Richard Pops (Photographer: Patrick T. Fallon/Bloomberg via Getty Images)

Alk­er­mes wins FDA nod for com­bo med with an­tipsy­chot­ic olan­za­p­ine — this time with­out the weight gain red flags

Alk­er­mes has had a rough go in the past few years, mak­ing the de­ci­sion to slice away a healthy por­tion of its R&D work­force last year af­ter a ma­jor set­back in de­pres­sion. The drug­mak­er placed a lot of hope in an­tipsy­chot­ic drug ALKS 3831 to turn things around, and af­ter a win­ning ad­comm late last year that bet is fi­nal­ly pay­ing off.

The FDA on Tues­day ap­proved Alk­er­mes’ Ly­balvi (olan­za­p­ine and sami­dor­phan) to treat schiz­o­phre­nia and bipo­lar 1 dis­or­der, the com­pa­ny said in a re­lease.

The drug was ap­proved as a main­te­nance monother­a­py, or for the acute treat­ment of man­ic or mixed episodes as a monother­a­py or ad­junct to lithi­um or val­proate, Alk­er­mes said. Ly­balvi is a com­bi­na­tion of nov­el chem­i­cal sami­dor­phan and an­tipsy­chot­ic olan­za­p­ine, an ag­ing an­tipsy­chot­ic con­sid­ered one of the field’s most ef­fec­tive de­spite pre­vi­ous red flags over pa­tients’ weight gain.

But with the new for­mu­la­tion, Alk­er­mes thinks it has cracked the code on those pri­or olan­za­p­ine is­sues. The agency based its re­view on ex­pan­sive da­ta from Alk­er­mes’ EN­LIGHT­EN pro­gram, which in­clud­ed 27 clin­i­cal stud­ies, in­clud­ing 18 stud­ies test­ing Ly­balvi and nine study­ing sami­dor­phan alone, the com­pa­ny said. Among those, EN­LIGHT­EN-2 churned out da­ta show­ing schiz­o­phre­nia pa­tients on Ly­balvi post­ed sig­nif­i­cant­ly less weight gain than pa­tients tak­ing olan­za­p­ine alone.

Alk­er­mes $ALKS shares were trad­ing up about 6% be­fore the bell Tues­day.

Ly­balvi will come with a black box warn­ing for in­creased risk of mor­tal­i­ty in el­der­ly pa­tients with de­men­tia-re­lat­ed psy­chosis, ac­cord­ing to its la­bel. That warn­ing is tied to re­port­ed cas­es of cere­brovas­cu­lar side ef­fects in clin­i­cal tri­als, in­clud­ing stroke and tran­sient is­chemic at­tack. The drug will come with con­traindi­ca­tions for pa­tients tak­ing opi­oids or who are un­der­go­ing acute opi­oid with­draw­al.

The drug­mak­er ex­pects Ly­balvi to hit the mar­ket in the Oc­to­ber/No­vem­ber time­frame and plans to lean on its ex­ist­ing com­mer­cial in­fra­struc­ture from mar­ket­ed an­tipsy­chot­ic Aris­ta­da to grease the wheels for the new drug’s suc­cess­ful launch, ac­cord­ing to a re­lease. The team will add 50 sales reps to that Aris­ta­da “core,” CCO Todd Nichols said on a Tues­day morn­ing call with in­vestors, as it works to ramp up com­mer­cial man­u­fac­tur­ing and fi­nal­ize its pro­mo­tion­al claims pri­or to a full roll­out at launch.

Alk­er­mes didn’t re­lease the list price, say­ing it was wait­ing on pay­er ne­go­ti­a­tions pri­or to launch.

An­tipsy­chotics is an un­usu­al mar­ket, with most first-line scripts dom­i­nat­ed by gener­ics al­though a pro­por­tion of pa­tients even­tu­al­ly cy­cle through those ear­ly drugs. That means the po­ten­tial mar­ket for Ly­balvi will like­ly take a while to de­vel­op, with Alk­er­mes pre­dict­ing around $10 mil­lion in sales by the end of the year.

“We have es­tab­lished a pro­file that there will be a path­way to ac­cess at launch, but it will de­vel­op over time,” Nichols said. “They’re most like­ly go­ing to have to step through one or two gener­ics be­fore ac­cess, and we’re pre­pared for that.”

Ly­balvi, for­mer­ly dubbed ALKS 3831, faced an FDA ad­vi­so­ry com­mit­tee in Oc­to­ber dur­ing which the ques­tion of a po­ten­tial REMS was pro­posed for the drug. The com­mit­tee vot­ed 11-6 that po­ten­tial la­bel­ing was enough to mit­i­gate risk, a big draw for Alk­er­mes in the heav­i­ly reg­u­lat­ed an­tipsy­chot­ic space.

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In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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BREAK­ING: Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck 5 years ago, where the soft spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

No­vavax shares shred­ded as Covid vac­cine sales fall more than 90% in Q2

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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FDA's vac­cine ad­comm to re­view first fe­cal trans­plant to treat C. dif­fi­cile in­fec­tions

Back in 2018, Swiss drugmaker Ferring Pharmaceuticals made a big bet on Minnesota-based Rebiotix, buying up the company for its experimental poop-based drug implant to treat an infection caused by C. difficile, a potentially dangerous bacteria, in a new way.

Four years later, Ferring’s fecal microbiota transplant, dubbed RBX2660 or Rebyota, will face the FDA’s adcomm of outside vaccine experts on Sept. 22, debating whether the agency should license the transplant as a treatment for adults following antibiotic treatment for recurrent C. difficile infection.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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