­vival, we look for­ward to work­ing with the FDA and oth­er glob­al au­thor­i­ties,” Roy Baynes, CMO of Mer­ck Re­search Lab­o­ra­to­ries, said in a state­ment.

Mer­ck has been look­ing to ex­pand Keytru­da in­to this TNBC pop­u­la­tion as both a pre-op­er­a­tive (with chemo) and post-op (with­out chemo) treat­ment. The ear­ly da­ta pre­sent­ed at Feb­ru­ary’s ad­comm proved a re­al stick­ing point, with even some pa­tient ad­vo­cates won­der­ing what the rush was all about.

At the time of the last check-in, re­searchers had seen just 53% of tar­get­ed EFS events and 32% of over­all sur­vival events.

It’s not yet clear whether or not the new re­sults will change the agency’s mind re­gard­ing this in­di­ca­tion, giv­en Mer­ck says the EFS da­ta are now good to go. OS is a sec­ondary end­point in this study, and Mer­ck did not dis­close any re­lat­ed in­for­ma­tion in Thurs­day’s an­nounce­ment.

At least one an­a­lyst thinks Thurs­day’s an­nounce­ment will ul­ti­mate­ly set up Mer­ck for a re­bound at the FDA. Bar­clays’ Carter Gould wrote to in­vestors that al­though there were no quan­ti­ta­tive da­ta re­leased, Mer­ck could see a po­ten­tial ap­proval as ear­ly as next year.

“These da­ta should di­rect­ly ad­dress the pan­el’s re­cent con­cern over the lack of ma­ture EFS da­ta, and we would ex­pect Mer­ck to re­file based on these da­ta,” Gould wrote. “This shouldn’t be sur­pris­ing as Mer­ck it­self high­light­ed dur­ing the Ad­Com that the study had 75-95%+ chance of demon­strat­ing a sta­tis­ti­cal­ly sig­nif­i­cant ben­e­fit based on its mod­el­ing as­sump­tions at the time.”

Even though Keytru­da has be­come one of the best-sell­ing drugs on the plan­et, bring­ing in al­most $3.9 bil­lion in this year’s first quar­ter, high-risk TNBC has proven a rare stum­bling block for Mer­ck. Be­fore the ad­comm re­buff, Keytru­da had al­ready come up short to Roche’s ri­val Tecen­triq in pa­tients with PD-L1-ex­press­ing TNBC that have un­re­sectable and lo­cal­ly re­cur­rent or metasta­t­ic tu­mors. Mer­ck even­tu­al­ly gained the thumbs up here last No­vem­ber.

But Tecen­triq pre­vi­ous­ly failed a con­fir­ma­to­ry study for the first-line treat­ment of the PD-L1 group, which may end up putting its ac­cel­er­at­ed ap­proval in jeop­ardy. ODAC vot­ed 7 to 2 in April to main­tain its OK, how­ev­er, as part of the FDA’s broad­er re­view of ac­cel­er­at­ed ap­provals that missed their pri­ma­ry end­points in the con­fir­ma­to­ry fol­low-ups.

So­cial: Va­leriya Zankovych/Shut­ter­stock

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.

His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.