Regulatory Decision Summary for Twyneo

The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Twyneo (0.1% w/w Tretinoin, 3% w/w Benzoyl Peroxide), filed by Searchlight Pharma Inc.

Upon review of the submitted data package, Health Canada authorized Twyneo (tretinoin and benzoyl peroxide cream) for the topical treatment of acne vulgaris in adults and pediatric patients 9 years of age and older.

The safety and efficacy of Twyneo was evaluated in two multicenter, randomized, double-blind, vehicle-controlled studies which were identical in design (Study 1 and Study 2). The trials were conducted in 858 patients, aged 9 years and older with facial acne vulgaris, who were treated once daily for 12 weeks with either Twyneo or vehicle cream. In both trials, patients were randomized in a 2:1 ratio to receive either Twyneo or vehicle cream. Patients were required to have a score of moderate (3) or severe (4) on the Investigator Global Assessment (IGA), 20 to 100 inflammatory lesions, 30 to 150 non-inflammatory lesions, and two or fewer facial nodules (defined as an inflammatory lesion greater than or equal to 5 mm in diameter). The majority of patients were white (73%) and female (59%). Eighteen (18) (2%) patients were 9 to 11 years of age, 370 (43%) patients were 12 to 17 years of age, and 470 (55%) patients were 18 years of age or older. At baseline, patients had a mean inflammatory lesion count of 30.7 and a mean non-inflammatory lesion count of 46.4. Additionally, 91% of patients had an IGA score of 3 (“moderate”). The co-primary efficacy endpoints were (1) the absolute change from baseline in non-inflammatory and inflammatory lesion count at Week 12, and (2) the proportion of patients with IGA success at Week 12, defined as an IGA score of 0 (“clear”) or 1 (“almost clear”), and at least a two-grade improvement (decrease) from baseline at Week 12. Twyneo was more effective than vehicle cream on the co-primary efficacy endpoints in both trials. In both Study 1 and Study 2, a significantly greater reduction in mean inflammatory lesion counts from baseline was observed in patients treated with Twyneo (reductions of 21.6 and 16.2 inflammatory lesions in the respective studies) compared with those treated with vehicle cream (reductions of 14.8 and 14.1 inflammatory lesions in the respective studies). Similarly, in both Study 1 and Study 2, a significantly greater reduction in mean non-inflammatory lesion counts from baseline was observed in patients treated with Twyneo (reductions of 29.7 and 24.2 non-inflammatory lesions in the respective studies) compared with those treated with vehicle cream (reductions of 19.8 and 17.4 non-inflammatory lesions in the respective studies). In Study 1 and Study 2, respectively, 39.9% and 26.8% of the patients treated with Twyneo achieved an IGA success at Week 12 compared with 14.3% and 15.1% of the patients treated with vehicle cream.

The safety data showed that the most common adverse reactions which occurred in ≥ 1% of patients in Twyneo and with greater frequency than the vehicle cream included application site pain (10.6%), application site dryness (4.9%), application site exfoliation (4.1%), application site erythema (4.0%), application site dermatitis and application site pruritus (1.3% each), and application site irritation (1.1%). Overall, the safety review for Twyneo did not raise specific safety concerns beyond what is known for topical tretinoin and benzoyl peroxide. The safety concerns regarding Twyneo have been addressed through appropriate labelling in the Twyneo Product Monograph.

The Non-clinical studies conducted for this submission found no significant safety concerns. There was mild transient irritation observed in a dermal toxicity study in minipigs treated with tretinoin and benzoyl peroxide. These findings are consistent with the reports of skin irritation in humans. Published literature also supported the safety of benzoyl peroxide and tretinoin. No significant safety concerns were noted.

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

The final labelling and Product Monograph were considered acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Twyneo (tretinoin and benzoyl peroxide cream), 0.1%/3%, for the approved indication of topical treatment of acne vulgaris 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 Twyneo. please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.