Raptor Pharmaceutical Meets Primary Endpoint in Its Phase 3 Clinical Trial of DR Cysteamine for Nephropathic Cystinosis

NOVATO, Calif., Jul 25, 2011 (GlobeNewswire via COMTEX) -- Raptor Pharmaceutical Corp. ("Raptor" or the "Company") today announced that its Phase 3 clinical trial of Delayed Release or DR Cysteamine, known as study drug RP103 ("RP103"), for the treatment of nephropathic cystinosis, met the primary endpoint of non-inferiority compared to Cystagon(R), immediate-release cysteamine bitartrate. The comparison was based on white blood cell ("WBC") cystine levels, the established efficacy surrogate biomarker and sole primary endpoint in the clinical trial. The Company also reported that there were no unexpected serious safety concerns experienced by patients in the trial attributable to RP103.

Nephropathic cystinosis is a severe ultra-orphan inherited condition which results in premature death if not treated. The current standard of care for cystinosis is oral Cystagon(R), immediate-release cysteamine bitartrate, which must be taken strictly every 6 hours, including a middle-of-the-night dose. Lack of compliance with the strict dosing schedule of Cystagon(R) has been widely reported to be a significant challenge in the therapeutic management of cystinosis patients. RP103 is Raptor's proprietary, twice-daily formulation of cysteamine bitartrate, designed for reduced dose frequency and improved tolerability for the treatment of cystinosis. Raptor's pivotal Phase 3 clinical trial was designed as an outpatient study of the pharmacodynamics, pharmacokinetics, safety and tolerability of RP103 compared to Cystagon(R) in cystinosis patients. The clinical trial was conducted at eight clinical research centers in the US and Europe.

Of 41 patients who completed the Phase 3 protocol, 38 were included in the evaluable data set, 3 not being fully compliant with the protocol. The age range of study participants was 6-26 years, with 87% of patients below 16 years old. On average, the peak WBC cystine level measured in patients treated with Cystagon(R) was 0.54 +/- 0.05 nmol 1/2 cystine/mg protein, compared to an average peak value of 0.62 +/- 0.05 nmol 1/2 cystine/mg protein for patients treated with RP103. The mean difference was 0.08 nmol 1/2 cystine/mg protein, with a 95.8% confidence interval of 0.00-0.16 (one sided p=0.021). As stipulated in the Statistical Analysis Plan, the non-inferiority endpoint of the clinical trial would be achieved when the upper end of the confidence interval around the mean difference of WBC cystine levels did not exceed an absolute value of 0.3. The upper end of the confidence interval in the Phase 3 clinical trial was determined to be 0.16, thus achieving the non-inferiority endpoint.

"We are obviously very excited to have successfully met our primary endpoint of this study," said Christopher M. Starr, Ph.D. and CEO of Raptor, "and we would like to sincerely thank all the study participants, families and study coordinators for their time and effort in helping us complete this study."

Additionally, the endpoint was achieved at a lower average daily dose of RP103, compared to Cystagon(R). Patients enrolled in the study were required to be "well controlled" under the existing Cystagon(R) therapy. The starting dose of RP103 for patients in the Phase 3 clinical trial was initially set at 70% of their established dose of Cystagon(R). The protocol allowed for a single RP103 dose increase of 25%, based on intermediate WBC cystine results, to reflect the current standard of care in establishing appropriate dosing of Cystagon(R) in cystinosis patients. Approximately one-third of patients remained at 70% of their starting Cystagon(R) dose throughout the study. The remaining two-thirds of the patients had their RP103 dose increased. On average, the total daily, steady-state dose of RP103 in patients in the Phase 3 clinical trial was 82% of their established, incoming dose of Cystagon(R).

In the course of the study, seven serious adverse events ("SAEs") requiring a visit to the emergency room or hospital, were reported for seven individual patients. Of these seven SAEs, six were determined by the Principal Investigator to be unrelated to either RP103 or Cystagon(R). One SAE, gastric intolerance, was graded as "possibly related" to RP103 and was subsequently resolved. Further analyses of non-serious adverse events ("AEs") are underway by the Company's statistical contractor.

The Company is conducting an ongoing, extension study in which all patients completing the Phase 3 clinical trial may elect to continue on RP103 treatment and are monitored for WBC cystine levels and safety parameters. The extension study will provide at least six months of safety data for each patient and will be part of Raptor's New Drug Application filing. Thirty-two patients have been on RP103 in the extension study for at least 6 months.

Additional Successful Bioequivalence Study Announced

In a related clinical trial, Raptor demonstrated bioequivalence between RP103 administered as whole capsules and administered as capsule contents sprinkled onto applesauce. As a significant number of cystinosis patients are too young to take whole capsules, this result may enable the Company to expand enrollment in the extension study to patients who are too young to swallow whole capsules and were therefore ineligible for the pivotal Phase 3 clinical trial protocol.

In addition to the planned submission of the clinical data for publication, Raptor will present the top line clinical data at the Canaccord Genuity Annual Growth Conference on August 9th in Boston, MA and at the Wedbush Securities Life Sciences Management Access Conference on August 16th in New York, NY.

About Nephropathic Cystinosis

Nephropathic cystinosis is an inborn metabolic error characterized by the abnormal transport of cystine, an amino acid, out of the lysosomes. Poor compliance with current treatments for nephropathic cystinosis can cause serious health consequences, including: renal failure and resultant need for a kidney transplant; growth failure; rickets and fractures; and photophobia and blindness. Symptom onset typically occurs within the first year of life, when cystine crystals accumulate in various tissues and organs, including the kidneys, brain, liver, thyroid, pancreas, muscles and eyes.

About Cysteamine and RP103

RP103 is Raptor's proprietary enteric-coated, microbead oral formulation of cysteamine bitartrate designed to potentially reduce dosing frequency and reduce gastrointestinal side effects associated with immediate-release cysteamine bitartrate, which is approved for sale by the US Food and Drug Administration ("FDA") and the European Medicines Agency ("EMA") to treat nephropathic cystinosis. Raptor has been granted orphan product designation for RP103 by the EMA and FDA.

In December 2007, Raptor obtained an exclusive, worldwide license from the University of California, San Diego for the development DR Cysteamine for nephropathic cystinosis and cysteamine for other potential indications including Huntington's Disease, and Non-alcoholic Steatohepatitis ("NASH").

About Raptor Pharmaceutical Corp.

Raptor Pharmaceutical Corp. /quotes/zigman/114629/quotes/nls/rptp RPTP -24.28% ("Raptor") seeks to research, produce, and deliver medicines that improve life for patients with severe, rare disorders. Raptor currently has product candidates in clinical development designed to potentially treat nephropathic cystinosis, Non-alcoholic Steatohepatitis ("NASH"), Huntington's Disease ("HD"), aldehyde dehydrogenase deficiency ("ALDH2"), and thrombotic disorder.

Raptor's preclinical programs are based upon bioengineered novel drug candidates and drug-targeting platforms derived from the human receptor-associated protein and related proteins that are designed to target cancer, neurodegenerative disorders and infectious diseases.

For additional information, please visit www.raptorpharma.com .

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