Mer­ck and the FDA have en­gaged in a high-noon stand­off over check­point in­hibitor Keytru­da in triple-neg­a­tive breast can­cer af­ter the agency round­ly panned its re­sults in high-risk pa­tients. Now, with a de­ci­sive ad­comm sup­port­ing its crit­i­cisms, the FDA has shown Keytru­da the door in that in­di­ca­tion.

The FDA slapped Keytru­da with a CRL in high-risk triple-neg­a­tive breast can­cer af­ter the agency’s On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee hand­ed out a rather gen­tle slap­down on the I/O drug’s ap­pli­ca­tion last month, Mer­ck said Mon­day.

Keytru­da’s chances as monother­a­py af­ter a reg­i­men of Keytru­da and chemo and surgery in triple-neg­a­tive breast can­cer were al­ways a long­shot af­ter the FDA of­fered a sting­ing re­buke of the drug’s piv­otal dataset, which it called “ques­tion­able” giv­en im­ma­ture OS da­ta and some wishy-washy ef­fi­ca­cy num­bers, ac­cord­ing to ODAC brief­ing doc­u­ments at the time.

What re­al­ly riled up the agency, how­ev­er, was that they ex­plic­it­ly asked Mer­ck not to sub­mit for ap­proval af­ter ex­press­ing their con­cerns with the ma­tu­ri­ty of the dataset af­ter mul­ti­ple meet­ings. The CRL doesn’t af­fect Keytru­da’s ap­proval as a com­bi­na­tion ther­a­py with chemo in lo­cal­ly ad­vanced, PD-1 ex­press­ing TNBC tu­mors that are metasta­t­ic or can­not be sur­gi­cal­ly re­moved.

The ba­sis for Mer­ck’s sub­mis­sion was KEYNOTE-522, which test­ed Keytru­da as a post-sur­gi­cal monother­a­py fol­low­ing a com­bo of Keytru­da and plat­inum-based chemother­a­py. The study’s event-free sur­vival pri­ma­ry end­point over place­bo was too im­ma­ture to judge — a quick red flag — as re­searchers hadn’t watched pa­tients long enough af­ter treat­ment to de­ter­mine EFS and OS. At the time of third check-in, just 53% of tar­get­ed EFS events had oc­curred and 32% of OS events.

The agency al­so pushed back on the study’s pCR co-pri­ma­ry end­point, which Keytru­da hit, call­ing ef­fi­ca­cy over place­bo “small.”

The 10-0 ODAC vote, how­ev­er, wasn’t a nail in the cof­fin. The ad­vi­so­ry com­mit­tee ad­vo­cat­ed wait­ing out fi­nal safe­ty fig­ures, and Mer­ck said an­oth­er in­ter­im look-in on the KEYNOTE-522 da­ta was com­ing up in the third quar­ter.

Does any of that “wait-and-see” men­tal­i­ty mean the FDA will change its mind and wel­come Keytru­da back in these pa­tients? That’s un­clear. But a win on EFS and OS could be enough to swing a vote giv­en the FDA’s re­cent his­to­ry of re­ward­ing drugs that don’t hit the pri­ma­ry end­point in piv­otal stud­ies. Call­ing an ad­comm on da­ta it seemed nev­er like­ly to ap­prove, how­ev­er, looked a lot like the FDA and OCE di­rec­tor Richard Paz­dur pub­licly putting an overzeal­ous drug­mak­er in the penal­ty box.

Mer­ck, for its part, found the drug’s in­ter­im sur­vival da­ta to show a “strong and durable” trend, the drug­mak­er said in Feb­ru­ary.

Ed­i­tor’s Note: This sto­ry has been up­dat­ed to clar­i­fy de­tails of KEYNOTE-522’s de­sign.

The FDA on Tuesday released a warning letter sent earlier this month to the Mason, OH-based site of Procter & Gamble Manufactura, raising questions about the list of ingredients on the label and in the electronic filing.

The warning says that for P&G’s over-the-counter Vicks Nyquil Severe Hot Remedy Cold and Flu Plus Congestion, there’s a “mismatched” list of active ingredients between the labeling and the electronic listing file. The listing file for the active ingredients did not match the active ingredients in the electronic file.

The Federal Trade Commission has gotten involved in a patent feud over Supernus’ Parkinson’s drug Apokyn, a case the agency said may have ‘‘significant implications” for patients who rely on the drug.

Sage Chemical won the first generic approval for its Apokyn formulation (also known as apomorphine hydrochloride injection) back in 2022. The non-ergoline dopamine agonist is approved to treat Parkinson’s symptoms during “off episodes,” such as difficulty moving, tremors and intense cramping. However, regulators specified that the approval pertained to the generic drug cartridges only, not the injector pen required for administration.

The White House’s Office of Science and Technology Policy (OSTP) last year sought to find ways to better coordinate large-scale clinical trials in the US — as the UK lead by example during the pandemic — especially for these emergency clinical trials.

The lobbying group PhRMA Tuesday called for more clinical trial diversity in underserved areas, including by making participation less of a burden, and expanding eligibility criteria when appropriate.