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.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

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Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

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Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.