Pos­i­tive PhI­II can't sal­vage Mer­ck­'s anace­trapib, now rel­e­gat­ed to the scrap heap

There will be no CETP heart drug mir­a­cle in the works at Mer­ck.

The phar­ma gi­ant looked over a set of pos­i­tive but trou­ble­some Phase III da­ta for its drug anace­trapib and con­clud­ed to­day that they will rel­e­gate it to the same grave­yard that has greet­ed every oth­er CETP heart drug so far.

The de­ci­sion un­der­scores a tidal shift in drug de­vel­op­er’s stan­dards for launch­ing a big new drug in­to a ma­jor mar­ket, where the da­ta has to point to a com­pelling mar­ket op­por­tu­ni­ty. Fail­ing that, mar­gin­al drugs don’t stand a chance, even if they might pass muster at the FDA.

“Un­for­tu­nate­ly, af­ter com­pre­hen­sive eval­u­a­tion, we have con­clud­ed that the clin­i­cal pro­file for anace­trapib does not sup­port reg­u­la­to­ry fil­ings,” said Roger Perl­mut­ter, pres­i­dent of Mer­ck Re­search Lab­o­ra­to­ries. “Dur­ing the past half-cen­tu­ry, Mer­ck has made nu­mer­ous, im­por­tant con­tri­bu­tions to the treat­ment of car­dio­vas­cu­lar dis­ease. Our work in car­dio­vas­cu­lar re­search con­tin­ues.”

Once up­on a time, CETP of­fered a bright prospect for some of the world’s biggest de­vel­op­ers, dri­ving mas­sive late-stage stud­ies in search of huge mar­kets that would run for years and gob­ble hun­dreds of mil­lions of dol­lars. Then ri­vals at Roche, Pfiz­er and Eli Lil­ly all fell by the way­side with poor out­comes.

Roger Perl­mut­ter

Even­tu­al­ly, Mer­ck was left to car­ry on to the end. But when it an­nounced stun­ning­ly pos­i­tive da­ta ear­li­er this year, the phar­ma gi­ant care­ful­ly re­frained from any vic­to­ry cel­e­bra­tions. The da­ta un­der­scored the rea­sons for their low-key re­view.

Across the study pop­u­la­tion of more than 30,000 pa­tients, the drug arm demon­strat­ed a 9% re­duc­tion in the risk of a com­pos­ite of ma­jor coro­nary events: coro­nary death, my­ocar­dial in­farc­tion or coro­nary re-vas­cu­lar­iza­tion. That trans­lates in­to a lean and hard-to-mar­ket 1-point dif­fer­ence — a sig­nif­i­cant but so-so 10.8% com­pared to 11.8% — in the rate of events. And it was a con­sis­tent re­sult across the sub-groups that the re­searchers want­ed to fol­low.

Af­ter a bit more than 4 years of treat­ment on av­er­age, non-HDL cho­les­terol lev­el de­clined by 17 mg/dL; good HDL lev­els rose by 43 mg/dL.

The bad news:

Drag­ging be­hind on ex­pect­ed rates of pre­sumed is­chemic stroke, re­searchers con­clud­ed that the drug missed the key sec­ondary end­point of their com­pos­ite of ma­jor ath­er­o­scle­rot­ic events: my­ocar­dial in­farc­tion, coro­nary death or pre­sumed is­chemic stroke.

These days, that spells a drug that can get ap­proved but nev­er find a mar­ket. And that’s not good enough for the likes of Mer­ck.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.

Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.