Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Growth Hormone Deficiency. 
Treatment: Skytrofa. 
The insurer denied: Skytrofa. 
The denial is overturned. 

The patient is a teenage male followed by his pediatric endocrinologist for short stature, growth hormone deficiency, and Hashimoto thyroiditis. His height was tracking close to the 25th percentile at 5 to 9 years old by report. This drifted over time to the 10th percentile by report. Bone age was read as closest to the 13-year standard at a younger chronological age. The patient did undergo growth hormone (GH) stimulation testing that he failed with peak GH of 6.51 nanograms per milliliter (ng/mL). Brain magnetic resonance imaging (MRI) was normal. The patient was started on growth hormone therapy 2 years ago. His height his current age was at the 16th percentile. His endocrinologist is prescribing Skytrofa (lonapegsomatropin-tcgd). 
Coverage was denied for not meeting criteria (preferred products are Genotropin and Norditropin). An appeal letter from his treating physician states that Norditropin is back ordered, and that the patient will undergo wilderness therapy where he will have no access to a cooling container to store his growth hormone supplies. Skytrofa is stable at room temperature. Hence, the request. 

The requested health service is medically necessary. 

The patient does have growth hormone deficiency and requires uninterrupted growth hormone treatment. However, his Plan's preferred product Norditropin is back-ordered nationally while Genotropin pen devices are in short supply. Further, the patient is in wilderness therapy and will have not access to a cool container to store his growth hormone pens. None of the current daily growth hormone injection formulations can be stored at room temperature. Skytrofa, on the other hand, may be stored at room temperatures. Since 1987, children with growth hormone deficiency (GHD) have been treated with daily injections of somatropin. Although treatment with daily somatropin is safe and provides children with the potential to achieve normal adult height, real-world outcomes have not matched expectations. Both children and their caregivers find the daily injection frequency to be burdensome, leading to nonadherence rates of 5 percent (%) to 82%. In 2015, the Growth Hormone Research Society recognized the need for a long-acting growth hormone (LAGH) and agreed that by decreasing injection frequency and offering different pharmacokinetic properties, a long-acting growth hormone would potentially improve adherence and outcomes (2). 
Lonapegsomatropin (Skytrofa, TransCon hGH; Ascendis Pharma A/S) is a once-weekly long-acting prodrug developed for children and adults with growth hormone deficiency consisting of the parent drug, somatropin, an inert methyoxy polyethelene glycol carrier, and a TransCon linker. Lonapegsomatropin is the only long-acting growth hormone that releases somatropin with the identical 191 amino acid sequence and size (22 kDa) as both endogenous growth hormone and daily somatropin therapy and is thus designed to maintain the same mode of action, distribution, and intracellular signaling. The apparent half-life of somatropin released from lonapegsomatropin is approximately 25h, as established in clinical Phase 1 trials, permitting the once-a-week dosing interval (3). Another advantage of Skytrofa is that it can be stored at room temperature, contributing to less injection site pain (4). It also reduced injections by 86% per year compared to daily injections (1). Indeed, a multi-center trial on 161 treatment-naive, pre-pubertal patients with growth hormone deficiency comparing daily somatropin versus lonapegsomatropin demonstrated non-inferiority and superiority over daily somatropin, with increase in height standard deviation score (SDS) from baseline by 1.1 versus 0.96 in the weekly lonapegsomatropin versus daily somatropin groups (1). Therefore, Skytrofa is medically necessary.