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

Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Flu Virus (Source: CDC)

FDA ex­pands Xofluza ap­proval as Roche strug­gles to catch loom­ing flu mar­ket

As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.

Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.

EMA backs sev­en ther­a­pies, in­clud­ing Mer­ck­'s Ebo­la vac­cine

The first-ever Ebola vaccine is on the precipice of approval after the European Medicine’s Agency (EMA) backed the Merck product in this week’s roster of recommendations.

The drugmaker $MRK began developing the vaccine, christened Ervebo, during the West African outbreak that occurred between 2014 and 2016, killing more than 11,000.

The current outbreak in the Democratic Republic of Congo (DRC) has shown case fatality rates of approximately 67%, the agency estimated. Earlier this year, the WHO declared the outbreak — which so far has infected more than 3,000 people — a public health emergency of international concern.

Ronald Herb­st fol­lows Med­Im­mune ex­o­dus to Pyx­is CSO post; Jeff God­dard to suc­ceed CEO of AIT Bio­science

→ The outflow of top execs from MedImmune continues to fill the leadership ranks of smaller biotechs. The latest to take off is Ronald Herbst, the head of oncology research, who’s assuming the CSO post at Pyxis Oncology.  

Herbst was part of the old MedImmune organization AstraZeneca CEO Pascal Soriot restructured earlier this year, reorganizing the company and eliminating the storied subsidiary as a separate organization.

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Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.

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