Regulatory Decision Summary for Norditropin Nordiflex

Noonan syndrome (NS) is a rare (1 in 1,000 to 2,500 live births), multi-systemic disorder which may occur spontaneously or as an autosomal dominant or recessive form with similar frequency in both males and females.

The diagnosis of NS is made clinically by observing the cardinal features including typical facial features, short stature, congenital heart defects, a broad or webbed neck, and chest deformity. Some of these features (such as short stature) may have negative impacts on education, human relations and friendships resulting in low quality of life.

Short stature, defined as height below 2 standard deviation score (SDS) per national reference, affects 50-70% of NS patients. At this time, no GH based compounds are approved for short stature due to NS.

The efficacy and safety of Norditropin (0.033 mg/kg/day and 0.066 mg/kg/day) was evaluated in a phase 3, randomized, double-blind trial in 51 Japanese children aged 3 and older with short stature (mean height < -3 SDS at baseline) due to NS. 

A growth promoting effect was observed during the 104 week treatment period – with 9 (36%) children in the 0.033 mg/kg/day group and 15 (58%) children in the 0.066 mg/kg/day group achieved a height within the normal national range, defined as height SDS above -2.

The safety data from this pivotal study were limited by the small sample size and duration of the study (up to 208 weeks).

However, the safety profile of GH is well established from decades of use in pediatric patients with short stature. There was no new safety issue identified in the submitted studies.

Although not specifically evaluated, based on the observations of height improvement and its associated mental, psychological and social benefits in children with short stature due to GH deficiency, small for gestation and Turner syndrome, it is anticipated that a height improvement in NS children with short stature would produce similar benefits.

At present, there are no GH products that have Noonan syndrome as an approved indication in Canada. The treatment with Norditropin will therefore meet an unmet medical need.

The overall benefit/risk profile is considered acceptable for Norditropin when used in pediatric patients with short stature due to NS.