UP­DAT­ED: NewAms­ter­dam Phar­ma res­ur­rects Am­gen's old CETP drug with plans to jump in­to PhI­II this year

Eli Lil­ly thought it found the “holy grail” a decade ago with a CETP in­hibitor that low­ered bad cho­les­terol and raised good cho­les­terol, with oth­ers like Mer­ck, Am­gen, Roche and Pfiz­er jump­ing in the race as well. But when study af­ter study showed the new class of drugs didn’t curb car­dio­vas­cu­lar dis­ease, Big Phar­ma large­ly aban­doned their ef­forts.

NewAms­ter­dam Phar­ma CEO Michael David­son saw an op­por­tu­ni­ty last year to res­ur­rect Am­gen’s old drug — one of the few that didn’t make it to piv­otal stud­ies. And on Wednes­day, he un­veiled the first pos­i­tive Phase II re­sults.

Michael David­son

When ad­min­is­tered along with statins, a 10 mg dose reg­i­men of obice­trapib low­ered pa­tients’ bad cho­les­terol (LDL) lev­els by a me­di­an 51% com­pared to 7% in the place­bo arm, meet­ing the study’s pri­ma­ry end­point, David­son said, hit­ting a p-val­ue of p=0.0001. Mean de­crease in LDL cho­les­terol was 44% in the obice­trapib arm, ver­sus 4% in the place­bo armac­cord­ing to the com­pa­ny, a dif­fer­ence which hit a p-val­ue of p<0.0001.

“We learned a lot from those fail­ures,” he said of oth­er CETP at­tempts. “And now we have a much more ef­fec­tive LDL-low­er­ing drug, more than twice as ef­fec­tive in low­er­ing LDL, and al­so based on our da­ta so far (it’s) ex­treme­ly safe.”

David­son sug­gest­ed that pri­or re­searchers mis­un­der­stood the drug’s mech­a­nism: While in­ves­ti­ga­tors pre­vi­ous­ly thought CETP in­hibitors were ben­e­fi­cial be­cause they boost­ed good cho­les­terol (HDL) by large amounts, they now think it’s the re­duc­tion to bad cho­les­terol that leads to ben­e­fit.

All 120 pa­tients in the Phase II tri­al, dubbed ROSE, were al­ready tak­ing max­i­mal dos­es of high-in­ten­si­ty statins, which work by block­ing a sub­stance your body needs to make cho­les­terol, David­son said. Pa­tients were di­vid­ed in­to three co­horts: a 5 mg group, a 10 mg group, and a place­bo group. Both dose groups met the pri­ma­ry end­point, ac­cord­ing to David­son, who’s work­ing to ini­ti­ate Phase III tri­als in Q4. They’re al­so plan­ning to test obice­trapib in com­bi­na­tion with the al­ready ap­proved cho­les­terol-low­er­ing drug eze­tim­ibe.

“We proved that it’s just as ef­fec­tive, if not more ef­fec­tive, on top of high-in­ten­si­ty statins. So that’s ex­act­ly the type of pa­tient pop­u­la­tion that the FDA wants to see for fu­ture de­vel­op­ment of LDL-c-low­er­ing ther­a­pies,” he said.

Am­gen shelled out $300 mil­lion up­front and over $1 bil­lion in mile­stones to buy out Dez­i­ma Phar­ma and its sole prod­uct, obice­trapib, back in 2015. But the phar­ma end­ed up shelv­ing the can­di­date just two years lat­er, short­ly af­ter Eli Lil­ly, Pfiz­er, Roche and Mer­ck all walked away from their own CETP drugs.

Last Au­gust, David­son snagged the can­di­date from Am­gen for an undis­closed amount. If he could flip it around for an FDA OK, he said at the time, it would be the “crown­ing” achieve­ment of his ca­reer. In Jan­u­ary, a lengthy syn­di­cate led by Morn­ing­side Ven­tures and For­bion put $196 mil­lion in­to a Se­ries A to get the com­pa­ny start­ed.

If all goes well, NewAms­ter­dam thinks obice­trapib could treat dis­eases like Alzheimer’s and di­a­betes. The team is plan­ning to kick off an Alzheimer’s tri­al in Sep­tem­ber, and they’ll eval­u­ate di­a­betes end­points through­out the up­com­ing Phase III pro­gram.

“We feel we re­al­ly have the right drug, the right com­pound that now can ful­ly val­i­date what’s al­ready been ge­net­i­cal­ly val­i­dat­ed as a tar­get to low­er LDL and car­dio­vas­cu­lar risk,” David­son said.

This ar­ti­cle has been up­dat­ed to in­clude more da­ta pro­vid­ed by NewAms­ter­dam. 

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.

Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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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).

Vicente Anido (University of West Virginia via YouTube)

Aerie fires CEO af­ter lead pro­gram flop, com­ments about pri­ma­ry end­points be­ing 'not re­quired'

Aerie Pharmaceuticals CEO Vicente Anido has left the company less than a week after trying to chart a Phase III study in the wake of a serious Phase IIb flop.

Anido’s last day at Aerie was Friday, the biotech announced in a news release Tuesday morning, and Benjamin McGraw is taking his place in an interim role. The now former CEO was terminated without cause, according to an SEC filing.

The board has started looking for a full-time chief to take his place.

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