Up­dat­ed: In sur­prise turn, FDA ad­comm votes in fa­vor of Arde­lyx CKD drug de­spite agency ques­tions

Af­ter the FDA re­ject­ed and ques­tioned Arde­lyx’s po­ten­tial drug for the con­trol of serum phos­pho­rus lev­els in adults with chron­ic kid­ney dis­ease on dial­y­sis, the FDA’s Car­dio­vas­cu­lar and Re­nal Drugs ad­vi­so­ry com­mit­tee on Wednes­day vot­ed 9-4 in fa­vor of the drug as a monother­a­py, and 10-2 (with one ab­sten­tion) in fa­vor of the drug when ad­min­is­tered in com­bo with phos­phate binder treat­ment.

Ad­comm com­mit­tee chair Ju­lia Lewis of Van­der­bilt Med­ical Cen­ter said the drug, known as tena­panor, of­fers small­er pills, and al­though it may see less ef­fi­ca­cy than the cur­rent stan­dard of care, there’s a small sub­set of CKD pa­tients who will re­spond to monother­a­py and “let’s make that avail­able to them.”

Pan­elist Ed­ward Kasper, pro­fes­sor in car­di­ol­o­gy at Johns Hop­kins, al­so vot­ed in fa­vor of it as a monother­a­py, call­ing the safe­ty ques­tions around se­vere di­ar­rhea ac­cept­able giv­en how close­ly this pop­u­la­tion will be mon­i­tored, and he said there’s clear­ly a role for this drug. Oth­ers who vot­ed against tena­panor as a monother­a­py raised ques­tions about the mag­ni­tude of the ef­fect of the drug.

In af­ter-hours trad­ing yes­ter­day evening, Arde­lyx’s stock price rose by as much as 75%. The FDA’s Of­fice of New Drugs is ex­pect­ed to pro­vide a re­sponse to Arde­lyx’s ap­peal to its ear­li­er CRL with­in 30 days, the com­pa­ny said.

“To­day’s vote by the CR­DAC is a promis­ing de­vel­op­ment for the chron­ic kid­ney dis­ease com­mu­ni­ty, as pa­tients con­tin­ue to strug­gle to con­trol serum phos­pho­rus lev­els de­spite use of cur­rent­ly avail­able ther­a­pies, which are all lim­it­ed to the phos­phate binder class,” Mike Raab, pres­i­dent and CEO of Arde­lyx, said in a state­ment. “We are con­fi­dent that the da­ta from three Phase 3 clin­i­cal tri­als in­volv­ing more than 1,200 pa­tients sup­port the ap­proval of XPHOZAH in the U.S. for the con­trol of serum phos­pho­rus in adult pa­tients with CKD on dial­y­sis.”

De­bate dur­ing the morn­ing Wednes­day cen­tered on FDA’s ques­tions around the mag­ni­tude of ben­e­fit of the drug in the piv­otal tri­als.

But Arde­lyx made the case that tena­panor, which is al­ready ap­proved for ir­ri­ta­ble bow­el syn­drome with con­sti­pa­tion in adults, can help what is a sig­nif­i­cant un­met need for new op­tions to con­trol serum phos­pho­rus lev­els. Even the FDA’s ini­tial re­jec­tion let­ter in 2021 said that the sub­mit­ted da­ta “pro­vide sub­stan­tial ev­i­dence that tena­panor is ef­fec­tive in re­duc­ing serum phos­pho­rus in CKD pa­tients on dial­y­sis,” Arde­lyx’s pre­sen­ta­tion said.

FDA, how­ev­er, point­ed to a mean treat­ment ef­fect for tena­panor in this pop­u­la­tion of −0.7 mg/dL in both monother­a­py stud­ies, which “ap­peared to be less than that ob­served with ap­proved agents (~1.5 to 2.2 mg/dL).” And for tena­panor use in com­bi­na­tion with phos­phate binder treat­ment, the FDA said the mag­ni­tude of the treat­ment ef­fect was sim­i­lar to that ob­served in the monother­a­py tri­als.

