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.

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.

As he awaits a tight Senate vote, Rob Califf, President Joe Biden’s nominee to be the next FDA commissioner, is signaling where the agency may move on accelerated approvals if he takes over at FDA.

Building off comments from his Senate confirmation hearing, in which Califf said that he’s “a fan of accelerated approval” but the US needs a better system to evaluate these drugs once they’re on the market, the nominee raised questions about how well the current structure serves patients.

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.