Hervé Hoppenot, Incyte CEO (Jeff Rumans for Endpoints News)

FDA un­sur­pris­ing­ly brings down the ham­mer on In­cyte's PD-1 — draw­ing a line for fu­ture ac­cel­er­at­ed ap­provals

It ap­pears the PD-(L)1 hon­ey­moon is fi­nal­ly over.

In­cyte $IN­CY re­vealed late Fri­day the FDA has slammed its PD-1 reti­fan­limab — which was un­der pri­or­i­ty re­view for lo­cal­ly ad­vanced or metasta­t­ic squa­mous cell car­ci­no­ma of the anal canal — with a com­plete re­sponse let­ter, de­mand­ing “ad­di­tion­al da­ta” to show clin­i­cal ben­e­fit.

On one hand, the re­jec­tion should come as no sur­prise: Reg­u­la­tors spelled out the prob­lems they saw with In­cyte’s da­ta pack­age in no un­cer­tain terms, rais­ing con­cerns about the low re­sponse rates, lack of di­ver­si­ty and dearth of safe­ty da­ta in the sin­gle-arm tri­al. Dur­ing the en­su­ing ad­comm, the FDA’s can­cer czar, Richard Paz­dur, sug­gest­ed the whole episode un­der­scores the need to “re­assess” how drugs get ap­proved un­der the ac­cel­er­at­ed ap­proval path­way with­out ran­dom­ized stud­ies.

The ex­pert pan­el con­vened to ad­vise on the BLA, echo­ing those con­cerns, vot­ed 13-4 to de­fer an ap­proval un­til more da­ta are avail­able from a place­bo-con­trolled tri­al.

On the oth­er, it sig­nals an of­fi­cial shift in the agency’s han­dling of check­point block­ers, if not can­cer drugs in gen­er­al: Five years af­ter the land­mark first ap­proval for Mer­ck’s Keytru­da, and with eight PD-(L)1 drugs on the mar­ket, there will be no more easy pass­es.

Com­ing on­to an in­creas­ing­ly crowd­ed land­scape in 2017 via a $900 mil­lion deal with Macro­Gen­ics, In­cyte had elect­ed to fol­low a strat­e­gy de­ployed by oth­er late­com­ers like Re­gen­eron. In­stead of go­ing head to head with the dom­i­nant play­ers in ma­jor in­di­ca­tions, the biotech ze­roed in on niche can­cer types with small pa­tient pop­u­la­tions des­per­ate for new ther­a­pies.

Hervé Hop­penot, CEO of In­cyte, held on to that fact in a state­ment.

“Pa­tients with SCAC who have pro­gressed af­ter first-line chemother­a­py cur­rent­ly do not have ap­proved treat­ment op­tions,” he said. “While we are not sur­prised with the FDA de­ci­sion giv­en the ODAC rec­om­men­da­tion, we are dis­ap­point­ed.”

The com­pa­ny will be work­ing with the FDA to “ad­dress feed­back and de­ter­mine next steps,” he added.

A few months ago, In­cyte start­ed en­rolling for a 300-pa­tient Phase III place­bo-con­trolled study with the help of its Chi­nese part­ners at Zai Lab. But da­ta aren’t sched­uled to come out un­til the end of 2024.

In the mean­time, physi­cians are al­so study­ing Mer­ck’s Keytru­da and Bris­tol My­ers Squibb’s Op­di­vo for dif­fer­ent sub­types of anal can­cer.

For Mizuho an­a­lyst Mara Gold­stein, the large­ly ex­pect­ed de­ci­sion isn’t the end of the world for In­cyte.

“Ul­ti­mate­ly, we still view reti­fan­limab as a fa­cil­i­ta­tor of clin­i­cal ac­tiv­i­ty in com­bi­na­tions rather than a growth dri­ver in and of it­self,” she wrote in a note.

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

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Mathai Mammen (Rob Tannenbaum, Endpoints News at BIO 2018)

Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck five years ago, where the soft-spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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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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Andy Jassy, Amazon CEO (Isaac Brekken/AP Images for NFL, File)

Up­dat­ed: FDA slaps Ama­zon with a warn­ing let­ter for sell­ing OTC mole re­moval prod­ucts

The FDA’s Center for Drug Evaluation and Research on Tuesday released a warning letter sent last week to Amazon CEO Andy Jassy in Seattle for selling mole removal products over-the-counter, or, as the FDA explains, “introducing, delivering, or causing the introduction or delivery into interstate commerce of products that are unapproved new drugs.”

“There are no over-the-counter (OTC) drugs that can be legally sold for mole or skin tag removal, and FDA has safety concerns about drugs marketed OTC directly to consumers for these uses,” the agency said in its Aug. 4 warning.

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, less than two weeks after its supplemental BLA was accepted. 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.

Civi­ca, Mayo Clin­ic and oth­ers sound off on FDA draft guid­ance to mit­i­gate drug short­ages

Several pharma groups are laying out the positives and negatives of new FDA draft guidance on how best to handle drug shortages.

The draft is intended to help companies develop and implement risk management plans (RMPs) to assist with any shortages of drugs or biologics. The guidance recommends a framework and factors for stakeholders to develop RMPs for their establishments, API manufacturers and others.

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HHS Secretary Xavier Becerra (Patrick Semansky/AP Images)

US weighs new route of ad­min­is­tra­tion for mon­key­pox vac­cine as cas­es climb — re­port

Less than a week after HHS Secretary Xavier Becerra declared monkeypox a national health emergency, reports have emerged that the US plans to extend its vaccine supply by opting for a different route of administration.

Officials are expected to call for intradermal injection of Bavarian Nordic’s Jynneos vaccine — the only shot approved specifically for monkeypox in the US — as opposed to subcutaneous injection, unnamed sources told both the New York Times and Washington Post on Tuesday.