Tony Hagen is senior managing editor for The Center for Biosimilars®.
A postmarketing surveillance study of Omnitrope in pediatric patients with growth hormone deficiency sheds new light on how this agent performs relative to its reference product.
Results of a subset of pediatric patients enrolled in a postmarketing surveillance study of biosimilar somatropin (Omnitrope) demonstrate that the recombinant growth hormone was safe and effective, investigators reported in an update to the PATRO Children trial.
Although marketed as a biosimilar in Europe, Omnitrope was approved via a new drug application under the Hatch-Waxman Act in the United States. The Sandoz product references Pfizer’s Genotropin. Results were presented for a subpopulation of patients (n = 291) recruited in Italy, with a mean age of 10 years (56% male).
Omnitrope is indicated for growth deficiency conditions in infants, children, and adolescents, such as Turner syndrome, chronic renal insufficiency, and Prader—Willi syndrome (PWS).
Patients received somatropin treatment for an average of 33.1 months and reported 48 adverse events (AEs), with a suspected relationship to the drug in 35 (12%) patients. Those AEs were most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal, abdominal pain, acute gastroenteritis, and pain in extremity.
Given prior concerns about a potential link between somatropin and diabetes development, the investigators said they were alert to possible incidence of type 1 or type 2 diabetes but found none, although 2 patients had impaired glucose tolerance that was linked to Omnitrope.
They measured the effectiveness of somatropin according to height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS). Mean HSDS increased from −2.41 (0.73) at baseline (n = 238) to −0.91 (0.68) at 6.5 years of treatment (n = 10). Mean HVSDS increased from −1.77 (1.38) at baseline (n = 136) to 0.96 (1.13) at 6.5 years (n = 10). Scores were different for males vs females.
The primary end point was long-term safety in infants, children, and adolescents, including in patients with PWS, and a secondary end point was long-term effectiveness.
Most patients (95.5%) were treatment naïve to hormone therapy at enrollment. At the time of analysis, treatment had been discontinued in 140 of the 291 patients. Reasons for discontinuation included patients reached final bone/height maturation (32.9%), switched to other growth hormone drugs (15%), did not respond (2.9%), experienced AEs (2.1%), and failed to comply with treatment (1.4%). Investigators said follow-up was not possible for 13.6% of patients.
Among 43 AEs with a suspected relationship to the drug, 10.7% were mild and 1.4% were moderate in intensity. Complete resolution was reported for 34 AEs (8.6%).
The investigators reported 35 serious AEs in 7.2% of patients (n = 21). The 2 serious AEs included 1 patient with gait disturbances and worsening walking difficulties and another patient with a minimal increase in a known residual craniopharyngioma, a resurgence that was not definitively linked to the somatropin biosimilar.
Investigators said HSDS and HVSDS appeared to increase from 6.5 to 8.5 years of treatment, but the number of patients during this interval (<10) was low so they did not do a formal analysis.
At 3 years of treatment, patients with Turner syndrome had the highest HSDS and HVSDS. At 6.0 years of treatment, patients born small for gestational age had higher HSDS and HVSDS compared with patients who had growth hormone deficiency.
HSDS was lower in males than females at 3 years of treatment (−1.48 vs −1.43) and 6 years (−0.95 vs −0.85), but HVSDS was higher in males than females at 3 years (1.19 vs 1.11) and 6 years (1.44 vs 0.94).
No new safety signals were discovered during the study, and the investigators concluded the biosimilar was effective and well tolerated over the long term (8.5 years).
Lughetti L, Antoniazzi F, Giavoli C, et al. Safety and effectiveness of a somatropin biosimilar in children requiring growth hormone treatment: second analysis of the PATRO Children study Italian cohort. J Endocrinol invest. Published online June 15, 2020. doi:10.1007/s40618-020-01331-4