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.

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.