FDA ex­perts gun down Alk­er­mes’ pitch for ALKS-5461, slam­ming the com­pa­ny on mul­ti­ple fronts

A large group of out­side ex­perts at the FDA has slapped down Alk­er­mes’ cam­paign to gain an ap­proval for their de­pres­sion drug ALKS-5461, ob­ject­ing to a messy set of da­ta and the way the biotech man­aged the study and re­port­ed the da­ta.

The key ques­tion: Did Alk­er­mes present sub­stan­tial ev­i­dence of the drug’s ef­fi­ca­cy? Twen­ty pan­el mem­bers vot­ed no, with on­ly 3 yes votes, which makes it ex­treme­ly un­like­ly that the FDA’s for­mal de­ci­sion would be any dif­fer­ent. 

A slight ma­jor­i­ty, 13 to 10, vot­ed that the re­searchers had ad­e­quate­ly char­ac­ter­ized the safe­ty of the drug. But that won’t save this drug. By 21 to 2 the com­mit­tee con­clud­ed that Alk­er­mes had failed to sup­port a fa­vor­able ben­e­fit/risk pro­file.

Alk­er­mes’ stock dropped about 9% in af­ter-mar­ket trad­ing Thurs­day.

The FDA’s harsh re­view drew some at­ten­tion from an­a­lysts, in­clud­ing Stifel’s Paul Mat­teis, who not­ed:

It was al­most as if the FDA was so blunt­ly neg­a­tive in its re­marks so as to fos­ter a pan­el vote that cor­rob­o­rat­ed its skep­ti­cal view­point. ALKS is con­duct­ing an­oth­er tri­al for ‘5461 (but re­sults are a ways away) ahead of a 1/31/19 PDU­FA; the fo­cus for the stock is like­ly to shift to ALKS3831.

The set­back like­ly leaves Alk­er­mes back where it was at the be­gin­ning of the reg­u­la­to­ry process, when the FDA ini­tial­ly re­fused to file the ap­pli­ca­tion and then did an about face and opened the door to a re­view. The com­pa­ny has an­oth­er tri­al un­der­way, but now may well be look­ing at a re­quire­ment to mount new, ex­pen­sive and lengthy clin­i­cal tri­als that would like­ly take at least 3 years to com­plete.

Ever­core ISI’s Umer Raf­fat just shook his head at the time­line.

Tech­ni­cal­ly, ALKS has an­oth­er 450 pt Ph 3 on­go­ing on this drug … which re­ports in 2021 as per clin­i­cal­tri­als.gov.  (I sin­cere­ly hope that ALKS is us­ing MADRS-10 at fi­nal time­point in this tri­al … un­like the last Ph 3).  So sure, there’s a chance … but the con­ver­sa­tion has to move past this drug now.

In its pre­sen­ta­tions to­day, agency rep­re­sen­ta­tives high­light­ed the role of a sin­gle “su­per re­spon­der” in in­flu­enc­ing the out­come of one of the tri­als. Late tri­al de­sign changes al­so drew flak. And Alk­er­mes’ in­sis­tence on craft­ing its own ef­fi­ca­cy mea­sures, leav­ing out key points like sui­ci­dal think­ing, was a dis­as­ter.

Here are some of the blunt ex­pert com­ments from to­day:

“I don’t think there’s ev­i­dence this drug works.”

“I’m very con­cerned about the last minute changes.”

“A sin­gle sub­ject dri­ves the re­sults so strong­ly.”

I’m con­cerned about the “lack of trans­paren­cy about in­di­vid­ual sub­ject lev­el da­ta.”

One pan­elist ob­ject­ed to Alk­er­mes’ “cher­ry pick­ing” study da­ta.

“I think there were too many changes along the way.”

“We pay the ul­ti­mate price be­cause we’re the guinea pigs.”

“A lot more needs to be done.”

Alk­er­mes CEO Richard Pops has been tout­ing this drug for years, build­ing its pro­file as a ma­jor new en­try in the field. But Alk­er­mes comes out of this now with its cred­i­bil­i­ty and rep­u­ta­tion for com­pe­tence tar­nished and its pro­jec­tions on fu­ture growth in ques­tion.

Im­age: Richard Pops at an End­points News break­fast event in San Fran­cis­co Jan­u­ary 2017 End­points News

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.

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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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.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Ex-My­lan em­ploy­ee pleads guilty to in­sid­er trad­ing, il­le­gal­ly deal­ing on FDA ap­provals, earn­ings and Up­john merg­er

A former Mylan IT executive pleaded guilty Friday to an insider trading scheme where he bought and sold stock options on another executive’s advice.

Prosecutors secured the plea from Dayakar Mallu, Mylan’s former VP of global operations information technology, after uncovering the plan. Mallu collaborated with an unnamed “senior manager,” the SEC said, to trade options ahead of Mylan public announcements regarding FDA approvals, revenue reports and its merger with the Pfizer generics subsidiary Upjohn. The two subsequently shared profits.

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Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

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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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

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.