Even still, in the com­mit­tee’s dis­cus­sion, pan­elists re­it­er­at­ed that there would be a sub­set of pa­tients who will ben­e­fit from Arde­lyx’s pill, par­tic­u­lar­ly those who can’t tol­er­ate phos­phate binders that are large and dif­fi­cult to swal­low (al­though pill bur­den wasn’t tab­u­lat­ed) and have to be tak­en mid-meal, ac­cord­ing to some of the pub­lic com­ments.

Ad­comm pan­elist Su­san Mend­ley of the NIH’s Di­vi­sion of Kid­ney, Uro­log­ic and Hema­to­log­ic Dis­eases, who vot­ed in fa­vor of tena­panor as monother­a­py, not­ed that while oral phos­phate binders have shown a larg­er ef­fect size, many pa­tients don’t tol­er­ate them, and they’re not pleas­ant to take. As a monother­a­py in the right pa­tient, “I think they have met their out­come,” she said.

But pan­elist Christo­pher O’Con­nor of Vir­ginia’s In­o­va Heart and Vas­cu­lar In­sti­tute, who vot­ed against tena­panor, ques­tioned whether 0.7 mg/dL “is enough when you’re talk­ing about a sur­ro­gate end­point that has not been val­i­dat­ed. We have to talk about the clin­i­cal mean­ing­ful­ness we have, and I’m con­cerned it may not be there.” FDA brief­ing doc­u­ments raised sim­i­lar ques­tions about the mag­ni­tude of the treat­ment ef­fect.

Ad­comm mem­ber Lin­da Fried of the Uni­ver­si­ty of Pitts­burgh, who vot­ed in fa­vor of the drug’s risk-ben­e­fit pro­file, said she doesn’t see tena­panor much as a monother­a­py ex­cept in those who don’t tol­er­ate the phos­phate binders.

Safe­ty con­cerns from FDA honed in on both­er­some and some­times se­vere di­ar­rhea, with the ma­jor­i­ty of cas­es last­ing more than 30 days, and with se­vere mean­ing the tri­al par­tic­i­pant was un­able to work or con­duct usu­al ac­tiv­i­ties. Al­most half of the tena­panor arm in one of the piv­otal tri­als re­quired a change of dose or dis­con­tin­ued be­cause of di­ar­rhea, FDA’s safe­ty an­a­lyst Se­le­na De­Con­ti told the com­mit­tee.

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with com­ment from Arde­lyx and the change in stock price.

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.

Thomas Gad, Y-mAbs Therapeutics founder and interim CEO

FDA re­jects Y-mAbs’ neu­rob­las­toma drug af­ter tak­ing is­sue with clin­i­cal tri­al de­sign

Uncertainty about clinical trial evidence has led the FDA to hand down a complete response letter for Y-mAbs’ neuroblastoma drug, casting a cloud on the future of a candidate that had gone through a long development journey in a rare pediatric cancer.

Y-mAbs said it’s disappointed “but not surprised” given that the agency’s oncology drug advisory committee had voted 16-0 against its drug’s approval a few weeks ago.

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Raul Rodriguez, Rigel Pharma CEO

Rigel Phar­ma scores FDA ap­proval for leukemia, kick­ing off show­down with Servi­er in IDH1

When Rigel Pharma bought olutasidenib from Forma Therapeutics, it acquired a drug that already secured a PDUFA date at the FDA — for February 2023. But regulators are ready to give their OK sooner than that.

The FDA has approved the IDH1 inhibitor as a treatment for adult patients with relapsed or refractory acute myeloid leukemia who have a susceptible IDH-1 (isocitrate dehydrogenase-1) mutation as detected by an FDA-greenlit test. Rigel will market it as Rezlidhia.

Tim Pearson, Carrick Therapeutics CEO

Pfiz­er backs $60M in­fu­sion in­to Car­rick, teams up on breast can­cer treat­ment

In a big week for Carrick Therapeutics, the company announced $60 million in funding for its lead breast cancer drug and development of a second program, as well as a collaboration with Pfizer for combo development.

The $35 million from Pfizer comes with an agreement under which Pfizer will support Carrick’s Phase II study of samuraciclib in combination with Pfizer’s Faslodex for advanced breast cancer. Along with the investment, Adam Schayowitz, vice president and development head of breast cancer, colorectal cancer and melanoma at Pfizer global product development, will join Carrick’s scientific advisory board.

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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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Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

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Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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