Bio­gen, Ei­sai BACE drug cuts amy­loid be­ta in the brain, but there’s no hard da­ta to show it does any­thing im­por­tant for cog­ni­tion

Just af­ter Mer­ck $MRK re­search raised se­ri­ous doubts about the BACE ap­proach to tack­ling Alzheimer’s dis­ease, re­searchers for Bio­gen $BI­IB and Ei­sai are fight­ing against the tide this week. And they have a long way to go be­fore they start per­suad­ing they may have some­thing of val­ue for pa­tients.

Lynn Kramer

The team fo­cused on the oral BACE drug elen­be­ce­s­tat says the drug is do­ing what it’s in­tend­ed to do, cut­ting down on the amount of amy­loid be­ta in the brains of pa­tients with a mild form of the dis­ease and pro­duc­ing a nu­mer­i­cal de­cline in the rate at which pa­tients’ cog­ni­tion spi­rals down­ward.

But …. the re­searchers were un­able to track any­thing in the 18-month Phase II study that qual­i­fied as a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment on cog­ni­tion scores. Ac­tu­al da­ta were be­ing held back, so we don’t know why ex­act­ly the team con­cludes that the re­sponse sug­gests they may have seen “a de­lay of clin­i­cal symp­tom de­cline in ex­plorato­ry end­points.”

Re­searchers used both the Clin­i­cal De­men­tia Rat­ing Sum of Box­es as well as a new as­sess­ment they’ve been work­ing on.

This wouldn’t be the first time re­searchers tout­ed/hyped a pos­si­ble tie to an im­proved cog­ni­tive score. Eli Lil­ly did it with great suc­cess on the sec­ond piv­otal fail for solanezum­ab, set­ting up a third late-stage study that com­plete­ly failed to show an im­prove­ment in cog­ni­tion or func­tion. Now they’re try­ing it in pre-symp­to­matic pa­tients. And Bio­gen it­self has reg­u­lar­ly stoked hopes for ad­u­canum­ab, its top late-stage drug in the Alzheimer’s field, where noth­ing has worked out in more than a decade.

Sig­nif­i­cant­ly, the re­searchers found no se­ri­ous safe­ty is­sues that could stop the pro­gram at this stage.

The lat­est set­back for Mer­ck al­so un­der­scored fears that the en­tire BACE field is head­ed for the grow­ing scrap heap of drugs — as far as symp­to­matic pa­tients are con­cerned. Mer­ck re­searchers con­clud­ed that their first Phase III tri­al al­so proved that their drug hit its tar­get, with­out sig­nif­i­cant­ly help­ing pa­tients. There have been a num­ber of oth­er BACE fail­ures, but those set­backs have been blamed on the drug’s weak­ness­es, rather than prob­lems with the tar­get.

“It is high­ly en­cour­ag­ing that Study 202 con­firmed elen­be­ce­s­tat’s treat­ment ef­fect in re­duc­ing amy­loid in the brain and sug­gest­ed a slow­ing of clin­i­cal de­cline. Ei­sai and Bio­gen will con­tin­ue to work to­geth­er to ad­vance the on­go­ing Phase III pro­gram (MIS­SION AD) in or­der to con­tribute a new po­ten­tial treat­ment op­tion to Alzheimer’s dis­ease pa­tients as soon as pos­si­ble,” said Lynn Kramer, the CMO for Ei­sai’s Neu­rol­o­gy Busi­ness 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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

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.