The stel­lar an­ti­body shop at Re­gen­eron wins a ‘break­through’ tag for its next big PhI­II drug

Richard Dun­bar

Re­gen­eron $REGN has one of the best track records in the busi­ness when it comes to build­ing amaz­ing­ly ef­fec­tive an­ti­bod­ies. It did it with Dupix­ent for eczema and Pralu­ent for cho­les­terol. And now one of its Phase II stars just earned a break­through tag from the FDA, which puts it on the in­side track at the agency as it goes in­to piv­otal stud­ies for slash­ing triglyc­eride.

The drug is evinacum­ab. The tar­get is once again ex­tra­or­di­nar­i­ly high lev­els of LDL cho­les­terol. But the tar­get is dif­fer­ent. This an­ti­body tack­les an­giopoi­etin-like pro­tein 3, or ANGPTL3. ANGPTL3 in­hibits lipopro­tein li­pase and en­dothe­lial li­pase, play­ing a key role in lipopro­tein me­tab­o­lism.

Re­searchers are test­ing the drug in hy­per­c­ho­les­terolemia in pa­tients with rare cas­es of Ho­mozy­gous Fa­mil­ial Hy­per­c­ho­les­terolemia (HoFH). And it could fit com­fort­ably in their port­fo­lio, right next to Pralu­ent.

The FDA cit­ed da­ta from a small Phase II study for the drug in hand­ing out the BTD, which is de­signed to open doors to de­vel­op­ers as they ad­vance sig­nif­i­cant new drugs with high po­ten­tial through the clin­ic. In the Phase II in­ves­ti­ga­tors mon­i­tored triglyc­eride lev­els for at least five months fol­low­ing an in­jec­tion. Six dos­es were test­ed and in the top three dose-groups, triglyc­erides were cut by 64% to 73%. At the time, Penn’s Richard Dun­bar not­ed two dis­tinct ad­van­tages in man­ag­ing triglyc­erides: re­duc­ing hos­pi­tal­iza­tion for pan­cre­ati­tis pa­tients and re­duc­ing the risk of heart dis­ease.

“Cur­rent med­ica­tions such as fi­brates or pre­scrip­tion fish oils ef­fec­tive­ly low­er triglyc­erides, but leave much to be de­sired, each on­ly low­er­ing lev­els by 20 to 50 per­cent,” Dun­bar said at the time. “Val­i­dat­ing a drug that low­ers triglyc­erides well be­yond that range would un­doubt­ed­ly take us to the next lev­el, par­tic­u­lar­ly since it could be com­bined with cur­rent oral med­ica­tions for those pa­tients with ex­tra­or­di­nar­i­ly high triglyc­erides who of­ten can’t achieve safe lev­els with our usu­al med­ica­tions. A sim­i­lar ap­proach has been tak­en for low­er­ing cer­tain cho­les­terol with the ad­vent of PC­SK9 in­hibitors, which uti­lize a sim­i­lar mon­o­clon­al an­ti­body mech­a­nism.”

Prov­ing that and win­ning cov­er­age from pay­ers won’t be easy, as Re­gen­eron and its close part­ner Sanofi are well aware af­ter their Pralu­ent ex­pe­ri­ence. And Sanofi — which shoul­ders much of the Phase III load on its part­nered ther­a­pies — al­ready opt­ed out of this an­ti­body. But Re­gen­eron seems ready to push this drug in­to their whol­ly-owned late-stage pipeline, tear­ing off an­oth­er ma­jor Phase III ef­fort for a re­mark­ably ef­fec­tive R&D group.

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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Deborah Dunsire. Lundbeck

Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation for a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month.

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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.