DR Cysteamine for Cystinosis

Raptor's DR Cysteamine product candidate is a delayed-release oral formulation of cysteamine bitartrate. We are investigating DR Cysteamine as a potential improvement in the management of nephropathic cystinosis (cystinosis), a serious lysosomal storage disease. The disease is primarily diagnosed in early childhood.

Cysteamine therapy may be effective at preventing or delaying kidney transplants in cystinosis patients.1,2,3,4 However, patient compliance is challenging due to frequent dosing and gastrointestinal side effects.2,4,5,6

Raptor's DR Cysteamine for cystinosis was designed to potentially mitigate some of these difficulties. It is expected to be dosed twice daily, compared to the current every-six-hour dosing schedule. In addition, DR Cysteamine is designed to pass through the stomach and deliver the drug directly to the small intestine, where it may be more easily absorbed into the bloodstream and may result in fewer gastrointestinal side effects.7

Development Status for DR Cysteamine for Cystinosis

In November 2009, Raptor completed its Phase 2b clinical trial of DR Cysteamine in cystinosis. DR Cysteamine demonstrated improved tolerability and the potential to reduce total daily dosage and administration frequency compared to immediate-release cysteamine bitartrate. Specific trial results that support this finding include:

  • Pharmacokinetic evaluation showed that DR Cysteamine had a terminal half-life more than three times longer than the terminal half-life of immediate-release cysteamine bitartrate capsules.
  • Twice-daily DR Cysteamine may achieve the same pharmacodynamic result while using a daily dose 30% lower than immediate-release cysteamine bitartrate capsules administered four times daily

Raptor plans to follow the Phase 2b clinical study with a pivotal, Phase 3 clinical study at multiple sites in the US and Europe. This phase 3 trial is expected to start in the first quarter of 2010.

Raptor's phase 2b clinical trial followed earlier clinical trials with an enteric-coated cysteamine prototype conducted by Ranjan Dohil, M.D., Associate Professor of Pediatrics at University of California, San Diego (UCSD) and funded by the Cystinosis Research Foundation ("CRF"). The CRF also supported Raptor's phase 2b clinical trial.

The FDA granted orphan drug designation for DR Cysteamine for the treatment of cystinosis in 2006.


Learn more about Raptor's other clinical programs:

References:

  1. Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Annals of Internal Medicine. 2007;147:242-250.
  2. Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA, Blom HJ. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006;21:110–113.
  3. Markello TC, Bernardini IM, Gahl WA. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med. 1993;328:1157-1162.
  4. Kleta R, Bernadini IM, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, Gahl WA. Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr. 2004; 145:555-60.
  5. Kleta R, Gahl WA. Pharmacological treatment of nephropathic cystinosis with cysteamine. Expert Opin. Pharmacother. 2004;5(11):2255-2262.
  6. http://www.fda.gov/medwatch/SAFETY/2007/Jun_PI/Cystagon_PI.pdf
  7. Dohil R, Fidler M, Barshop BA, Martin M, Gangoiti J, Deutsch R, Schneider JA. Understanding intestinal cysteamine bitartrate absorption. J Pediatr. 2006;148:764-769.