Bris­tol-My­ers star Op­di­vo fails sur­vival test in a matchup with Nex­avar aimed at shak­ing up the big HCC mar­ket

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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Work taking place in the clean rooms at Vor (Credit: Vor)

Vor Bio opts to keep man­u­fac­tur­ing op­er­a­tions in-house for de­vel­op­ing stem cell, CAR-T ther­a­pies

While it is not uncommon for a biotech to go down the route of having the product manufactured by a contract organization, one small biotech is looking to keep its card close to its chest.

Vor Biopharma has started manufacturing operations at an in-house facility at its HQ in Cambridge, MA after beginning construction last summer.

According to the biotech, the facility aims to develop Vor’s hematopoietic stem cells (eHSCs) and CAR-T therapies for patients with blood cancers. The site will initially manufacture a clinical supply of its candidate VCAR33allo to support its IND, which is slated to be submitted in the first half of next year. It also plans to transfer the production of VOR33 to the facility. Vor is getting to work quickly as engineering runs for VCAR33allo has started this week.

Tar­sus looks to raise aware­ness of eye­lid mite dis­ease in cam­paign aimed at eye­care spe­cial­ists

Eyelid mite disease may be “gross” but it’s also fairly common, affecting about 25 million people in the US.

Called demodex blepharitis, it’s a well-known condition among eyecare professionals, but they often don’t always realize how common it is. Tarsus Pharmaceuticals wants to change that with a new awareness campaign called “Look at the Lids.”

The campaign and website debut Thursday — just three weeks after Tarsus filed for FDA approval for a drug that treats the disease.

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An­oth­er Avastin biosim­i­lar joins the par­ty as Roche's grip on the mar­ket loosens

Avastin has attracted quite the crowd of biosimilars in recent years, and one more pharma company has elbowed its way in.

Regulators on Wednesday approved Celltrion’s biosimilar Vegzelma in six cancer types, including metastatic colorectal cancer; recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC); recurrent glioblastoma; metastatic renal cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube or primary peritoneal cancer.

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Elisabeth Stampa, Medicines for Europe president

As win­ter ap­proach­es, a Eu­ro­pean gener­ics group rais­es alarm over en­er­gy prices for man­u­fac­tur­ers

While colder temperatures are fast approaching, the situation surrounding the rise of energy prices in Europe is hitting businesses of every kind, including generic drug manufacturers.

Medicines for Europe, a group that represents the generic industry on the continent, sent a letter addressed to energy ministers and commissioners concerning inflation and the costs of energy on the supply of generic medicines.