Image: Atomwise CEO and co-founder Abraham Heifets
FDA approves JAK inhibitors Rinvoq and Cibinqo despite safety concerns
The introduction of Rinvoq and Cibinqo to the atopic dermatitis market will provide more treatment options for many patients.
Dr Judith M. Sills. Credit: Arriello
Dr Eric Caugant. Credit: Arriello
On 14 January, AbbVie and Pfizer received US Food and Drug Administration (FDA) approvals for their Janus kinase (JAK) inhibitors, Rinvoq (upadacitinib) and Cibinqo (abrocitinib), for the treatment of refractory moderate to severe atopic dermatitis (AD). These approvals were based on safety and efficacy data from their respective clinical programmes: Rinvoq’s Measure Up 1,2 (NCT03569293, NCT03607422) and AD Up (NCT03568318), and Cibinqo’s JADE program, which includes JADE-MONO 1,2 (NCT03349060, NCT03575871) and JADE COMPARE (NCT03720470). JAK inhibitors are known for their fast onset of action, but have lately been facing class-wide safety concerns stemming from Pfizer’s post-marketing Oral Surveillance study (NCT02092467). Despite this, their introduction provides more treatment options for moderate to severe AD patients who are overwhelmed with constant itching and scratching, which can seriously deplete patients' quality of life.
The FDA recommends Rinvoq and Cibinqo to be used when all other therapy options are exhausted, including biologics, or when the use of certain therapies is inadvisable, thus placing them behind Sanofi/Regeneron’s Dupixent (dupilumab) and LEO Pharma’s Adbry (tralokinumab), the latter of which received FDA approval last month. The regulator, however, approved all doses for Rinvoq (15mg and 30mg) and Cibinqo (50mg, 100mg and 200mg), dismissing initial fears that only the lower doses would gain approval. Patients will need to be closely monitored as the FDA has given specific guidelines for each dose, titrating up the dosage as needed.
For example, the FDA advises the use of 30mg of Rinvoq in patients who are not responsive to the 15mg dose. The labels are also careful to advise that the drugs should not be used in combination with therapeutic biologics, other JAK inhibitors or potent immunosuppressants, which means they will likely be considered a last line of therapy for treatment-refractory moderate to severe patients.
While Cibinqo’s recommended starting dosage is 100mg, the 50mg dosage was approved for patients with moderate renal impairment, those receiving cytochrome P450 inhibitors and those who are known or suspected to be poor metabolisers of CYP2C19 (an enzyme that breaks down several drug classes), which is determined by genetic variation. Patients who fit these special considerations may increase their dosage to 100mg if they do not respond adequately to 50mg. Pfizer will likely face little competition in these patients since competitors have not targeted these niche populations.
Although both JAK1 inhibitors have been approved for the treatment of refractory moderate-to-severe AD, there are some differences in the labels, as Cibinqo is approved for adults while Rinvoq is available for adults and adolescents (patients aged 12 years and older). Because of this, Rinvoq is expected to have a larger market share due to its anticipated patient reach.
Both AbbVie and Pfizer’s JAK1 assets are the first small molecules and JAK inhibitors to be approved in the US for the treatment of moderate to severe AD ahead of Eli Lilly’s JAK1/2 inhibitor, Olumiant (baricitinib), which is also anticipated to gain FDA approval for adult use soon. Unlike Olumiant’s EU approval, its US approval appears to have straggled behind that of its competitors. Olumiant is likely to become the third oral JAK inhibitor approved in the US. The FDA, however, will likely approve both doses for Olumiant (2mg and 4mg), thereby allowing the JAK1/2 inhibitor to exercise dosing flexibility similar to its competitors.
Although Olumiant’s anticipated approval is likely to target adults only, Eli Lilly has been conducting a Phase III trial, BREEZE-AD-PEDS (NCT03952559), assessing Olumiant in patients aged 2–17 years, which raises the possibility for a label expansion. Similarly, Pfizer has an expanded access protocol (NCT04564755) in place preparing for a label expansion with Cibinqo into the adolescent group (patients aged 12–17 years), which suggests that both companies are looking to expand their footprint, vying for market share currently held by Rinvoq.
These FDA approvals have solidified a future for the JAK inhibitor class in the AD market while also providing hope for patients who are not responding to already available therapies. GlobalData anticipates that their uptake will be slow, but that it may improve with long-term safety and efficacy data.