Morquio A syndrome may be seen in adults, but FDA classified it as a rare pediatric disease because it begins in childhood and many patients with a severe form of the syndrome do not survive to adulthood.

The decision meant that BioMarin Pharmaceutical Inc. was eligible for (and ultimately received) the first rare pediatric disease priority review voucher upon approval of Vimizim (elosulfase alfa). The incentive program was introduced by the FDA Safety and Innovation Act of 2012.

BioMarin later sold the voucher to Sanofi and Regeneron Pharmaceuticals Inc. for $67.5 million ([A#00140811016]).

But Vimizim’s labeling raised questions about FDA thinking in awarding the voucher. The recombinant enzyme replacement therapy is indicated for pediatric and adult use.

FDA decided during its review of the application that while Morquio A syndrome affects adults, it is far more widely seen in children.

Morquio A Syndrome Registry Patient Ages
0-4 years	45
5-11 years	127
12-18 years	84
Older than 18	69
Source: BioMarin BLA data from the Morquio Clinical Assessment Program (MorCAP) as cited in FDA review documents

BioMarin estimated no more than 800 people in the U.S. have been diagnosed with Morquio A syndrome, also known as mucopolysaccharidosis type IVA, Office of Orphan Products Development medical officer John Milto noted in a Jan. 14 consulting review. OOPD had previously accepted a slightly larger target population of 1,532, but both figures are well below the prevalence threshold of 200,000 to qualify as a rare disease.

Disease onset is between ages 1 and 3. BioMarin said that 64% to 80% of patients enrolled in the International Morquio Organization registry program and its Phase III study are 18 or younger, Milto reported. Most are between 5 and 11.

Milto also pointed to a journal article that indicated 68% of patients in a registry were determined to have the severe form, and that most would not be expected to live beyond age 18.

“Based on this percentage of severe phenotype patients and given the severely limited life expectancy of the severely affected Morquio A patient, one would expect that no more than 32% of Morquio A patients would survive beyond 18 years of age,” Milto calculated.

That led the OOPD reviewer to conclude that the majority of Morquio A patients “would be younger than 18 years of age, which meets the FDASIA definition of a rare pediatric disease.”

Late OOPD Discussion Leads To Request

BioMarin submitted its voucher application well after the Vimizim BLA had been submitted. The request was dated Jan. 7 – less than six weeks before the agency approved the product ([A#06141201001]).

The agency may have played a role in encouraging the company to request the voucher. The consult indicates the request came “as a follow up” to a discussion OOPD Director Gayatri Rao held with the company on Dec. 3, 2013.

FDA appeared to be flexible in its application of the program requirements because it awarded the voucher despite giving Vimizim pediatric and adult indications Also see "BioMarin Tests FDASIA’s Pediatric Voucher Waters With Vimizim Approval" - Pink Sheet, 24 February, 2014.. The product received an orphan drug designation in May 2009.

While the pediatric rare disease voucher program was modeled on the tropical disease priority review voucher program, the requirements are less restrictive in some cases, which may make it more popular Also see "Another Chance to Make Priority Review Vouchers Work" - Pink Sheet, 22 August, 2012..

Low Survival To Adulthood Key To Vimizim Pediatric Priority Voucher

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