Regulatory Decision Summary for Ixchiq

The purpose of this new drug submission (NDS) was to seek market authorization of Ixchiq (a live attenuated vaccine) for active immunization in individuals 18 years and older for the prevention of chikungunya caused by the chikungunya virus (CHIKV), as a single-dose immunization.

After evaluation of the submitted data package, Health Canada authorized Ixchiq for active immunization in individuals 18 years and older for the prevention of disease caused by the chikungunya virus (CHIKV), as a single-dose immunization.

Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV). Symptoms and signs of Chikungunya are most often characterized by sudden onset of high fever, myalgia, arthralgia and pronounced lymphopenia and/or moderate thrombocytopenia, which typically begin 3-7 days after being bitten by an infected Aedes genus mosquito. These changes typically resolve within 7 to 10 days, but up to 40% of patients may suffer from debilitating arthralgia and other symptoms for months to years.

Ixchiq is a live attenuated CHIKV strain.

The data supporting the NDS came from 3 prospective double-blinded clinical studies, to study the immunogenicity and safety of Ixchiq in healthy adults.

The pivotal study compared Ixchiq in 3,093 volunteers and a placebo in 1,035 volunteers after an intramuscular injection. The clinical efficacy of Ixchiq was assessed using the immune response as a surrogate. The seroresponse rate on Day 28 post-vaccination in the study was 98.9% in the Ixchiq group.

Ixchiq was considered safe in adults ≥ 18 years of age, based on assessment data generated from the main study looking at post-vaccination local and systemic reactions in the first 10 days, unsolicited adverse events (AEs) in the first 28 days, AEs of special interest (i.e., Chikungunya-like illness syndrome) in the first 30 days, and serious AEs including deaths in the first 6 months.

Overall, 1,547/3,082 (50.2%) of Ixchiq recipients vs 278/1,033 (26.9%) of placebo recipients experienced at least one solicited systemic adverse reaction. Among Ixchiq recipients, the most common systemic adverse reactions were headache (31.6%), fatigue (28.5%), myalgia (23.9%) and arthralgia (17.2%). Overall, 463/3,082 (15.0%) of Ixchiq recipients vs 115 (11.1%) of placebo recipients experienced at least one injection site adverse reaction. Among Ixchiq recipients, the most common injection site adverse reaction was tenderness (10.6% vs 8.1%). Most injection site reactions resolved within 1 to 5 days. Most systemic adverse reactions (>95%) were mild to moderate and resolved within 2 to 5 days. Overall, 21.8% of Ixchiq recipients reported at least 1 unsolicited AEs compared with 13.3% of placebo recipients with most unsolicited AEs graded as mild or moderate. Unsolicited AEs were significantly more frequently considered related to the vaccination in the Ixchiq arm (9.2% participants) than in the placebo arm (3.7% participants).

Among participants, 361 (11.7%) in the Ixchiq group (n = 3,082) reported chikungunya-like adverse reactions, including 48 participants (1.6%) who reported severe chikungunya-like reactions. Six (0.6%) participants in the placebo group (n = 1,033) reported chikungunya-like adverse events, none of which was severe. The median onset of chikungunya-like adverse events in Ixchiq recipients was 3 days (range 0 to 10 days) after vaccination with a 4 day median duration (range 1 day to at least 6 months). Twenty-two Ixchiq recipients had prolonged chikungunya-like adverse reactions lasting longer than 14 days (median duration 33 days, range 15 days to at least 6 months). Prolonged arthralgia (lasting longer than 14 days) was reported by seven participants.

Overall, there were two serious adverse events requiring hospitalization that were considered to be related to Ixchiq included 1 event of myalgia and 1 event of hypovolemic hyponatremia and atrial fibrillation with both cases fully recovered. There were no serious adverse events reported in the placebo group. Three participants died during Study VLA1553-301 (i.e., coronary artery disease, COVID-19, and anoxic brain injury) with none considered related to Ixchiq. Approximately 0.1% of participants who received Ixchiq versus 0.2% in the placebo group discontinued their trial participation due to adverse reactions. Due to uncertainty regarding the safety of this live attenuated vaccine especially in the third trimester, Ixchiq will be contraindicated in pregnancy.

Based on the currently available immunogenicity and safety evidence, the benefit/risk profile of Ixchiq administered as a single dose to non-pregnant adults ≥ 18 years of age or older is considered favorable.

An updated Risk Management Plan (RMP) for Ixchiq was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Ixchiq has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Ixchiq, not less than 3.0 log10 TCID50/0.5mL, for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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