Giovanni Caforio, Bristol Myers Squibb CEO (Pablo Martinez Monsivais/AP Images)
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.
While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.
Tillman Gerngross (Adagio)
Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.
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In the same way that the FDA signs off on flu vaccines every year without requiring large clinical trials to measure their efficacy, the FDA may employ a similar strategy in authorizing variant-focused versions of the mRNA vaccines.
As the world braces for more data on the latest variant Omicron, which may reduce vaccine efficacy, top vaccine developers like Moderna and Pfizer-BioNTech have promised they can pull together a new vaccine targeted against a specific Covid variant in about 100 days. Since Omicron emerged last week, Pfizer-BioNTech, Moderna and J&J have all said they’ve begun work on Omicron-specific vaccines, if needed.
Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.
Shares of Fennec Pharmaceuticals stock were cut almost in half early Monday as the company said manufacturing issues caused another FDA rejection of its reformulated version of sodium thiosulfate, which is intended to help kids who lose hearing due to chemo treatment.
The biotech had resubmitted an NDA for the drug to treat platinum-based, chemo-related ototoxicity in young children earlier this year. The first NDA was denied by the FDA last year, with the agency citing manufacturing issues with the biotech’s supplier.
Dutch VC Forbion is hopping on the ever-lengthening SPAC train.
To be led by Jasper Bos, who joined Forbion Growth as a general partner back in May just after the fund closed at $428 million, Forbion European Acquisition will target late-stage opportunities in the life sciences industry in Europe to merge with and bring onto Nasdaq.
Cyril Lesser, senior controller at Forbion, will be the CFO while Bos serves as CEO.
Jeff Albers, Blueprint Medicines CEO
J&J’s Rybrevant scored the first approval back in May for a small group of lung cancer patients with a rare EGFR mutation. Despite a swarm of other biopharma companies angling for a piece of that market, Blueprint Medicines is betting nearly $500 million on a candidate it thinks will stand out.
Blueprint is putting down $250 million in cash and another $215 million in biobucks for Lengo Therapeutics and its preclinical non-small cell lung cancer program LNG-451. Though it hasn’t been tested in humans, Blueprint says the candidate was ‘highly brain-penetrant’ in preclinical trials, and has the potential to inhibit all common EGFR exon 20 insertion variants — which are found in just 2% to 3% of NSCLC patients.
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Amid burgeoning efforts to create a new type of cell therapy out of regulatory T cells — whether by channeling or blocking their immunosuppressive power — Quell Therapeutics wants to shoot for a first.
If everything goes well, the Syncona-backed biotech will be in the clinic early next year, marking what it calls the historic feat of dosing a patient with a CAR-Treg with multiple edited genes.
Rogerio Vivaldi, Sigilon CEO (Sigilon via website)
Back in July, the FDA placed a clinical hold on the Bob Langer and Flagship-backed biotech Sigilon Therapeutics for its lead program to treat hemophilia A. On Monday, Sigilon reported what caused the pause.
After a patient in the three-person Phase I/II study reported a serious adverse event, Sigilon discovered the spheres used to deliver the cell therapy had fibrosed, the biotech announced Monday. As a result, the treatment contained within the spheres was no longer viable after the patient developed inhibitors to Factor VIII.
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https://endpts.com/amid-jak-debacle-bristol-myers-settles-in-for-fdas-long-review-of-potential-first-tyk2-drug/
