MERCK'S CUPRID ORPHAN DRUG FOR WILSON'S DISEASE RESULTS FROM FDA REQUEST

Merck's Cuprid for Wilson's Disease is an orphan product developed by the company in response to specific requests from FDA, HHS Secty. Heckler noted at a Nov. 26 press conference to announce approval of the product. Heckler declared that the development of Cuprid (trientine HCl or trien) was undertaken by Merck "at the urging of FDA, the Foundation for the Study of Wilson's Disease, and the PMA Commission on Drugs for Rare Diseases," and that the company "agreed to produce the drug under FDA's on-going orphan program." Heckler said that in 1982 "FDA's Office of Orphan Products Development recognized the potential usefulness of trien for Wilson's disease, and sought a sponsor to develop and test it." In October 1982 Merck notified FDA that it would assume responsibility for the development of Cuprid. The company already markets Cupramine (penicillamine) to which an approximate 10% of the 1,000 Americans diagnosed as having Wilson's disease are intolerant. According to approved labeling, Cuprid "is indicated in the treatment of patients with Wilson's disease who are intolerant of penicillamine." Merck VP-Clinical Research Marvin Jaffe, MD, stated that "the major incentive" for developing the drug was knowing from the start "what the requirements for approval would be; so we had knowledge before we accepted responsibility for the drug of who would do what." Jaffe noted that "in this case, the Natl. Institutes of Health agreed to do some of the long-term preclinical safety studies, which is the very arduous, time consuming and expensive part of any new drug development process. And we agreed to do specific clinical programs and the gathering of clinical data to document the stability and purity of the compound." Jaffe noted that the company will not be able to take advantage of any of the financial benefits of the Orphan Drug Act because Cuprid was developed prior to the law's passage. Jaffe said that trien will "cost approximately $100 per month to the patient . . . and that is about 20% more" than Merck's Cupramine costs. The estimated patient population for Cuprid is 100. Cuprid labeling notes that the drug "is effective as a cupriuretic agent in patients with Wilson's disease although on a molar basis it appears to be less potent or less effective than penicillamine." With regard to adverse effects, the labeling states that in patients treated for Wilson's disease, iron deficiency and one case of systemic lupus erythematosus were reported. The one case of lupus was a recurrence of the symptoms that had "appeared originally during therapy with penicillamine." The labeling also notes that "unlike penicillamine, Cuprid is not recommended in cystinuria or rheumatoid arthritis." Merck stated in a press release that its other "contributions to public service medicine include the anti-cancer agents Elspar (lymphocytic leukemia) and Cosmegen (Wilms' Tumor), Desmer, for a rare form of hypertension associated with adrenal tumors, as well as the antivenin for black widow bite and Indocin IV, a new public service drug for the treatment of patent ductus arteriosus, a heart condition which threatens the lives of prematurely born infants."