BOSTON — An investigational long-acting form of recombinant human growth hormone (rhGH) given twice a month has achieved efficacy and safety at 2 years, new data show.
The novel long-acting recombinant human growth hormone fusion protein somavaratan (Versartis) with a serum half-life of > 100 hours is under development for children and adults with growth-hormone deficiency.
When injected subcutaneously twice monthly, it maintained insulinlike growth factor-1 (IGF-1) in the normal range without overexposure and led to continued catch-up growth through the first 2 years of treatment with no safety signals, George M Bright, MD, vice president of clinical development at Versartis, reported April 3 in a late-breaking clinical session at the annual meeting of the Endocrine Society, ENDO 2016.
"Not all children are able to achieve complete adherence with daily administration.…Long-acting growth hormone offers the possibility of reduced treatment burden, an increase in treatment adherence, and with that an increase in treatment outcome," Dr Bright said during his presentation, noting that noncompliance has been reported in up to 77% of adults and children with growth-hormone deficiency (Endocr Pract. 2008;14:143-154).
Dr Bright told Medscape Medical News, "During 2 years of somavaratan [therapy], we have the hoped-for treatment effects, with a benign safety profile….Kinetic, dynamic information tells us this is a very well-behaved drug."
Asked to comment, session moderator Gary D Hammer, MD, PhD, director of the endocrine oncology program at the University of Michigan, Ann Arbor, called the data "intriguing," adding, "We certainly know that compliance is a big issue in the pediatric population and in adults as well. This may be more patient-friendly."
No Safety Issues Seen
Previously, somavaratan had been tested in a phase 1 trial in adults and in a phase 1b/2a study of three dosing schedules in 64 prepubertal children (J Clin Endocrinol Metab 2016;101;1091-1097), in whom clinically meaningful improvements were seen at 1 year in height velocity and IGF-1, which is used as a surrogate marker for effects of growth-hormone treatment. No unexpected or study-drug–related serious adverse events occurred.
The current data come from a continuation of the children's study as a 12- to 24-month open-label extension trial, during which 57 of the patients received the highest of three somavaratan doses that had been tested during months 6 through 12: 3.5 mg/kg injected twice monthly.
The patients had a mean age of 8.8 years, were mostly white (82.5%), and 58% were male. At baseline they had moderate growth-hormone deficiency, with average height standard deviation score (HT-SDS) -2.6, IGF-SDS -1.5, and mean stimulated GHmax 5.3 ng/mL.
At-home adherence to both the expected number of injections and the dose was greater than 99% (99.4% and 99.6%, respectively).
"We're very happy to be able to report that, consistent with our rationale for developing long-acting growth hormone, we achieved very good adherence," Dr Bright commented.
There were no treatment-related serious adverse events, and no lipoatrophy or nodules at injection sites.
All adverse events were mild to moderate, transient, and similar to those seen with the daily growth-hormone treatment, including injection-site erythema and pain, arthralgia, and headache. However, only injection-site pain occurred in more than 10% in the first 6 months (45%), and by months 18 to 24 even that was down to just 2%.
No adverse event occurred in more than 4% of patients at 18 to 24 months, despite an increase in dose over the 2-year period, Dr Bright noted.
During treatment, there were 10 instances of IGF-1 SDS between 2.0 and 3.0 in seven patients and two instances of IGF-1 SDS above 3.0 in two patients. However, all were transient and none were associated with concurrent adverse effects, he said.
Two-Year Efficacy Similar to Daily Dosing
During the first year with randomization to the multiple dosing regimens (1.15 mg/kg weekly, 2.5 mg/kg twice-monthly, 3.5 mg/kg twice monthly, or 5.0 mg/kg monthly), mean height velocity was 8.08 cm/year.
At the end of year 2, during which all the subjects were on 3.5 mg/kg twice monthly, mean height velocity was comparable to the first year, at 7.83 cm/year.
"By virtue perhaps of increasing the dose, we did not observe a fall in height velocity in the second year," Dr Bright commented.
By comparison, he noted that a prior European trial of daily rhGH in 8-year-old children with moderate growth-hormone deficiency showed a second-year height velocity of 6.9 cm/year with a daily dose of 34 µg/kg/day (J Clin Endocrinol Metab. 2010;95:1229–1237), while an American database analysis showed average second-year height velocity of 7.9 cm/year with a daily dose of 43 µg/kg/day (J Clin Endocrinol Metab. 2010;93:352–357).
Dr Hammer noted, however, "[Dr Bright] presented historic data. Whether or not the company wishes to do a head-to-head study wasn't discussed."
Nonetheless, he said, "It's very exciting."
In conclusion, Dr Bright said that in prepubertal children with moderate growth-hormone deficiency, twice-monthly somavaratan treatment maintained IGF-I in the normal range without overexposure and provided continuing catch-up growth through the first 2 years.
Somavaratan 3.5 mg/kg twice-monthly is now under study in a randomized, phase 3, noninferiority trial vs daily rhGH in pre-pubertal children with growth-hormone deficiency.
Versartis supported the study. Dr Bright is a consultant to and holds equity interests in Versartis. Disclosures for the coauthors are listed in the abstract. Dr Hammer is a consultant for Atterocor, Orphagen, HRA Pharma, and Embara, and is founder of Atterocor.
ENDO 2016; April 3, 2016; Boston, Massachusetts. Abstract LB-OR02-2
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Cite this: Investigational Long-Acting Growth Hormone Shows Promise - Medscape - Apr 12, 2016.