New FDA Orphan Drugs: iPlex, Cethrin, Brivaracetam

Yael Waknine

December 13, 2005

Dec. 13, 2005 -- The US Food and Drug Administration (FDA) has approved orphan drug status for mecasermin rinfabate [rDNA origin] subcutaneous injection in the treatment of children with severe primary insulin-like growth factor-1 deficiency; BA-210 in the treatment of acute thoracic and cervical spinal cord injuries; and UCB-34714 in the treatment of symptomatic myoclonus.


Orphan Drug Mecasermin Rinfabate (iPlex) for Severe Primary IGF-1 Deficiency

On December 12, the FDA approved orphan drug status for mecasermin rinfabate [rDNA origin] injection (iPlex, formerly known as SomatoKine and made by Insmed, Inc) for the treatment of growth failure in children with severe primary insulin-like growth factor-1 (IGF-1) deficiency (primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Mecasermin rinfabate is a human recombinant protein complex of IGF-1 that is differentiated from mecasermin (Increlex, made by Tercica, Inc) by the addition of insulin-like growth factor binding protein-3 (IGFBP-3). In the bound state, IGF-1 is inactive in the blood until delivered to target tissues, thereby reducing the risk of short- and long-term adverse events that have been associated with unrestrained levels of free IGF-1.

The product is administered as a once-daily subcutaneous injection to restore and maintain physiologically relevant IGF-1 levels. According to a company news release, it is the only approved once-daily IGF-1 replacement therapy available to treat children with severe short stature.

The approval was based in part on data from a study of 29 prepubertal patients with an average height velocity of 3.0 cm/year (1.2 inches/year) who were treated with mecasermin rinfabate at doses of 0.5 to 2.0 mg/kg daily.

At 1 year, data from 16 evaluable patients treated with a low fixed dose (up to 1.0 mg/kg) showed significant increases in height velocity among those who achieved IGF-1 blood levels in the normal target range compared with those who did not (8.3 vs 5.6 cm/year; P < .0001).

In the second subset of evaluable patients (n = 9), individualized dose uptitration based on IGF-1 levels and clinical outcome (maximum dose, 2.0 mg/kg) yielded an average 9-month annualized height velocity of 8.2 cm/year, a 6.0 cm/year increase over the baseline velocity of 2.2 cm/year ( P < .0001).

According to the news release, mecasermin rinfabate was well tolerated, with a lower frequency of severe hypoglycemia and other serious adverse events than that reported in published studies of free IFG-1 therapies. In addition, no hypoglycemic convulsions or cases of facial nerve paralysis were observed.

Although a proportion of patients developed antibodies to the protein, testing revealed no evidence that their presence resulted in neutralization of biologic activity (such as decreased height velocity), adverse drug reactions, or adverse physical findings.

Mecasermin rinfabate was previously granted orphan drug status for the treatment of growth hormone deficiency by the European Medicines Evaluation Agency. It is also being evaluated for use in treating extreme insulin resistance, HIV-associated lipodystrophy, severe burn injury, and hip fractures.


Orphan Drug BA-210 (Cethrin) for Acute Thoracic and Cervical Spinal Cord Injuries

On December 12, the FDA approved orphan drug status for BA-210 (Cethrin, made by BioAxoneTherapeutic, Inc) in the treatment of acute thoracic and cervical spinal cord injuries.

The product consists of a recombinant protein Rho GTPase antagonist and a fibrin sealant to optimize its delivery during spinal restabilization surgery. After acute injury, axon regeneration inhibition is exacerbated by enhanced activity of the Rho/Rho kinase pathway that induces apoptosis in neurons, astrocytes, and oligodendrocytes.

According to a company news release, data from preclinical studies has shown that inhibition of Rho by BA-210 promoted neurite regrowth, reduced injury-related apoptosis, and improved locomotor functional recovery.

The company is currently recruiting patients with spinal cord injury for a phase 1/2a multicenter, open-label, dose-escalating safety and efficacy trial.


Orphan Drug UCB-34714 (Brivaracetam) for Symptomatic Myoclonus

On November 9, the FDA approved orphan drug status for UCB-34714 (Brivaracetam, made by UCB Pharma, Inc) in the treatment of symptomatic myoclonus.

The orally active, high-affinity synaptic vesicle protein 2A (SV2A) ligand is differentiated from levetiracetam (Keppra, made by UCB Pharma, Inc) by its mechanism of action. According to a company news release, UCB-34714 has shown significant antiepileptic activity in experimental models of epilepsy and myoclonus, as well as in a photosensitive epilepsy model in humans.

The product is currently in phase 2 clinical trials of patients with refractory partial onset seizures and in patients with postherpetic neuralgia.

UCB-34714 was previously granted orphan drug status by the European Medicines Evaluation Agency for the treatment of progressive myoclonic epilepsies.

Reviewed by Gary D. Vogin, MD

Comments

3090D553-9492-4563-8681-AD288FA52ACE
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.

processing....