Bris­tol-My­ers Squibb has suf­fered an­oth­er painful set­back in its years-long quest to ex­pand the reach of Op­di­vo. The phar­ma gi­ant this morn­ing not­ed that their Check­mate-459 study com­par­ing Op­di­vo with Bay­er’s Nex­avar in front­line cas­es of he­pa­to­cel­lu­lar car­ci­no­ma — the most com­mon form of liv­er can­cer — failed to hit the pri­ma­ry end­point on over­all sur­vival.

This was a sig­nif­i­cant mile­stone in Bris­tol-My­ers’ tal­ly of PD-1 cat­a­lysts this year. Nex­avar (so­rafenib) has been the stan­dard of care in front­line HCC for the past decade, though Op­di­vo has been mak­ing head­way in sec­ond-line HCC cas­es, where it’s go­ing toe-to-toe with Bay­er’s Sti­var­ga (re­go­rafenib) af­ter re­cent ap­provals shook up the mar­ket.

The OS rate on Op­di­vo fell well short of sta­tis­ti­cal sig­nif­i­cance, with a p val­ue of 0.0752. We’ll have to wait for an up­com­ing sci­ence con­fer­ence to get the full pic­ture.

Bris­tol-My­ers shares $BMY were down 4.5% ahead of the open­ing bell Mon­day as in­vestors re­act­ed to the news that the com­pa­ny is sell­ing Ote­zla to sat­is­fy reg­u­la­tors ahead of its big Cel­gene buy­out.

Re­searchers looked for a sil­ver lin­ing in the lat­est cut of the da­ta onOp­di­vo, say­ing “the re­sults showed a clear trend to­wards im­prove­ment in OS for pa­tients treat­ed with Op­di­vo com­pared to so­rafenib (Nex­avar), a cur­rent stan­dard of care.”

Bruno San­gro Clíni­ca Uni­ver­si­dad de Navar­ra

“We are en­cour­aged by the promis­ing ef­fi­ca­cy and safe­ty trends seen with Op­di­vo in Check­Mate-459, es­pe­cial­ly as HCC is a dev­as­tat­ing and dif­fi­cult-to-treat can­cer, for which there have been no sig­nif­i­cant ad­vances over so­rafenib, a stan­dard treat­ment, in more than a decade,” said Bruno San­gro, head of the liv­er unit, Clíni­ca Uni­ver­si­dad de Navar­ra, Pam­plona, Spain.

But an­a­lysts saw the down­side clear­ly. Vamil Di­van from Cred­it­Su­isse not­ed: “While the tri­al showed a trend to­wards an over­all sur­vival ben­e­fit, the lack of sta­tis­ti­cal sig­nif­i­cance opens the door for com­peti­tors such as Mer­ck, Roche and As­tra to be­come the dom­i­nant play­er(s) in this in­di­ca­tion with the var­i­ous com­bi­na­tion tri­als they are cur­rent­ly run­ning.”

Michael Schmidt at SVB Leerink re­cent­ly not­ed:

In the US, Op­di­vo is gain­ing rapid mar­ket share in 2nd line HCC dri­ven by an ag­gres­sive mar­ket­ing ef­fort by BMY and mas­sive free sam­pling with some off-la­bel use not­ed in front-line pa­tients which is sup­port­ed by strong CM-040 re­sults. In Eu­rope, re­go­rafenib is ex­pect­ed to re­main the pre­ferred 2nd line agent in the near term, giv­en dif­fer­ences in treat­ment pat­tern and pref­er­ences.

Bris­tol-My­ers is by no means fin­ished here, with more re­sults ex­pect­ed on their com­bo with the CT­LA-4 Yer­voy. That match-up, though, has al­ready failed in small cell lung can­cer while in­ves­ti­ga­tors have had to deal with a strong push­back from the FDA in their quest to use high tu­mor mu­ta­tion­al bur­den de­f­i­n­i­tions to de­fine a new ap­proach to iden­ti­fy­ing lung can­cer pa­tients most like­ly to re­spond to Op­di­vo.

Mer­ck, mean­while, has fa­mous­ly pressed ahead in its suc­cess­ful dri­ve to gain the lead po­si­tion in the race to com­mand the PD-1 field. Both Keytru­da and Op­di­vo, though, are ex­pect­ed to re­main the two dom­i­nant drugs in their field for some time.

Biohaven is at risk of making a habit of disappointing its investors. 

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

→ On the same day it announced a $17.5 million Series C, life sciences and health data company Seer unveiled that it had lured former FDA commissioner and ex-CMS administrator Mark McClellan on to its board. “Mark’s deep understanding of the health care ecosystem and visionary insights on policy reform will be crucial in informing our thinking as we work to bring our liquid biopsy and life sciences products to market,” said Seer chief and founder Omid Farokhzad in a statement.

Gilead CEO Daniel O’Day’s new task hunting up a CSO for the company isn’t stopping the industry’s dominant antiviral player from doing pipeline deals.

The big biotech today snapped up 3 preclinical antiviral programs from pharma giant Novartis, with drugs promising to treat human rhinovirus, influenza and herpes viruses. We don’t know what the upfront is, but the back end has $291 million in milestones baked in.