Procysbi (cysteamine bitartrate) delayed release capsules by Raptor Pharmaceuticals has been granted Orphan Drug Exclusivity (ODE) by the FDA.  The drug designed to treat nephropathic cystanosis differs from the current cysteamine bitartrate treatment in that it may be administered every 12 hours instead of the strict every 6 hours, around the clock regimen that is required of the immediate release product.  The product is approved for use in children 6 years of age and older.  The every 6 hour regimen required patients and/or caregivers to wake in the middle of the night in order to administer the medication.  Failure to follow that strict regimen could result in substantial and life threatening consequences (see below).  Now with the twice daily version, patients can enjoy a full night’s sleep and other benefits for this new every 12 hour regimen.

When it was first approved in 1994, the original cysteamine bitartrate version was granted ODE.  Typically, a second drug in a new dosage form and for the same indication would be considered the same for ODE purposes; however, the FDA letter of ODE award notes that “if a sponsor gets approval for a drug that is the “same drug” (API) as another drug that has previously had ODE for the same indication, and if the new drug is shown to be clinically superior, it won’t be considered the “same drug”. (sic)  With the grant of ODE for Procysbi, the Agency has thus decided that the new product is clinically superior to the original product, thus making it eligible for the ODE grant.  While FDA did not expand on the reasons for its decision, the firm had made various arguments in its request to support a second period of exclusivity.

In a previous post here, we reported that FDA had finalized its revised Orphan Drug Regulations.   Those regulations further explained how and when a firm may be eligible for a second period of ODE for the same drug and the same indication.  FDA exempted quality of life issues as a factor in determining significant clinical improvement; however, they allowed as a factor for consideration products that significantly improved patient compliance.  In the past, FDA had granted only a handful of designations for improved compliance (e.g., injectable product that went from once a day to once a month).  A simple dosage regimen change from 4 times a day to twice a day was not considered “significant” enough to warrant a second ODE period.  The Agency did, however, indicate that they would treat each product change on a case-by-case basis.  One of the arguments Raptor made for exclusivity included its unique dosing requirement and the health implications for failure to comply with the strict every 6 hour, around the clock regimen of the previously approved product.  How and whether or to what extent the FDA took this argument into account when making its exclusivity determination is not known, but surely the timing of the final rule and FDA’s explanation of the rationale for its thinking relative to this matter seems consistent with at least one of Raptor’s assertion that their product was indeed clinically superior to the original previously approved version of the drug.  Procysbi was granted orphan drug designation prior to filing; however, a decision on granting orphan drug exclusivity is made only after approval and is based on the totality of the studies and data submitted in the new drug application.

Regarding the disease state treated by Procysbi , Raptor noted in its press release that:

“Nephropathic cystinosis comprises 95% of cases of cystinosis, a rare, life-threatening metabolic lysosomal storage disorder that causes toxic accumulation of cystine in all cells, tissues, and organs in the body. Elevated cystine leads to progressive, irreversible tissue damage and multi-organ failure, including kidney failure, blindness, muscle wasting and premature death. Nephropathic cystinosis is usually diagnosed in infancy and requires lifelong therapy. Left untreated, the disease is usually fatal by the end of the first decade of life. There are an estimated 500 patients living in the U.S. with cystinosis and 2,000 worldwide.

Cystine depletion is the primary treatment strategy for nephropathic cystinosis. However, poor adherence to therapy has been a major challenge resulting in poor sustained control of cystine levels, and patients consequently experience poor clinical outcomes, including kidney insufficiency leading to dialysis and kidney transplantation, muscle wasting and in some cases, premature death. Even brief interruptions in daily therapy can permit toxic accumulation of cystine, exposing tissues to renewed, progressive deterioration.”

Lachman Consultants has worked closely with Raptor in this process to gain approval for their Procysbi product.   We are very pleased not only with the success in approval of this critical drug for a very small patient population, but are particularly excited about the ODE award for this “ultra-orphan” drug the firm received yesterday.   If you have additional questions or need assistance with Orphan Drug questions, please contact Joan Janulis at