Re­gen­eron, Sanofi talk up po­ten­tial block­buster fran­chise as Dupix­ent sweeps in rhi­nos­i­nusi­tis PhI­II

A busy clin­i­cal team at Re­gen­eron $REGN and Sanofi $SNY has out­lined an­oth­er seg­ment on the al­ler­gic in­flam­ma­to­ry map that they plan to build their Dupix­ent king­dom up­on.

In two Phase III tri­als, in­ves­ti­ga­tors say, the mega-block­buster hope­ful de­liv­ered a clean sweep over chron­ic rhi­nos­i­nusi­tis with nasal polyps, clear­ing ob­struc­tion and shrink­ing ab­nor­mal tis­sue growth at a much high­er rate than place­bo.

Bri­an Sko­r­ney

The “in­cre­men­tal­ly pos­i­tive” re­sults, as Baird an­a­lyst Bri­an Sko­r­ney puts it, come days ahead of an ex­pect­ed reg­u­la­to­ry de­ci­sion on the mod­er­ate-to-se­vere asth­ma ap­pli­ca­tion, which Sanofi and Re­gen­eron sent in af­ter Dupix­ent hit key end­points in a Phase III a year ago.

While an­a­lysts were more skep­ti­cal of the drug’s com­mer­cial po­ten­tial in asth­ma due to com­pe­ti­tion from both ex­ist­ing (GSK’s Nu­cala) and up­com­ing ri­vals (teze­pelum­ab from As­traZeneca and Am­gen), in this case Sko­r­ney is more in­ter­est­ed in the fact that Dupix­ent beat the cur­rent stan­dard of care — oft-in­ef­fec­tive cor­ti­cos­teroid fol­lowed by ex­pen­sive surgery.

Dupix­ent’s demon­strat­ed abil­i­ty to sig­nif­i­cant­ly re­duce symp­toms in a heav­i­ly pre-treat­ed pa­tient pop­u­la­tion in which more than half of the pa­tients had pre­vi­ous­ly un­der­gone surgery, and near­ly 75% had used cor­ti­cos­teroids, should dri­ve strong com­mer­cial up­take in this in­di­ca­tion where there re­mains a sig­nif­i­cant un­met need.

George Yan­copou­los

SI­NUS-24 and SI­NUS-52 en­rolled 276 and 448 pa­tients, re­spec­tive­ly. At 24 weeks, pa­tients in the two tri­als who re­ceived a com­bo of Dupix­ent and cor­ti­cos­teroid nasal spray ex­pe­ri­enced a 51% and 57% im­prove­ment in nasal con­ges­tion/ob­struc­tion sever­i­ty, ver­sus 15% and 19% in the two place­bo (plus nasal spray) arms. In the drug arms, pa­tients’ nasal polyps score — which mea­sures the size of their polyps — shrunk by an av­er­age of 27% and 33%, while those on place­bo saw 4% to 7% in­creas­es.

Those are the co-pri­ma­ry end­points, with p < 0.0001; the part­ners say Dupix­ent al­so scored on key sec­ondary end­points, from “demon­strat­ing a sig­nif­i­cant re­duc­tion in the need for sys­temic cor­ti­cos­teroids or surgery” to “im­prove­ments in smell and chron­ic rhi­nos­i­nusi­tis symp­toms.”

John Reed

Track­ing a pre-spec­i­fied group of pa­tients who al­so has asth­ma — a com­mon predica­ment among chron­ic rhi­nos­i­nusi­tis suf­fer­ers — re­searchers al­so note an im­prove­ment in lung func­tion and asth­ma con­trol.

“With these da­ta, Dupix­ent has now been shown to ad­dress this in­flam­ma­tion across the com­plete air­way, which man­i­fests in the up­per res­pi­ra­to­ry tract as polyps and con­ges­tion, and in the low­er air­way as asth­ma,” said Re­gen­eron pres­i­dent and CSO George Yan­copou­los, who led the de­vel­op­ment team cred­it­ed for the IL-4/IL13 an­ti­body.

Add that to eczema, where the drug land­ed its first big OK, and it makes three Type 2 or al­ler­gic in­flam­ma­to­ry dis­eases where Dupix­ent has “demon­strat­ed sig­nif­i­cant late-stage ef­fi­ca­cy,” he said in a state­ment.

Ge­of­frey Porges, Leerink

That con­text is key for Ge­of­frey Porges of Leerink, who main­tains that de­spite the strength of the da­ta and the clear po­ten­tial ben­e­fit, “the great­est boost from nasal poly­po­sis will be from in­cre­men­tal share gains in oth­er co-mor­bid atopic/al­ler­gic con­di­tions.” He ex­plains:

Bar­ri­ers to adop­tion in this in­di­ca­tion will be the high cost and con­tin­u­ing bur­den of treat­ment ( ~$36,000/year and bi­week­ly in­jec­tions) and the dif­fer­ent physi­cian pop­u­la­tion (ENT sur­geons) treat­ing polyps, who may not be in­cen­tivized to treat with a bi­o­log­ic agent ver­sus pro­ce­dure. To the ex­tent some of these pa­tients are iden­ti­fied and in the care of al­ler­gists al­ready, they may be more ac­ces­si­ble for Dupix­ent, but sur­geons are like­ly to be slow­er con­vert­ers to in­jectable treat­ment.

“(W)e look for­ward to work­ing with reg­u­la­to­ry au­thor­i­ties around the world to make Dupix­ent an op­tion for peo­ple liv­ing with this chron­ic con­di­tion,” added John Reed, glob­al head of R&D at Sanofi.

Porges es­ti­mates reg­u­la­to­ry fil­ings in 2019 and FDA ap­proval, if it is to come, in 2020.

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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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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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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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. 

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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.