Regulatory Decision Summary for Vyzulta
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.
Type of submission:
What was the purpose of this submission?
The purpose of this New Drug Submission (NDS) was to seek market authorization of Vyzulta [Latanoprostene bunod ophthalmic solution, 0.024%] for the reduction of intraocular pressure [IOP] in patients with open-angle glaucoma or ocular hypertension.
Why was the decision issued?
The purpose of this New Drug Submission (NDS) was to seek market authorization of Vyzulta [Latanoprostene bunod ophthalmic solution, 0.024%] for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Latanoprostene bunod (LBN), a new chemical entity, consists of the prostaglandin F2α (FP) receptor agonist, latanoprost, linked by an ester group to butanediol mononitrate (BDMN; also referred to as 4-hydroxybutyl nitrate).
In two adequate and well-controlled phase-III trials, non-inferiority of LBN to timolol maleate 0.5% was established for the primary efficacy endpoint of mean IOP in the study eye measured at specified time points: 8 AM, 12 PM, and 4 PM at Week 2, Week 6, and Month 3. In each trial, 420 subjects were randomized in a 2:1 ratio to receive either test drug or Timolol. Both trials had a three-month masked efficacy period. The mean baseline IOP values were comparable between the two treatment groups and both treatment groups demonstrated IOP reductions at each of the nine post-baseline time points in each trial. There was an IOP reduction between 7.5 to 9.0 mmHg in the LBN arms compared to 6.5 to 7.9 mmHg in the Timolol arms. In these studies, diurnal efficacy of LBN was demonstrated in subjects with OAG/OHT across a range of baseline IOPs and also in normotensive healthy eyes upto a period of 12 months. The amount of reduction in IOP was consistent across all relevant subpopulations including age, sex, race/ethnicity, and geographic region. In the Phase 3 Pool, a significantly greater proportion of LBN-treated patients than timolol-treated patients achieved clinically meaningful end points of target IOP of 18 mmHg or lower and at least 25% reduction from baseline. Overall, the pivotal and non-pivotal studies provided substantial evidence of efficacy that is consistent with the currently marketed prostaglandin F2α analogues.
Toxicology studies with LBN in rabbits and rats, suggest that LBN could cause miscarriage, abortion, and fetal harm at clinically relevant doses. Based on the data provided, this risk appears to be higher than that observed for other prostaglandin F2α analogues ophthalmic products. LBN was shown to be abortifacient to pregnant rabbits at exposures ≥0.28 times the clinical dose and teratogenic in rabbits at doses ≥1.4 times the clinical dose. With the exception of the pregnancy risk, the risks for this drug appear to be similar to other prostaglandin F2α analogues currently approved in Canada for the proposed Indication.
A total of 1,335 patients exposed to at least one dose comprised of the safety population. The safety profile of LBN is similar to other marketed topical prostaglandin F2α analogues. In the pivotal trials, the most common ocular adverse reactions observed in patients treated with latanoprostene bunod were: conjunctival hyperemia (6%), eye irritation (5%), and eye pain (4%), and instillation site pain (2%). Labelling of risks typical for the prostaglandin F2α analogs such as iris and periorbital tissue pigmentation, eyelash changes, and macular edema are included in the Product Monograph (PM). There were no notable differences between treatment groups across all study visits for results of clinical laboratory evaluations, vital signs, best-corrected visual acuity, slit lamp examinations, ophthalmoscopy, and cup disc ratio. LBN has not been studied in the pediatric population and pregnant & nursing women. The Risk Management Plan indicated that the risks for using LBN were consistent with the currently marketed prostaglandin F2α analogues.
Overall, LBN demonstrated a tolerable safety profile with no significant systemic effects and the ocular effects were comparable to the two most commonly used classes of IOP-lowering agents, namely prostaglandin F2α analogues (latanoprost) and beta-blocker (timolol).
Overall, Vyzulta [Latanoprostene bunod ophthalmic solution 0.024%] is considered to have a favorable benefit-risk profile for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.