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.

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.

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.”

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.

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.