Adelene Perkins, Infinity CEO

Could a fourth lead drug fi­nal­ly bring In­fin­i­ty an ap­proval?

Maybe fourth time’s the charm?

In­fin­i­ty Phar­ma­ceu­ti­cals, the thrice-failed on­col­o­gy biotech, an­nounced up­dat­ed da­ta Tues­day from its new lead drug in a pair of can­cers, show­ing that blad­der can­cer pa­tients who took its mol­e­cule in com­bi­na­tion with Bris­tol My­ers Squibb’s Op­di­vo lived near­ly twice as long as pa­tients who took Op­di­vo alone. And the biotech showed the mol­e­cule ap­peared to of­fer a mod­est ben­e­fit for pa­tients with triple-neg­a­tive breast can­cer.

“In our view, these da­ta are over­all pos­i­tive and con­tin­ue to sup­port eganelis­ib po­ten­tial,” Tru­ist’s Robyn Kar­nauskas wrote in a note to in­vestors, us­ing the chem­i­cal name of the drug.

And yet In­fin­i­ty’s stock $IN­FI slid on the news, drop­ping 31% Tues­day from $2.22 to $1.53, al­though it has since bounced back up.

The prob­lem is one In­fin­i­ty has faced be­fore: Whether or not the drug is ef­fec­tive, it may not have a mar­ket. The biotech’s pre­vi­ous lead P13K drug, du­velis­ib, was aban­doned af­ter show­ing a 46% re­sponse rate in non-Hodgkin lym­phoma — good, but not good enough to com­pete in a field where oth­er op­tions are avail­able. (They dumped the drug to Ve­rastem, who got it ap­proved but gen­er­at­ed lit­tle sales). It was the third In­fin­i­ty drug to go down, af­ter clin­i­cal fail­ures for oth­er mol­e­cules in 2009 and 2012 shook what had once been one of the biggest biotechs in tar­get­ed on­col­o­gy.

Sim­i­lar­ly, in­vestors had been hop­ing to see a greater ben­e­fit in triple-neg­a­tive breast can­cer, an in­di­ca­tion that’s no­to­ri­ous­ly tough to treat. In­fin­i­ty showed its drug, when com­bined with Roche’s PD-1 block­er Tecen­triq and chemother­a­py, halt­ed dis­ease for 7.5 months, or just 0.2 months — six days — more than Roche showed Tecen­triq and chemother­a­py can alone.

Those da­ta al­so came out the same day Mer­ck an­nounced Keytru­da im­proved pro­gres­sion-free sur­vival in triple-neg­a­tive breast can­cer, adding an­oth­er op­tion In­fin­i­ty would have to com­pete against.

The da­ta for blad­der can­cer were far stronger, but in­vestors had been hop­ing the com­pa­ny would lay out a clear­er path to ap­proval. In­stead, In­fin­i­ty CEO Ade­lene Perkins promised an up­date to­ward the end of the year and an­a­lysts now ex­pect the tri­al could take longer than an­tic­i­pat­ed. With the FDA tak­ing a tougher stance on PD-1 ap­provals, the com­pa­ny will like­ly have to prove its com­bi­na­tion can im­prove sur­vival in a large study, push­ing ap­proval back to­ward 2025.

In the mean­time, com­peti­tors are en­ter­ing the mar­ket. In­fin­i­ty has stud­ied its drug in pa­tients who have al­ready gone through one line of treat­ment but have yet to re­ceive a check­point in­hibitor. But B. Ri­ley Se­cu­ri­ties’ Kalpit Pa­tel not­ed that PD-1s are in­creas­ing­ly be­ing used in new­ly di­ag­nosed blad­der can­cer pa­tients, in­clud­ing in com­bi­na­tion with Seagen’s new an­ti­body-drug con­ju­gate Pad­cev.

“We ac­knowl­edge a lim­it­ed op­por­tu­ni­ty,” Pa­tel said, es­ti­mat­ing 4,200 pa­tients per year would be el­i­gi­ble for In­fin­i­ty’s drug if it suc­ceeds.

Nev­er­the­less, few an­a­lysts soured on In­fin­i­ty al­to­geth­er, par­tic­u­lar­ly with shares sell­ing at so­da bot­tle prices. Eganelis­ib, a P13K-gam­ma in­hibitor, is in­tend­ed to re­pro­gram the im­mune cells that clus­ter around the tu­mor, short-cir­cuit­ing one of sol­id tu­mors’ key meth­ods for avoid­ing T cells and oth­er tu­mor-killing arms of the im­mune sys­tem.

Ac­cord­ing­ly, the com­pa­ny hoped it would both im­prove re­spons­es in pa­tients who al­ready ex­press PD-L1 and are like­ly to ben­e­fit from check­point ther­a­py, and those who don’t ex­press PD-L1 and are less like­ly to ben­e­fit. In the­o­ry, the mol­e­cule could con­vert some of these tu­mors to PD-L1 pos­i­tive.

An­a­lysts ex­pect In­fin­i­ty to push for an ap­proval in PD-L1-neg­a­tive pa­tients for blad­der can­cer. And some ar­gued that the triple-neg­a­tive breast can­cer da­ta were skewed be­cause In­fin­i­ty had a greater num­ber of neg­a­tive pa­tients than those in Roche’s orig­i­nal tri­al. Bro­ken down by PD-L1 pos­i­tive and neg­a­tive, they not­ed, In­fin­i­ty’s drug ac­tu­al­ly im­proved PFS by 2 months for neg­a­tive pa­tients and near­ly 4 months for pos­i­tive pa­tients.

That kind of spec­u­la­tive analy­sis, though, is far from the kind of ev­i­dence it will take to get ap­proval.

“While en­cour­ag­ing,” Pa­tel wrote, “we cur­rent­ly ex­clude TNBC as a po­ten­tial in­di­ca­tion as we wait for da­ta from ad­di­tion­al num­ber of pa­tients as well as longer-term re­sponse dura­bil­i­ty/PFS re­sults.”

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

David Arthur, Salarius Pharmaceuticals CEO

Salarius Phar­ma­ceu­ti­cals sees with­drawals, 3 of 13 pa­tient re­spon­ders in sar­co­ma tri­al

The Houston-based biotech Salarius Pharmaceuticals is lifting the cover on data from a Phase I/II trial for a drug currently on voluntary hold after a patient death, and the results appear to have underwhelmed investors.

Salarius’ candidate, dubbed seclidemstat, is an oral LSD1 inhibitor that is meant to treat Ewing sarcoma and FET-rearranged sarcomas in patients under 12 years old. The biotech had presented data with 13 patients with “first- and second-relapse Ewing sarcoma” who were treated in combination with topotecan and cyclophosphamide.