Regulatory Decision Summary for NATESTO

Natesto was evaluated for safety and efficacy in a 90-day, open-label, multicentre trial of 306 hypogonadal men. Eligible patients were 18 years of age and older (mean age 54 years) and had morning serum total testosterone concentrations less than 300 ng/dL. Patients were Caucasian (89%), African-American (6%), Asian (5%), or of other ethnicities (less than 1%).

Patients were instructed to self-administer Natesto (11.0 mg of testosterone) intranasally either two or three times daily. On Day 45, patients were either maintained at the same dose or titrated to three times a day, based on the assessment of 24 hour average serum testosterone concentration. The primary endpoint was the percentage of patients with an average serum total testosterone concentration (Cavg) within the normal range (300 to 1,050 ng/dL) on Day 90. At the end of the treatment period (Day 90), 122 patients were receiving 22.0 mg of testosterone twice daily (BID) and 152 patients were receiving 33.0 mg of testosterone three times daily (TID).

Among these patients, 71% who received 22.0 mg of testosterone daily and 76% who received 33.0 mg of testosterone daily had Cavg within the normal range on Day 90. Of the 273 patients who completed the 90-day treatment, 237 patients did so with no deviation from the protocol. For this population, 75% who received 22.0 mg of testosterone daily and 77% who received 33.0 mg of testosterone daily had Cavg within the normal range on Day 90. Results of secondary endpoints correlated with the primary endpoint. 

The safety of Natesto was also evaluated in this pivotal trial. Patients could continue treatment with Natesto in two, open-label safety extension periods for an additional 90 and 180 days, respectively. The most commonly reported (≥2% of subjects) adverse drug reactions (ADRs) in the 90-day treatment period of Natesto were: serum prostate specific antigen (PSA) increased, weight increased, myalgia, parosmia, dysgeusia, rhinorrhoea, epistaxis, nasal discomfort, nasal dryness, nasal congestion, upper-airway cough syndrome and scab. In the two extension safety periods, in general, the overall percentages of patients with ADRs were comparable with those in the treatment period.

Overall, Natesto was found effective as a testosterone replacement therapy in adults males in the context of the clinical trial described above. The overall benefit-risk balance is considered positive.