Al­ny­lam slammed af­ter pa­tient death forces in­ves­ti­ga­tors to halt dos­ing of fi­tusir­an, rais­ing new safe­ty fears

Al­ny­lam $AL­NY has been slammed by an­oth­er round of safe­ty fears, forced to sus­pend all treat­ment with fi­tusir­an af­ter a pa­tient died from a blood clot in a Phase II he­mo­phil­ia A study.

Al­ny­lam ex­ecs plan to re­sume dos­ing as soon as pos­si­ble, but the com­pa­ny has been hob­bled by deaths be­fore that re­cent­ly KO’d a top pro­gram at the RNAi group. New safe­ty ques­tions about a key late-stage drug like this is the last thing that Al­ny­lam wants to grap­ple with now.

Al­ny­lam will now put plans to start the Phase III AT­LAS study on hold un­til this is re­solved, with the on­go­ing Phase II OLE study side­lined for now. And shares of the biotech dropped 11% on the news Thurs­day morn­ing.

There’s no telling how deep the dam­age could be, though. As Paul Mat­teis at Leerink not­ed, blood clot­ting has been a con­cern for some time among the thought lead­ers in the field. And even if Al­ny­lam gets past this hur­dle, an in­ci­dent like this could crip­ple mar­ket ex­pec­ta­tions.

While we look to more col­or re­gard­ing AL­NY’s pre­lim­i­nary plans on the com­pa­ny’s call this morn­ing, our ini­tial re­ac­tion is that even if the dos­ing and late stage pro­grams are re­sumed for fi­tusir­an, the com­mer­cial op­por­tu­ni­ty may now be lim­it­ed giv­en the risk-averse na­ture of the he­mo­phil­ia pa­tient pop­u­la­tion (es­pe­cial­ly pa­tients with­out in­hibitors).

The in­ci­dent be­gan when a pa­tient com­plained of ex­er­cise-in­duced hip pain fol­lowed by a se­vere headache. He was di­ag­nosed with a sub­arach­noid he­m­or­rhage on the ba­sis of CT imag­ing and treat­ed with fac­tor VI­II con­cen­trate ad­min­is­tered two to three times dai­ly.

Four­teen days af­ter he was ad­mit­ted to the hos­pi­tal, he died from cere­bral ede­ma. And the cause of death was de­ter­mined to be cere­bral ve­nous si­nus throm­bo­sis, hit­ting a si­nus which drains blood from the brain, not a sub­arach­noid he­m­or­rhage — trig­ger­ing the fear that the clot was trig­gered by the ther­a­py.

The set­back oc­curs just 10 months af­ter Sanofi agreed to pay $100 mil­lion to opt in on the Phase III fi­tusir­an study af­ter part­ner­ing with Al­ny­lam in a $700 mil­lion buy-in back in 2014. Two months ago the part­ners re­port­ed en­cour­ag­ing da­ta from the Phase II tri­al.

Al­ny­lam is no stranger to safe­ty scares and con­cerns about killing pa­tients with its RNAi tech. Last fall the biotech was forced to scrap its sec­ond most ad­vanced drug — re­vusir­an — af­ter re­searchers tracked an im­bal­ance in the num­ber of deaths be­tween the drug arm and the con­trol group. That oc­curred just days af­ter Al­ny­lam took a nasty hit on its stock price af­ter a much ear­li­er-stage drug, the RNAi liv­er dis­ease drug ALN-AAT, was scrapped af­ter three pa­tients ex­pe­ri­enced spik­ing liv­er en­zymes in a Phase I/II.

“We are deeply sad­dened to learn of this pa­tient’s death, and we ex­tend our sym­pa­thies to his fam­i­ly,” said Ak­shay Vaish­naw, ex­ec­u­tive vice pres­i­dent of R&D at Al­ny­lam. “We be­lieve that fi­tusir­an holds great promise as a po­ten­tial treat­ment op­tion for pa­tients with he­mo­phil­ia, and we re­main ful­ly com­mit­ted to its on­go­ing de­vel­op­ment. Fol­low­ing fur­ther in­ves­ti­ga­tion of this safe­ty find­ing, im­ple­men­ta­tion of a risk mit­i­ga­tion strat­e­gy, and align­ment with glob­al reg­u­la­to­ry au­thor­i­ties, we ex­pect to re­sume fi­tusir­an dos­ing in our clin­i­cal stud­ies as soon as pos­si­ble, po­ten­tial­ly as ear­ly as late 2017, with a goal of ad­vanc­ing this in­no­v­a­tive in­ves­ti­ga­tion­al med­i­cine to he­mo­phil­ia pa­tients in need.”

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.

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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.

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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.

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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.

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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.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.