More JAK inhibitors face delays at FDA

The FDA extended reviews of marketing applications seeking approval of several JAK inhibitors as the regulator continues to scrutinise the safety of the drug class. Pfizer said Wednesday that the target review date of its filing for abrocitinib to treat adults and adolescents with moderate-to-severe atopic dermatitis (AD), as well as an application to expand the label for Xeljanz/Xeljanz XR (tofacitinib) to include adults with active ankylosing spondylitis, has been extended by three months to early in the third quarter. The company provided no further details on either delay.

The FDA, which had granted the abrocitinib application a priority review, was expected to make a decision this month. The filing includes data from the JADE MONO-1 and JADE MONO-2 studies comparing abrocitinib monotherapy with placebo, as well as results from the JADE COMPARE trial of patients who were also on background topical therapy.

Meanwhile, Phase III findings presented at last year's American College of Rheumatology (ACR)/Association of Rheumatology Professionals (ARP) annual meeting showed that Xeljanz met the primary and key secondary endpoint of Assessment in SpondyloArthritis International Society (ASAS) 20 and 40 response, respectively, compared to placebo at week 16. The drug is already approved in the US for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and polyarticular course juvenile idiopathic arthritis, and generated sales of $696 million in the fourth quarter of 2020.

Olumiant decision also postponed

Separately, Eli Lilly and Incyte disclosed that the FDA pushed back a decision for an application seeking approval of Olumiant (baricitinib) for the treatment of adults with moderate-to-severe AD by three months to early in the third quarter. The companies said the delay will give the agency time to review additional data analyses submitted by Eli Lilly in response to recent information requests from the FDA.

The filing is supported by results from the BREEZE development programme, including BREEZE-AD1 and BREEZE-AD2, as well as BREEZE-AD4. Ilya Yuffa, president of Lilly Bio-Medicines, said "we remain confident in [Olumiant] and believe it has the potential to be an effective new treatment option for these patients." The oral drug is already sold in multiple countries, including the US, to treat certain patients with moderately-to-severely active rheumatoid arthritis, and is also cleared in the EU and Japan for adults with moderate-to-severe AD. Eli Lilly reported that Olumiant sales were up 50% in the fourth quarter of 2020 to $192.2 million.

Failed post-marketing safety study for Xeljanz

Last month, AbbVie announced that the FDA was prolonging its review of a marketing application seeking to expand Rinvoq's (upadacitinib) label to include adults with active psoriatic arthritis. The three-month delay means the agency is now expected to decide on the filing for the once-daily oral JAK inhibitor late in the second quarter. 

The extended timelines for the JAK inhibitors come after Pfizer reported results from a post-marketing study earlier this year showing that Xeljanz was associated with higher rates of major adverse cardiovascular events and malignancies versus a TNF inhibitor in patients with rheumatoid arthritis (for more analysis, see KOL Views Q&A: JAK class may be guilty until proven innocent thanks to Xeljanz, says leading rheumatologist). Guggenheim analyst Seamus Fernandez suggested that the review extensions by the FDA could signal that the agency will convene an advisory panel to review safety of the drug class. The analyst noted that while JAK inhibitors have shown good effectiveness in AD at higher doses, he remains sceptical about the safety profile at those levels.

Meanwhile, in December, Gilead Sciences decided it would no longer be looking to obtain US approval for the JAK inhibitor filgotinib after the FDA earlier declined to approve the Galapagos-partnered drug citing concerns over the benefit/risk profile at the 200-mg dose.

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