Regulatory Decision Summary for Olumiant

This Supplemental New Drug Submission (SNDS) Clinical/ Chemistry and Manufacturing was filed to obtain market authorization for a new indication for Olumiant for the treatment of adult patients with severe alopecia areata. Additionally, in support of this new indication, this SNDS includes Chemistry and Manufacturing information to support a new 4 mg strength tablet of Olumiant.

The proposed indication was supported by the results of two pivotal studies: the Phase 2/3 JAHO study and the Phase 3 JAIR study. These were multicenter, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and safety of Olumiant in adults with severe alopecia areata who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT). In the Phase 3 portion of JAHO study and the JAIR study, 654 and 546 patients, respectively, were randomized at a 2:2:3 ratio to placebo, Olumiant 2 mg once daily (QD), or Olumiant 4 mg QD for 36 weeks.

The primary efficacy endpoint in both studies was the proportion of patients who achieved at least 80% scalp hair coverage (SALT ≤20) at Week 36. The primary efficacy endpoint was achieved with Olumiant 2 mg and Olumiant 4 mg in both the JAHO study and JAIR study: at Week 36, the rate of responders with SALT ≤20 was statistically significantly higher in Olumiant 4 mg (35.2% in JAHO study and 32.5% in JAIR study) and Olumiant 2 mg (21.7% in JAHO study and 17.3% in JAIR study) as compared to placebo (5.3% in JAHO and 2.6% in JAIR). The magnitude of effect was consistent across studies and clinically significant with a clear dose-response effect. A statistically significant response versus placebo could be achieved with Olumiant 4 mg as early as Week 16 in JAHO and Week 24 in JAIR. The efficacy of Olumiant 4 mg was further supported by all ten key multiplicity-controlled secondary endpoints in JAHO study and seven in JAIR study, including the proportion of patients who achieved at least 90% scalp hair coverage (SALT ≤10), Patient Reported Outcome for scalp hair improvement, Clinical Reported Outcome (ClinRO) for improvement of eyebrow hair loss, and ClinRO for improvement of eyelash hair loss. Olumiant 2 mg achieved seven key secondary endpoints in JAHO study and one in JAIR study. The 2 mg dose failed to achieve consistent improvement in eyelash and eyebrow hair loss. Therefore, Olumiant 4 mg QD was considered the best dosing regimen to treat patients with eyebrow or eyelash involvement. Additionally, subgroup analyses demonstrated that Olumiant 4 mg was able to elicit a clinically relevant rate of responders in patients with very severe AA (SALT ≥95) that was not observed with the 2 mg dose. Therefore, Olumiant 4 mg QD was considered the best dosing regimen to treat patients with very severe AA (SALT ≥95).

In general, the safety data was consistent with the known safety profile of Olumiant, which was already described for the previous approved indication of rheumatoid arthritis. In the placebo-controlled pivotal trials, 365 and 540 patients were exposed to Olumiant 2 mg QD and 4 mg QD, respectively, for 36 weeks. No deaths were reported, and adverse reactions (ARs) tended to be reported slightly more frequently with Olumiant (41% to 44%) compared to placebo (31%). The most frequent ARs were infections, acne, folliculitis, hyperlipidemia, and creatine phosphokinase (CPK) increase. These are known and labelled potential adverse effects of Olumiant. Most Adverse Events (AEs) were mild to moderate in intensity, as only 2-4% were considered severe. Approximately 3% of participants discontinued treatment due to AEs.

Baricitinib is a Janus kinase (JAK) inhibitor. Adverse event of special interest associated with JAK inhibitors were observed in the clinical program, including serious infections , hyperlipidemia, increased creatine phosphokinase (CPK), neutropenia, and thrombocytosis. The safety data at week 52 was consistent with that from week 36 with a small increase in rates of AEs and serious AEs. The increase was more pronounced with the 4 mg dose compared to the 2 mg dose. A contraindication in pregnant women was added due to very small non-clinical safety margins for reproductive and developmental adverse outcomes, and some dosing recommendations were adjusted to reflect pharmacokinetics findings in patients with moderate renal impairment or when strong OAT3 inhibitors are used concomitantly.

Overall, the anticipated benefit of Olumiant in the treatment of adult patients with severe alopecia areata is expected to outweigh the risks under the conditions of use recommended in the Olumiant Product Monograph at this time and with post-market requirements outlined in the Risk Management Plan.

For further details about Olumiant, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.