EPO ORPHAN POPULATION IS BASED ON NUMBER OF DIAGNOSED PATIENTS

EPO ORPHAN POPULATION IS BASED ON NUMBER OF DIAGNOSED PATIENTS rather than a theoretical number of patients suffering from a disease according to FDA's reading of the Orphan Drug Act, the agency told Chugai-Upjohn in a Jan. 11 letter. The letter denies company petitions seeking to revoke orphan exclusively for Amgen's Epogen (Epoetin alfa) for chronic renal failure and anemia and to allow marketing of Chugai-Upjohn's EPO product Marogen. "FDA's position of considering only diagnosed patients is entirely consistent with Congress' purpose in enacting the Orphan Drug Act," the letter states. The agency maintained that the "relevant patient population of CRF sufferers consists of those who could benefit from the drug EPO (i.e. diagnosed symptomatic patients)." FDA said that if it were to use the "theoretical prevalence of a disease or condition rather than estimates of those who would likely benefit from a drug," it could "be put in the anomalous position of presuming some drugs not to be orphans when in fact they will only be used by a small number of people." The FDA letter responds to arguments put forth in petitions submitted to the agency by Chugai-Upjohn in November and December 1989, and in January 1990. The petitions argue that Epogen's orphan exclusivity should be revoked because: the CRF population exceeds 200,000; end-stage renal disease should never have been designated an orphan indication; EPO treatment of CRF anemia therefore cannot be accorded orphan exclusivity; the Orphan Drug Act was not intended to conflict with patent laws; and Marogen is a structurally different product than Epogen. FDA's own analyses in 1986, 1987, 1989 and 1990 show that the diagnosed patient population for CRF is consistently under 200,000, the agency asserted. Although the patient population has been increasing, FDA maintained that "it has been less than 200,000 at all possibly relevant times." When Amgen sought orphan designation, FDA set the CRF population in the U.S. at 191,000, with 116,000 qualifying for EPO treatment. In August 1990, FDA said that, based on information from the Health Care Financing Administration, it revised its estimate of CRF patients requiring EPO treatment to 160,600. Data submitted by Chugai-Upjohn "has not persuaded FDA that this conclusion is wrong," the letter states. In its January petition, Chugai-Upjohn cited a study conducted by the Arlington, Va.-based Degge Group Ltd. which estimated the CRF population at more than 600,000 ("The Pink Sheet" Feb. 12, p. 9). FDA analysis of the Degge report "revealed major flaws . . . and raised serious questions regarding the validity of the estimates." As a result, the letter says, "no valid conclusions can be drawn from them." In response to Chugai-Upjohn's second argument, FDA said that end-stage renal disease was an appropriate designation in 1986 because the Medicare statute uses the term "as a specific entitlement determination." FDA added that it finds no significant differences between ESRD and CRF. "They are pathophysiologically the same disease, [and] the same dosage and treatment regimen of EPO apply to treatment for ESRD and CRF." "Making a distinction between dialysis patients and non- dialysis patients can be confusing to physicians in that some patients are on dialysis sometimes and off dialysis other times," the agency said. "Patients who move on and/or off dialysis should not be made to change the source of their drug therapy," FDA added. Such confusion could pose a problem for Ortho, which recently received approval to market Amgen's Epoetin alfa under the tradename Procrit for the non-dialysis anemia market ("The Pink Sheet" Jan. 7, p. 5). "In retrospect," FDA acknowledges in the petition denial, that "it would have been preferable for Amgen to have requested to amend its orphan drug designation prior to the June 1, 1989 licensure to make the orphan designation identical to the soon-to- be-approved indication." However, the letter notes that FDA "considers this failure on Amgen's part to be a 'harmless error'." Chugai-Upjohn's assertion that the agency's administration of the Orphan Drug Act conflicts with patent laws is "at best premature," FDA said, since the patent dispute is still ongoing. "We understand that ongoing litigation in Massachusetts and elsewhere may not finally decide the parties' patent rights for years to come, unless there is a settlement before then," the agency's letter states. Amgen, Chugai-Upjohn and its licensing partner Genetics Institute are awaiting a D.C. circuit court ruling on a December 1989 Boston federal court decision upholding the validity of certain portions of both Amgen's and Genetics Institute's EPO patents that could force the companies into a cross-licensing agreement ("The Pink Sheet" Sept. 10, In Brief). At the end of the FDA denial letter to Chugai-Upjohn, Associate Commissioner for Regulatory Affairs Ronald Chesemore told the company that its PLA for EPO "will be approved only if FDA determines that it is not the same drug as Amgen's EPO for purposes of the Orphan Drug Act." FDA's Blood Products Advisory Committee was to have considered that issue at its June 1990 meeting; however, the meeting was postponed and the topic has not been rescheduled for another committee meeting.