Summary of Cancellation for Jyseleca

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.


Product type:

Drug

Medicinal ingredient(s):

filgotinib

Therapeutic area:

Immunosuppressants

Type of submission:

New Drug Submission

Control number:

235219

Decision issued:

No decision was issued by Health Canada. The company cancelled its submission before a final decision was issued.

Date of cancellation:

2021-01-06

What was the purpose of this submission?

This New Drug Submission was filed to seek market authorization for the use of Jyseleca. Jyseleca (filgotinib) is a Janus kinase (JAK) inhibitor proposed as monotherapy, or in combination with conventional synthetic Disease Modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate, for reducing signs and symptoms of moderate to severe Rheumatoid Arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to, one or more DMARDs. The proposed dosing for filgotinib was 200 mg orally once daily (QD), or 100 mg QD in patients with impaired renal function.

What did the company submit to supports its submission?

The company submitted chemistry, bioequivalence, non-clinical, pivotal and non-pivotal clinical trial components, as well as a proposed Product Monograph, draft labels and a Risk Management Plan.

The non-clinical program included a comprehensive set of pharmacology and pharmacokinetic studies, single and multiple dose toxicity studies, assessments of carcinogenicity, genotoxicity and male and female fertility, as well as qualification of impurities.

The submitted clinical package includes data from 27 completed clinical studies: 19 clinical pharmacology studies, a QT study, 5 Phase 2 studies, 3 pivotal Phase 3 studies (FINCH 1, FINCH 2, FINCH 3), and unblinded interim data from an ongoing Phase 3 long-term extension study (FINCH 4).

What was the status of the submission when it was cancelled? What was Health Canada’s assessment of the submission at the time of cancellation?

At the time of the cancellation, the review of the submission was nearing completion and Health Canada was planning to issue a Notice of Non-Compliance (NON), based on clinical and non-clinical issues. The filgotinib nonclinical program had identified significant male reproductive toxicities, which had not been adequately characterized and were considered a possible safety risk in humans.

In the clinical program, the efficacy data demonstrated that while both filgotinib doses (100 mg and 200 mg) could be considered for the RA indication, the proposed 200 mg QD dose did not present a meaningful advantage. The degree of potential incremental benefit from the 200 mg dose was offset by the higher number of serious safety concerns, relative to the filgotinib 100 mg dose.

Health Canada did not consider the safety data provided to be sufficient to support market authorization. At that time, safety clinical studies were ongoing. On December 16, 2020, the clinical division met with the sponsor to discuss the NON issues and the need to complete the ongoing safety studies with filgotinib. The Sponsor chose to withdraw the submission before the NON was issued. These issues were not resolved at the time of cancellation.

What consequences does the cancellation have for patients accessing the drug under the Special Access Programme (SAP), or via clinical trials?

There is no expected impact on SAP and/or clinical trials.

Manufacturer:

Gilead Sciences Canada Inc.

Drug Identification Numbers issued:

N/A

Date filed:

2020-01-16