EU Gives Okay to Two Drugs for Rare Pediatric Endocrine Disorders

Miriam E Tucker

December 18, 2017

The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the use of special regulatory processes to facilitate licensure of two medications that address unmet needs for two rare pediatric endocrine disorders.

The medications are hydrocortisone granules in capsules for opening (Alkindi, Diurnal) for the treatment of primary adrenal insufficiency in infants, children, and adolescents, and burosumab (Crysvita, Kyowa Hakko Kirin/Ultragenyx Pharmaceutical) for the treatment of X-linked hypophosphatemia (XLH) with radiographic evidence of bone disease in children 1 year of age and older and adolescents with growing skeletons.

CHMP has issued positive opinions on the two regulatory processes, which means that, barring any unforeseen obstacles, the formal approvals will come within 60 days.

A New Hydrocortisone Formulation

For Alkindi, the panel recommended granting a pediatric-use marketing authorization (PUMA), a process used for pediatric formulations of medicines that are already on the market and no longer under patent protection. The PUMA designation grants the manufacturer 10 years of market protection. 

Pediatric adrenal insufficiency is designated as a rare disease in Europe, with approximately 4000 sufferers younger than 6 years. Treatment is with hydrocortisone, but there is currently no pediatric version available, so the adult-formulated 10-mg capsules are typically crushed or compounded for children.

Alkindi will be available as 0.5-mg, 1.0-mg, 2.0-mg and 5.0-mg granules of hydrocortisone in capsules for opening, thereby allowing for more precise dosing. The new product also masks the bitter taste of the active substance, thereby better ensuring that children actually swallow the medication.

The positive opinion from CHMP is based on a review of data from the company's pivotal open-label phase 3 clinical trial conducted in 24 subjects younger than 6 years who require replacement therapy for adrenal insufficiency due to congenital adrenal hyperplasia, primary adrenal failure, or hypopituitarism.

The study successfully met its primary end point and no serious adverse events were reported, according to a Diurnal statement.

CHMP recommended the product's use in patients up to 18 years of age, but marketing will be focused primarily on ages 0 to 6 years, where the unmet need is highest. The product is expected to launch in the European Union in the second quarter of 2018.

Conditional Approval for X-Linked Hypophosphatemia Treatment

X-linked hypophosphatemia (XLH) is a rare, inherited, chronic progressive musculoskeletal disorder characterized by renal phosphate wasting caused by excess phosphaturic hormone fibroblast growth factor 23 (FGF23) production. It affects both males and females, causing lower-extremity deformity (rickets), short stature, bone pain, and severe dental pain.

Conventional treatment consists of multiple daily doses of phosphate and active vitamin D to counteract the excess effects of FGF23 but doesn't correct the underlying defect.

Burosumab, an anti-FGF23 human monoclonal antibody, would be the first therapy to do so. CHMP recommended "conditional" approval for burosumab to treat XLH based on two phase 2 studies. The main one, in 53 children aged 5 to 12 years, demonstrated improved phosphate levels and renal reabsorption of phosphate, as well as radiographic improvement of rickets. Responses were similar in the second study, of 13 children aged 1 to 4 years.

The most common adverse reactions were injection-site reactions, headache, and extremity pain.

The panel advised that burosumab be prescribed by physicians experienced in managing patients with metabolic bone diseases.

Burosumab had received an orphan designation from the EMA's Committee for Orphan Medicinal Products in October 2015.

The CHMP recommendation for conditional approval would allow the product to be marketed to meet an immediate unmet need, while requiring the manufacturers to complete three ongoing studies to further assess safety and efficacy before full marketing is granted. Those data are expected to be submitted by 2020.

In the United States, the Food and Drug Administration is currently reviewing the Biologics License Application for burosumab to treat pediatric and adult patients with XLH, with a Prescription Drug User Fee Act action date of April 17, 2018.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.