An­tipsy­chot­ic from Lund­beck, Ot­su­ka flops again in PhI­II tri­als — this time in bipo­lar pa­tients

New Lund­beck CEO Deb­o­rah Dun­sire has more bad news to con­tend with, five months in­to her ap­point­ment. The Dan­ish drug­mak­er — which is bat­tling with gener­ics eat­ing in­to sales of three key drugs and a re­cent set­back for schiz­o­phre­nia — on Thurs­day said a pair of piv­otal tri­als failed to show its block­buster an­tipsy­chot­ic drug, br­ex­pipra­zole, helped pa­tients with bipo­lar dis­or­der.

Deb­o­rah Dun­sire

The drug, dis­cov­ered by Ot­su­ka and part­nered with the Japan­ese com­pa­ny, is al­ready ap­proved for use in ma­jor de­pres­sion and schiz­o­phre­nia and is sold un­der the brand name Rex­ul­ti.

The two, 3-week tri­als test­ed the drug ver­sus a place­bo in 650 bipo­lar I pa­tients who ex­pe­ri­enced an acute man­ic episode that re­quired hos­pi­tal­iza­tion. The main goal of ei­ther tri­al was to show br­ex­pipra­zole in­duced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment on a com­mon rat­ing scale used to as­sess ma­nia symp­toms based on a pa­tient’s sub­jec­tive re­ports and clin­i­cian ob­ser­va­tions.

Most tri­als test­ing drugs to treat psy­chi­atric dis­or­ders fall prey to an in­flat­ed place­bo ef­fect. This case was no dif­fer­ent — in both stud­ies, a high­er-than-ex­pect­ed place­bo ef­fect was de­tect­ed, the com­pa­nies said.

The duo — who did not break out the num­bers re­flect­ing the fail­ure on Thurs­day — are con­duct­ing an analy­sis of the da­ta, and will con­se­quent­ly de­ter­mine the next steps for the pro­gram.

Leerink an­a­lysts said they were sur­prised by the fail­ure, con­sid­er­ing both Abil­i­fy and Al­ler­gan’s $AGN Vray­lar — two oth­er par­tial ag­o­nists on the D2/D3 re­cep­tors — have demon­strat­ed ef­fi­ca­cy in this in­di­ca­tion, as well as var­i­ous oth­er an­tipsy­chotics cur­rent­ly be­ing used to treat bipo­lar ma­nia. “Amongst the pos­si­ble psy­chi­a­try in­di­ca­tions that could be pur­sued in this space, Bipo­lar I man­ic episodes is one of the more “low hang­ing fruit” in­di­ca­tions, as it is of­ten the ini­tial bipo­lar spec­trum ap­proval that al­lows prod­ucts to launch or ex­pand in psy­chi­a­try – all of which adds to our sur­prise here…how­ev­er, we will not make any changes to our sales es­ti­mates for Rex­ul­ti be­cause we don’t in­clude much sales for this in­di­ca­tion any­way,” they wrote.

In 2017, two late-stage stud­ies test­ing br­ex­pipra­zole for ag­i­ta­tion trig­gered by Alzheimer’s de­men­tia threw up mixed da­ta, with one study suc­cess­ful and the oth­er deemed a fail­ure. Dun­sire, who took the reins in Sep­tem­ber, was dealt a big set­back in Oc­to­ber with a Phase III fail­ure of the com­pa­ny’s schiz­o­phre­nia drug can­di­date, Lu AF35700. How­ev­er, she had some cheer in No­vem­ber when br­ex­pipra­zole yield­ed suc­cess in a mid-stage study in pa­tients with PTSD when giv­en in com­bi­na­tion with the an­ti­de­pres­sant ser­tra­line (Zoloft).

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Sanofi takes a $260M hit to ex­tri­cate it­self from a dis­as­trous al­liance with Lex­i­con

Sanofi spent $300 million in cash to get into a $1.7 billion alliance with Lexicon on their SGLT1/2 diabetes drug sotagliflozin. And now that the drug has been spurned by the FDA after burning through a program that provided mixed late-stage data and a late shot at a last-place finish, the French pharma giant is forking over another $260 million to get out of the deal.

Sanofi’s unhappiness was already apparent when the company — now under new CEO Paul Hudson — posted a statement back in July that they were dropping the deal. But it wasn’t that simple. 

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.