Orphan Drug Designation Not Sacrosanct – FDA Revokes Orphan Designation for TheraCLEC for EPI, but Other Exclusivity Issues Remain

In a July 3, 2007 filing with the Securities and Exchange Commission (“SEC”), Altus Pharmaceuticals Inc. announced that the company was notified by FDA’s Office of Orphan Products Development (“OOPD”) that the orphan drug designation granted in January 2002 to ALTU-135, also know as TheraCLEC, for the treatment of Exocrine Pancreatic Insufficiency (“EPI”) was being revoked.  OOPD only very rarely revokes orphan drug designation.  According to the Altus filing, “[t]he FDA based its decision on a finding that if one includes all patients with HIV/AIDS who suffer from fat malabsorbtion in this indication, the patient population in the United States appears to exceed 200,000 persons and is thus ineligible for orphan drug designation.”  A March 2007 Altus SEC filing noted that FDA first informed the company in December 2006 of the Agency’s plans to revoke the TheraCLEC orphan drug designation.

TheraCLEC is a Pancreatic Exocrine Product (“PEP”) in clinical development that contains the enzymes amylase, lipase, and protease to break down the complex carbohydrates, fats, proteins, respectively, that are deficient in EPI patients and that causes poor absorption of essential nutrients (thereby often leading to malnutrition, impaired growth, and reduced survival). OOPD’s decision to revoke the Altus designation comes less than one year before the date FDA established in 2004 requiring the submission of NDAs for PEPs for EPI.  In addition, OOPD’s decision avoids the possibility that TheraCLEC, if it were the first product to obtain FDA approval with orphan drug designation, would be granted seven years of exclusivity, during which FDA could not approve an application for the “same drug” for EPI, absent a showing of “clinical superiority.” 

PEPs have been marketed in the United States for EPI since before the enactment of the FDC Act in 1938.  In April 2004, FDA published a Federal Register notice announcing that all PEPs are “new drugs” under the FDC Act, and that sponsors of currently marketed PEPs must submit and obtain approval of an NDA by April 28, 2008, or be subject to FDA regulatory action.  FDA simultaneously published a guidance document to assist sponsors in submitting NDAs for their PEPs.  With regard to patient needs, FDA’s Federal Register notice states:

[T]here is a need for a range of products to remain available for patient use.  The dosage requirements of patients vary, and the appropriate daily dose of pancreatic enzyme supplements must be individualized and adjusted when clinically indicated.  Furthermore, physicians have identified and stabilized their patients on currently available products with different ratios of lipase, protease, and amylase that meet the patients’ needs.  Thus, to meet the dosing requirements and to maintain compliance with treatment, pancreatic supplements are needed with varied concentrations of lipase, protease, and amylase. 

This statement indicates that FDA anticipates the submission of multiple applications for different drugs to meet the varied needs of EPI patients.  By permitting a single applicant with orphan drug exclusivity to monopolize the PEP/EPI market, however, FDA would be unable to meet its stated public health need for “a range of [PEPs].”  FDA’s decision to revoke the Altus designation removes this impediment. 

Presumably the next exclusivity battle over PEPs will concern whether each PEP is a new chemical entity eligible for 5-year exclusivity or whether 3-year “new use” exclusivity applies.  An FDA determination that all PEPs are different and eligible for 5-year exclusivity is arguably consistent with recent FDA policy conferring 5-year exclusivity “to products about which the Agency has insufficient information to know whether they contain a previously approved active moiety.”  Moreover, FDA has indicated (pages 15-21) that such a policy might be applicable to PEPs.