The evaluator recommends approval of authorisation of bimatoprost ophthalmic solution 0.03% in the treatment of eyelash hypotrichosis subject to:
Satisfactory responses to questions (see below).
Adoption of changes suggested for the product information and CMI.
The alteration of the indication to include a statement that the product is only to be used in adults and in those patient groups in which it has been studied (idiopathic and post-chemotherapy).
It was claimed in the clinical dossier that the applicator used to apply Latisse to the eyelid margin delivers a fraction of one drop. The evaluator could not locate data to confirm this. Can the sponsor provide evidence that the dosage of Latisse delivered by the applicator is less than one drop? And explain if patients can apply more than one drop to the applicator.
The clinical development program included in the dossier includes relatively few Asian subjects. Discuss available efficacy data for Asian subjects and whether specific efficacy information relating to the Asian racial group should be included in the product information.
In Study 192024-039 there was a notably high response rate on the primary efficacy outcome in African American subjects receiving vehicle (48.8%). The comparative rate in the vehicle group in study 192024-032 was 18.4%. Explain the reasons for this finding.
Present and discuss rates of mild, moderate and severe AEs in the three main efficacy/safety studies (192024-032, 038 and 039). Include rates for all AEs together with a breakdown by SOC for the overall, idiopathic and post chemotherapy populations.
The clinical development program included in the dossier includes relatively few Asian subjects. In addition it was noted that African Americans had a slightly different safety profile with a higher rate of skin pigmentation which suggests there may be varying safety findings in different racial groups. What safety data are available in Asian subjects? Discuss these findings. Discuss also whether specific safety information relating to the Asian racial group should be included in the PI.
The rate of SAEs was notably higher in the post chemotherapy group treated with bimatoprost (13.3% versus 6.1%) compared to the idiopathic group (2.7% versus 1.2%). While it was explained that there were no eye-related SAEs nor treatment-related SAEs in post chemotherapy patients, this finding needs further explanation. Discuss the implication of the sample size on the finding.
Second round evaluation of clinical data submitted in response to questions
Two studies were conducted evaluating this issue. In the first, 36 subjects applied one drop of Latisse vehicle to the applicator and then applied the vehicle on the eyelid margin. The applicator was weighed before and after application. The mean (standard deviation (SD)) amount of solution applied was 2.1 (1.19) µL. The standard volume of an eye drop expelled from the Latisse bottle was reported at approximately 30 µL. Therefore, less than one drop is applied to the eyelid margin.
In the second study, eye drop application was compared to dermal application to the upper eyelid margin using dye. A supplied photo shows less green dye visible with the dermal application (Figure 1).
Figure 1. Comparison of exposure to solution applied as an eye drop compared to dermal application