IGF-1 treatment increased height in children with primary IGF-1 deficiency

LWPES/ESPE 8th Joint Meeting

Recombinant human insulin-like growth factor-1 treatment was well tolerated and resulted in dose-dependent annualized height velocities in children with primary IGF-1 deficiency, according to data from two new studies.

An 86-week, single-arm, open-label trial included 45 treatment-naive prepubertal children (mean age, 8.7 years) with primary IGF-1 deficiency (height and IGF-1 SDS <–2; simulated growth hormone level ≥7 ng/mL). Children were assigned to an initial daily rhIGF-1, also known as mecasermin (Increlex, Tercica), dose of 60 mcg/kg. In place of the approved and usual weight-based twice-daily dosing for children with severe primary IGF deficiency, once-daily doses were adjusted to achieve age-normal IGF-1 target concentrations.

At baseline, the mean height SDS was –2.7. For children who remained prepubertal, daily rhIGF-1 dosing resulted in annualized height velocities that were dose dependent from baseline to week 34 (P=.020) and from week 34 to 86 (P=.0004).

In older children, higher doses prevented the usual decline in annualized height velocities often observed in the second year of treatment, according to researcher George Bright, MD, vice president and medical director of endocrinology at Tercica, a subsidiary of Ipsen. Pharmacokinetic dosing led to doses 50% to 70% lower in younger children aged 4 to 7 years than were received by older children.

The researchers reported possible drug-related adverse events in 26 children, including headache and vomiting. Most were mild, transient and did not require dose reduction.

The study provided two lessons for IGF-1-deficient children, according to Bright. “First, the more rhIGF-1 you give, the more they grow. And secondly, pharmacokinetic dosing is not the best way for younger kids because it gives them smaller doses.”

Database findings

In a related study, analysis of the Increlex Growth Forum Database revealed dose-dependent increases in first-year height velocity and no unexpected serious adverse drug reactions with twice-daily rhIGF-1.

Researchers conducted a multicenter, open-label, observational study to assess long-term safety and efficacy of twice-daily treatment. The safety analysis included 607 children with primary IGF-1 deficiency (mean age, 10.9 years) who remained prepubertal during the first year of treatment. The efficacy analysis included 119 prepubertal children (mean age, 8 years) with height measurements and dose information available at one year.

Children were about three years behind normal height, a stature found in about one in 500 children, Barry Reiner, MD, a pediatric endocrinologist in private practice and adjunct instructor at Johns Hopkins University, told Endocrine Today. With twice-daily rhIGF-1 treatment, dose and baseline age were both significant predictors of first-year height velocity (P=.026 for age; P=.009 for dose). Reiner also said that higher doses were associated with better growth rates (average doses ranged between 40 mcg/kg and 120 mcg/kg).

The two most frequently reported targeted adverse events were hypoglycemia (7.1%) and headache (5.3%). Four serious adverse events were considered related to treatment, including intracranial hypertension and headache requiring therapy cessation.

The researchers concluded that there is no apparent relationship between dose and adverse events for the range of doses studied.

“These are findings from ‘real world’ practice settings,” Reiner said. – by Walter Alexander

We have had GH treatment for many years. There are doctors who have met children who do well on treatment, but also some who do not do well. It is important to have another option for these patients. Many doctors may be a little afraid of new therapies and the potential adverse events, but there is a strong urge to help these children. Therefore, the new IGF-1 data presented at this meeting are exciting.

– Peter Bang, MD, PhD

Associate Professor, Pediatric Endocrinology Unit, Department of Woman and Child Health
Karolinska Institute and University Hospital, Stockholm, Sweden

For more information:

• Bowlby D. PO1-108.
• Rogers D. PO1-113. Both presented at: LWPES/ESPE 8th Joint Meeting; September 9-12, 2009; New York.