Large advertisements for the drug Vivitrol decorate the walls of Grand Central Station on June 15, 2017 in New York City. (Photo: Andrew Lichtenstein via Getty)

FDA slaps down Alk­er­mes for mis­lead­ing Viv­it­rol ads — don't for­get vul­ner­a­bil­i­ty to opi­oid over­dose

The ads piqued in­ter­est as soon as they start­ed ap­pear­ing in 2016: at Grand Cen­tral Sta­tion, on the Red Line in Cam­bridge, and on a bill­board off the New Jer­sey Turn­pike. All showed a young per­son, gen­er­al­ly with his or her arms crossed, and the ques­tion, “what is Viv­it­rol?”

Viv­it­rol’s mak­er, Alk­er­mes, was in the midst of a mar­ket­ing and lob­by­ing cam­paign to pro­mote the an­ti-opi­oid ad­dic­tion drug — a cam­paign that would face sig­nif­i­cant back­lash for tar­nish­ing com­peti­tors de­spite lit­tle ev­i­dence for Viv­it­rol’s su­pe­ri­or­i­ty.

Now a new Viv­it­rol ad­ver­tis­ing cam­paign has prompt­ed a stern warn­ing from the FDA.  The FDA said that Alk­er­mes men­tioned the pos­si­ble ben­e­fits of the drug but failed to dis­close ma­jor risks. Those in­clude an in­creased like­li­hood that a pa­tient will lat­er over­dose on opi­oids.

Richard Pops (End­points file pho­to)

“This vi­o­la­tion is con­cern­ing from a pub­lic health per­spec­tive be­cause it cre­ates a mis­lead­ing im­pres­sion re­gard­ing the over­all safe­ty of  Viv­it­rol,” the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search wrote in a warn­ing let­ter to Alk­er­mes CEO Richard Pops.

The let­ter says that the drug, when used prop­er­ly, can help pre­vent re­lapse to opi­oid de­pen­dence — a sig­nif­i­cant pub­lic health con­cern.  But “those uti­liz­ing Viv­it­rol for the treat­ment of opi­oid de­pen­dence should be made aware of the vul­ner­a­bil­i­ty to po­ten­tial­ly fa­tal over­dose at the end of a dos­ing in­ter­val, af­ter miss­ing a dose, or af­ter dis­con­tin­u­ing Viv­it­rol treat­ment,”

“At­tempts to over­come block­ade may al­so lead to fa­tal over­dose,” it adds.

It’s not clear where the ad ap­peared, but it is tar­get­ed to­wards those work­ing in the crim­i­nal jus­tice sys­tem and di­rects them to Viv­it­rol­ It shows a judge and a bald man in a sweat­shirt ex­chang­ing a slim stack of pa­pers over her bench.

(via FDA)

Click on the im­age to see the full-sized ver­sion

“The crim­i­nal jus­tice sys­tem is chal­lenged with re­spond­ing to the opi­oid epi­dem­ic,” it reads. “Their path to re­cov­ery can be­gin with your help,”

Un­der “im­por­tant safe­ty in­for­ma­tion,” it lists what Viv­it­rol is in­di­cat­ed for and in­di­cat­ed against, but it does not men­tion the fa­tal risk the drug pos­es.

Viv­it­rol, which is sci­en­tif­i­cal­ly known as nal­trex­one for ex­tend­ed-re­lease in­jectable sus­pen­sion, blocks the ef­fects of opi­oids from out­side the body for around 28 days. But as that block­ade weak­ens and ul­ti­mate­ly van­ish­es, pa­tients can re­spond to low­er dos­es of opi­oids than they oth­er­wise would.

A pa­tient who takes a dose of opi­oids they pre­vi­ous­ly would have tol­er­at­ed could then over­dose.  Pa­tients that try to over­come the block while the drug is in ef­fect may al­so over­dose.

There is less da­ta out on Viv­it­rol than on oth­er opi­oid de­pen­den­cy drugs buprenor­phine and methadone, but in 2018 a pa­per in Drug Safe­ty at­tempt­ed to an­a­lyze the risk of over­dose.

Out of 263 ad­verse events from Viv­it­rol that re­searchers ob­tained through a pub­lic records re­quest, they were left with 52 deaths that fit an over­dose de­scrip­tion. Of those, 5 oc­curred in the 28 days, mean­ing the pa­tient had tried to over­come the block. The me­di­an time of death was 46 days af­ter in­jec­tion and the av­er­age was 56.3 days — or a few weeks af­ter the last shot’s block­ing ef­fects wore off.

Alk­er­mes strong­ly dis­put­ed the re­sults. The au­thors stopped short of an­nounc­ing causal­i­ty, but they said com­pa­nies and the gov­ern­ment need to fol­low the is­sue more close­ly and warn pa­tients bet­ter, as at least around half will dis­con­tin­ue treat­ment.

“We’re say­ing that if you’re go­ing to be putting peo­ple on it, there’s a time pe­ri­od af­ter you take them off of it or they come off it where you need to do a bet­ter job of re­mind­ing them of their risk,” Nabarun Das­gup­ta, study co-au­thor and a re­search sci­en­tist at the Uni­ver­si­ty of North Car­oli­na, told ProP­ub­li­ca last year.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Vi­da Ven­tures co-leads Dyne's $115M megaround for next-gen oli­go ther­a­pies aimed square­ly at mus­cles

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that it’s got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.

Eli Lil­ly teams with Pieris on HER2+ tu­mors; Op­di­vo + Yer­voy best chemo in mesothe­lioma

Despite the FDA putting a partial clinical hold on its lead program only a few weeks ago, Boston-based Pieris Pharmaceuticals is plowing forward with a new collaboration.

Pieris will work with Eli Lilly to further advance studies on PRS-343, a 4-1BB/HER2 bispecific for HER2-positive tumors, in combination with the latter’s ramucirumab and paclitaxel for the second-line treatment of patients with HER2-positive gastric cancer in a single-arm, Phase II study.

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China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

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Anap­tys­Bio's etokimab pro­vides more dis­ap­point­ing re­sults, rais­ing ques­tions about com­pound's fu­ture

The lead program for AnaptysBio’s in-house pipeline has hit another setback.

Etokimab, an IL-33 inhibitor, did not achieve statistically significant improvement in a Phase II trial for patients suffering from chronic rhinosinusitis with nasal polyps. Researchers measured the individuals’ bilateral nasal polyps score and sino-nasal outcome test, finding that neither improved upon a placebo after both four- and eight-week time markers, though they did demonstrate improvement over baseline levels of the examinations.

Gallia Levy, Spark CMO (Roche)

Spark Ther­a­peu­tics nabs new CMO from Genen­tech, fill­ing a ma­jor post-merg­er de­par­ture

Spark Therapeutics is getting a new CMO from their new owners.

The gene therapy company-turned-subsidiary has named Gallia Levy, who had been running rare blood disorders — including clinical development for their blockbuster-potential hemophilia antibody Hemlibra for Roche’s big biotech sub Genentech — to run medical affairs.

The appointment is a fitting one. Roche spent $4.8 billion to acquire Spark last year in large part to get their hands on their hemophilia gene therapy, SPK-8011, and expand the toe-hold Hemlibra gave them in an crowded hemophilia space.  It’s also a somewhat ironic appointment: The FTC held up the Spark acquistions for nearly a year, reportedly over concerns about the anti-trust implications of Roche owning both a top chronic treatment in Hemlibra and a top one-time treatment in Spark’s gene therapy.

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