By April 30, 2013, the United States Food and Drug Administration (FDA) will decide whether to approve Raptor Pharmaceutical's (RPTP) drug Procysbi for the treatment of nephropathic cystinosis. Despite the FDA's recent postponement of its decision regarding Procysbi, Raptor has convincingly shown that this drug is efficacious and safe. Relative to the existing standard of care, Procysbi offers fewer side effects and a simpler dosing schedule for cystinosis patients. These benefits promote drug compliance, which is essential for controlling disease progression. As discussed in more detail below, we believe Procysbi will receive a positive response from the FDA. Procysbi would be Raptor's first FDA-approved drug, so its approval may substantially increase the company's stock price.
Raptor Pharmaceutical is a biopharmaceutical company developing products for patients with severe, rare diseases. Its lead product candidate, Procysbi, is under FDA review for the treatment of nephropathic cystinosis, an orphan disease afflicting 2,000 patients worldwide, 500 of whom are in the US.
Nephropathic cystinosis (abbreviated "cystinosis") is a rare inherited metabolic disorder resulting from mutations in the gene CTNS. These CTNS mutations impair removal of the amino acid cystine from lysosomes, a component of human cells. As a result, cystine accumulates in lysosomes, leading to the formation of cystine crystals throughout the body. As early as six months after birth, patients experience growth retardation and rickets, a condition known as Fanconi syndrome. If left untreated, patients often develop chronic kidney failure by 10 years of age.
The standard of care for cystinosis is Mylan Pharmaceuticals' (MYL) drug Cystagon, which was approved by the FDA in 1994. After being ingested, the active component of this drug enters the lysosome and interacts with local cystine, forming cysteine-cysteamine, a compound that easily exits the cell. Cystagon treatment usually delays kidney malfunction and lessens other clinical manifestations, but it is far from perfect. The drug must be taken every six hours and its side effects include pronounced gastrointestinal distress and a pungent odor that can be socially troublesome. Consequently, patients often forgo doses, resulting in suboptimal disease prevention.
Procysbi improves patient compliance
Cystagon and Procysbi share the same active component, cysteamine. However, unlike Cystagon, Procysbi delivers cysteamine using enteric-coated microbeads, which allow for extended release of the drug. Procysbi's phase III clinical trial results show that Procysbi is as efficacious as Cystagon and ameliorates Cystagon's negative side effects. This trial was an open-label, randomized crossover trial with 43 patients at 8 sites. It evaluated whether patients had a cystine level below a threshold indicative of effective treatment. The study's readout was the amount of cystine in white blood cells, which is thought to be a reliable indicator. During the study, both Cystagon and Procysbi maintained cystine below the targeted level and Procysbi did so with a single dose for 12 hours, a time period well beyond the standard interval between doses of Cystagon.
Notably, Procysbi would be given every twelve hours. Patients currently on Cystagon should adhere to a six-hour dosing schedule, including through the night. Procysbi allows patients an uninterrupted night of rest, which especially eases the burden of treating pediatric patients. Furthermore, young patients on Cystagon who switch to Procysbi could eliminate a dose during the school day. This may substantially improve their psychological well being, because Cystagon causes a noticeable rotten egg smell after administration. Procysbi causes a much less pungent odor. Additionally, given that such odor occurs in its most pronounced form shortly after drug ingestion, Procysbi reduces the overall number of occurrences as well.
Overall, Procysbi treats cystinosis as effectively as Cystagon and reduces the social and administrative complexities that accompany Cystagon. Procysbi should improve drug compliance and, therefore, positively affect long-term disease outcomes.
The FDA's delay for Procysbi should not materially affect its decision
On December 21, 2012, Raptor announced that the FDA will require additional time to review the NDA application for Procysbi. The FDA did not ask the company for additional clinical studies. Notably, Raptor recently completed its Procysbi extension study addressing the long-term efficacy of Procysbi. The study shows that patients on Procysbi have well-managed cystine levels, preserved kidney function, and improved social function across 17 months of treatment. Due to its delayed decision, the FDA may now be able to fully incorporate these extension study results into its analysis, which bolsters the likelihood of approval.
From scientific and clinical perspectives, Procysbi is an efficacious and safe drug for cystinosis. Procysbi overcomes many compliance challenges by easing the dosing schedule and treatment side effects. We anticipate the FDA will approve Procysbi by the upcoming action date and, therefore, see Raptor stock as an attractive investment.
Disclosure: I have no positions in any stocks mentioned, but may initiate a long position in RPTP over the next 72 hours.
Additional disclosure: Beacon VP Investments is a team of analysts. This article was written by Natalie Yu, one of our team members.