Giovanni Caforio, Bristol Myers Squibb CEO (Pablo Martinez Monsivais/AP Images)

Amid JAK de­ba­cle, Bris­tol My­ers set­tles in for FDA's long re­view of po­ten­tial first TYK2 drug

Bris­tol My­ers Squibb has $4 bil­lion hopes for its late-stage TYK2 in­hibitor deu­cravac­i­tinib, but the FDA’s re­cent neg­a­tive re­view for the JAK in­hibitor class has damp­ened hopes some­what. Now, the agency will get its first good look at TYK2, and Bris­tol My­ers will have to wait and hold its breath.

The FDA has set a tar­get re­view date of Sept. 10, 2022, for deu­cravac­i­tinib, a po­ten­tial first-in-class oral in­hibitor for the TYK2 sig­nal­ing path­way in pso­ri­a­sis that would be a chal­lenger to the con­tro­ver­sial JAK in­hibitors, the drug­mak­er said Mon­day.

The agency will base its re­view on find­ings from the Phase III PO­E­T­YK-PSO pro­gram, which test­ed deu­cravac­i­tinib in a three-way head-to-head against Am­gen’s Ote­zla and place­bo in mod­er­ate-to-se­vere plaque pso­ri­a­sis.

In terms of PASI 75, a mea­sure of dis­ease sever­i­ty, 58.7% and 53.6% of pa­tients on deu­cravac­i­tinib achieved PASI 75 re­sponse re­spec­tive­ly, in the PO­E­T­YK-PSO-1 and PO­E­T­YK-PSO-2 stud­ies, Bris­tol My­ers said in April. Mean­while, just 12.7% and 9.4% of place­bo pa­tients and 35.1% and 40.2% of pa­tients on Ote­zla achieved the same.

Even more promis­ing for Bris­tol My­ers, deu­cravac­i­tinib main­tained its edge over Ote­zla be­tween 24 and 52 weeks of treat­ment. At the six-month check-in, 69.0% and 59.3% of pa­tients on deu­cravac­i­tinib hit PASI 75 ver­sus 38.1% and 37.8% on Ote­zla. Of those deu­cravac­i­tinib pa­tients who hit the PASI 75 mark at six months, 82.5% and 81.4% main­tained that re­sponse at the one-year check in.

Deu­cravac­i­tinib showed sim­i­lar­ly high­er rates of skin clear­ance than place­bo and Ote­zla with a slight­ly high­er rate of se­vere side ef­fects than Am­gen’s drug.

Those side ef­fects will be a key point of con­tention dur­ing the FDA’s re­view, giv­en the TYK2 path­way is part of the JAK fam­i­ly. Bris­tol My­ers says deu­cravac­i­tinib’s high de­gree of se­lec­tiv­i­ty means the drug doesn’t in­hib­it JAK1, JAK2 or JAK3, which could help the drug avoid some of that class’ se­vere side ef­fects.

In Sep­tem­ber, the FDA wrapped a post­mar­ket­ing safe­ty re­view for Pfiz­er’s Xel­janz, find­ing an in­creased risk of se­ri­ous heart-re­lat­ed events such as heart at­tack or stroke, can­cer, blood clots, and death. That un­wel­come up­date took a big hit out of not on­ly Pfiz­er but the JAK class on the whole — in­clud­ing block­buster hope­fuls like Ab­b­Vie’s Rin­voq — af­ter the FDA changed the class’ la­bel to lim­it use to cer­tain pa­tients who are not treat­ed ef­fec­tive­ly or who ex­pe­ri­ence se­vere side ef­fects with the TNF block­ers.

While deu­cravac­i­tinib’s chances ap­pear good in pso­ri­a­sis, break­ing out in­to oth­er in­di­ca­tions could prove a chal­lenge giv­en some less-than-stel­lar re­sults else­where. In Oc­to­ber, deu­cravac­i­tinib flopped a key Phase II test in ul­cer­a­tive col­i­tis, fail­ing to spur clin­i­cal re­mis­sion at three months and miss­ing key sec­ondary end­points at an in­ter­im check-in.

De­tails on the fail­ure were slim, but Bris­tol My­ers is still hold­ing out hope in this in­di­ca­tion with an­oth­er Phase II test in the works and a broad clin­i­cal pro­gram un­der­way.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Teresa Graham, incoming Roche Pharmaceuticals CEO

In­com­ing Roche CEO builds out his top team, tap­ping Genen­tech vet to lead phar­ma di­vi­sion

Roche announced another leadership shuffle Thursday morning – the head of global product strategy, Teresa Graham, will take over as CEO of Roche Pharmaceuticals in March while the company’s corporate executive committee will make a spot for Levi Garraway, CMO and executive VP of global product development.

Thomas Schinecker will take over the top spot as Roche group CEO in March, leaving his spot as head of diagnostics.

FDA ap­proves GSK's ane­mia drug with safe­ty warn­ing — af­ter bat­ting back sim­i­lar drugs

GSK has secured the first of four US approvals it’s hoping for this year, as the FDA greenlit daprodustat as a treatment for anemia due to chronic kidney disease.

But the FDA limited the use of the drug, to be marketed as Jesduvroq, to patients who have been receiving dialysis for at least four months and stopped short of approving it for patients not dependent on dialysis — in line with the recommendations of the advisory committee it consulted.

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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Te­va drops out of in­dus­try trade group PhRMA

Following in AbbVie’s footsteps, Teva confirmed on Friday that it’s dropping out of the industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA).

Teva didn’t give a reason for its decision to leave, saying only in a statement to Endpoints News that it annually reviews “effectiveness and value of engagements, consultants and memberships to ensure our investments are properly seated.”

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Sanofi CFO Jean-Baptiste de Chatillon (L) and CEO Paul Hudson (Romuald Meigneux/Sipa via AP Images)

Sanofi sees downtick in flu sales as it preps for launch of RSV an­ti­body

Sanofi expects its RSV antibody jointly developed with AstraZeneca will be available next season, executive VP of vaccines Thomas Triomphe announced on the company’s quarterly call.

Beyfortus, also known as nirsevimab, was approved in the EU back in November and is currently under FDA review with an expected decision coming in the third quarter of this year. The news comes as the FDA plans to hold advisory committee meetings over the next couple months to review RSV vaccines from Pfizer and GSK.