There are 2,004 can­cer im­munother­a­pies crowd­ing in­to the pipeline. Now what?

Here’s a sim­ple set of facts with some com­plex im­pli­ca­tions.

There were 469 new PD-1/L1 can­cer check­point stud­ies launched this year, which re­quire 52,000 pa­tients to ful­ly en­roll all of them.

On the one hand, re­searchers for the non­prof­it Can­cer Re­search In­sti­tute say, that sen­tence un­der­scores the boom in im­munother­a­py that’s been trans­form­ing can­cer treat­ment around the world.

But there’s more.

The ex­plo­sion of pre­clin­i­cal and clin­i­cal-stage pro­grams that has erupt­ed in im­munother­a­pies is rais­ing se­ri­ous ques­tions about the in­trin­sic val­ue of each hu­man study be­ing mount­ed for more than 2,000 I/O agents now in de­vel­op­ment. Is there a more ef­fi­cient way to man­age stud­ies, to get the max­i­mum im­pact from every new tri­al? Can you jus­ti­fy all these tri­als, par­tic­u­lar­ly small, sin­gle-site ef­forts?

Be­fore rais­ing the is­sue, the CRI — which spe­cial­izes in im­munother­a­pies — want­ed to present a clear pic­ture of the scene to every­one in the field.

By as­sign­ing two tu­mor im­mu­nol­o­gists to comb through a va­ri­ety of glob­al tri­al data­bas­es over a year’s time, Aiman Sha­l­abi — CRI’s chief med­ical of­fi­cer and di­rec­tor of the An­na-Maria Kellen Clin­i­cal Ac­cel­er­a­tor — be­lieves that they have, for the first time, es­tab­lished a bird’s eye view of the en­tire im­munother­a­py land­scape span­ning the plan­et, from Shang­hai to Boston. Sha­l­abi jour­neyed to Gene­va to share the re­sults this week­end with the Eu­ro­pean So­ci­ety of Med­ical On­col­o­gy IO meet­ing in Gene­va.

It is stag­ger­ing in scope.

“It’s nev­er been seen be­fore in the drug de­vel­op­ment space or the can­cer space,” says Sha­l­abi, and it’s re­shap­ing can­cer R&D in ways that de­mand some new ap­proach­es to de­vel­op­ment. “It’s time to stop putting new sci­ence on top of the old in­fra­struc­ture and do things dif­fer­ent­ly.”

Do­ing that is go­ing to re­ly on more col­lab­o­ra­tive ef­forts in the in­dus­try and acad­e­mia, and he is spear­head­ing a move to do more of that at the CRI af­ter rais­ing the sub­ject in can­cer R&D cir­cles.

Among the high­lights of the CRI re­port:

— There are 2,004 im­munother­a­py agents in de­vel­op­ment.

— 940 of these I/O ther­a­pies are in clin­i­cal-stage de­vel­op­ment, with 1,064 in the pre­clin­i­cal stage.

— There are 164 PD-1/L1 agents in de­vel­op­ment, with 50 in the clin­ic and 5 on the mar­ket. They have in­spired 1,502 tri­als with 1,105 com­bos.

— 344 are can­cer vac­cines in hu­man stud­ies, and 224 are clin­i­cal-stage cell ther­a­pies.

— There are 69 on­colyt­ic virus­es in clin­i­cal de­vel­op­ment, all in the sec­ond wave be­hind Am­gen’s T-Vec; 95 are pre­clin­i­cal.

— There are 99 T cell tar­get­ed im­munomod­u­la­tors in clin­i­cal de­vel­op­ment, 199 in pre­clin­i­cal de­vel­op­ment.

— There are 165 dif­fer­ent tar­gets be­ing com­bined in check­point stud­ies, with 251 in­clud­ing an an­ti-CT­LA-4 and 170 in­volv­ing chemother­a­pies.

— 0f 1,105 PD-1/L1 drug stud­ies CRI ex­am­ined, 60% are small­er, non-in­dus­try sup­port­ed tri­als.

That last point in par­tic­u­lar at­tract­ed Sha­l­abi’s at­ten­tion. These small­er stud­ies of­ten in­volve aca­d­e­m­ic re­searchers in sin­gle-site tri­als, re­ly­ing on mod­est sup­port from the man­u­fac­tur­er. At a time that each new study in the re­cent wave in­volves dwin­dling num­bers of pa­tients, Sha­l­abi sees two un­der­ly­ing trends: The abil­i­ty to track a ben­e­fit with small­er pa­tient groups, and these sin­gle-site af­fairs that are like­ly to de­liv­er da­ta that will be hard­er to in­ter­pret.

Says Sha­l­abi: “It’s go­ing to be a big chal­lenge to re­cruit and then in­ter­pret them.”

“More and more of these stud­ies are just be­ing de­signed lo­cal­ly; there’s an ap­pear­ance of over­crowd­ing,” he says. “I won­der if these small stud­ies are go­ing to make a con­tri­bu­tion.”

Sha­l­abi be­lieves the da­ta un­der­score the need for more col­lab­o­ra­tions, a greater em­pha­sis on mul­ti-site stud­ies with a more care­ful use of um­brel­la tri­al plat­forms to find faster and more ef­fi­cient means of putting I/O agents through hu­man stud­ies.

There’s one oth­er thing that Sha­l­abi doesn’t doubt.

“What we’ve found is just an un­be­liev­able amount of in­no­va­tion out there,” he says. And it is hav­ing a re­al im­pact on the stan­dard of care in can­cer.

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.

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.

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.