Nearing its Sunset, Pediatric Voucher Program Gains Momentum

By Alexander J. Varond –

On December 8, 2015, FDA approved two new therapies: Vonvendi (BLA 125577) for von Willebrand disease and Kanuma (NADA 141-453) for lysosomal acid lipase (LAL) deficiency. These approvals bring the number of new molecular entities and new therapeutic biological products approved this year to 42 (surpassing FDA’s 41 approvals in 2014). With Kanuma’s approval, FDA also issued its 6th rare pediatric disease priority review voucher to Alexion Pharmaceuticals.

The Kanuma pediatric voucher brings the number of vouchers issued since the 1-year sunset clause was triggered in March 2015 to a total of 3. In addition to the uptick in pediatric voucher issuances, the number of companies reporting that they secured rare pediatric disease designation (an optional first step on the path towards a pediatric voucher) has also markedly increased.

Priority Review Vouchers Issued

The two tables below list the vouchers that have been issued to date.

Table 1:         Tropical Disease PRVs

Table 2:         Rare Pediatric Disease PRVs

Despite the tropical disease voucher program’s approximately 7-year existence, it has been utilized much less frequently (3 vouchers/7 years = 0.4 vouchers/year) than the 3‑year old pediatric voucher program (6 vouchers/3 years = 2.0 vouchers/year). Tropical disease vouchers were first available to applications approved in September 2008, and pediatric vouchers were first available to applications submitted after October 2012.

Recently Issued Pediatric Vouchers

A short description of FDA’s three most recent approvals yielding pediatric vouchers is provided below.

Xuriden’s approval is remarkable in that the drug is intended to treat an extraordinarily rare condition, hereditary orotic aciduria. In fact, the rare metabolic disorder has a patient population of approximately 20 patients worldwide! Hereditary orotic aciduria is a rare metabolic disorder associated with blood abnormalities, urinary tract obstruction, failure to thrive, and developmental delays. The drug was evaluated in a single arm, 6-week, open-label trial in 4 patients with hereditary orotic aciduria, ranging in age from 3-19 years old and a 6-month extension trial. The study assessed changes in patients’ prespecified hematologic parameters. FDA also relied on 19 case reports from published literature.

Strensiq’s approval was for perinatal/infantile and juvenile-onset hypophosphatasia (HPP). HPP is a rare, genetic, metabolic disease characterized by defective bone mineralization. Patients also experience devastating progressive effects on multiple systems of the body, leading to severe disability and life-threatening complications, including profound muscle weakness. The most severe form of the disease occurs in newborns at a rate of approximately 1 in 100,000 births. Cases appearing in childhood and adulthood are generally less severe and occur more frequently. Four prospective, open-label studies included 99 patients with infantile- or juvenile-onset HPP on therapy for up to 6.5 years. Efficacy in patients with infantile-onset HPP was supported by improvements in overall survival at 1 year of age, ventilator-free survival at 1 year of age, skeletal manifestations, and growth compared to a natural history cohort. Efficacy in patients with juvenile-onset HPP was supported by favorable results in growth, skeletal manifestations, and gait/mobility compared to a natural history cohort.

Kanuma’s approval was for LAL deficiency, also known as Wolman disease and cholesteryl ester storage disease (CESD). Patients with LAL deficiency suffer from build-up of fats within in cells, leading to cardiovascular and liver disease and other complications. Similar to HPP, LAL deficiency presents both during infancy in a more severe form (as Wolman disease) and in childhood or later in a less severe form (as CESD). CESD is 10-25 times more prevalent than Wolman disease. Efficacy in patients with Wolman disease was supported by a historically controlled trial in 9 infants on significant differences in the survival rates at 12 months of age. Efficacy in patients with CESD was shown in a 20-week double-blind, placebo-controlled trial in 66 pediatric and adult patients on improvements in LDL-cholesterol levels and other disease-related parameters. Patients in the CESD trial were 4-58 years old (71% were less than 19 years old).