Executive Summary

ORTHO BIOTECH's LEUSTATIN FOR HAIRY CELL LEUKEMIA now generally available following FDA's Feb. 26 approval of the drug as a first-line treatment for the rare cancer. Leustatin (cladribine, formerly called 2CdA) is priced between $2,085 and $2,800 for the single, seven-day I.V. infusion, with the price varying due to patient size and channel of distribution. For example, the price of a 10 mg vial to the Federal Supply Schedule (after rebate) is $297.92 while the price to wholesalers is $400 per vial. The infusion rate is .09 mg/kg/day of cladribine. Hairy cell leukemia currently affects about 3,000 people, mostly men over the age of 50, and has about 600 new cases reported each year. Leustatin, an orphan drug, has been available as an NCI Group C/Treatment IND drug since March 1992. Ortho will also provide special financial reimbursement and assistance to qualified patients and their physicians. Leustatin is the third drug approved for hairy cell leukemia. Alpha interferon (Schering-Plough's Intron-A and Hoffmann-La Roche's Roferon-A) was approved for the indication in 1986. Warner-Lambert's Nipent (pentostatin) was approved as a second- line therapy in October 1991. FDA's Oncology Drugs Advisory Committee recommended Nipent as a first-line therapy for the indication on March 1 (see following T&G). FDA Commissioner Kessler noted in a March 2 FDA statement on Leustatin's approval that the drug's single treatment dosing schedule "represents a significant advance" in the treatment of hairy cell leukemia. Alpha interferon therapy for hairy cell leukemia is 3 mil. IU daily over six to 24 weeks; Nipent is currently indicated for dosing of 4 mg/m once a week for 24 weeks. Side effects most frequently seen with Leustatin, according to approved labeling, are fever, fatigue and neutropenia in the first two months after treatment. Since the drug is a one-time therapy, it often avoids side effects seen with multi-course cancer therapies, such as hair loss, nausea, vomiting, headaches and rashes, FDA noted. Labeling states that from day 15 to the last follow-up visit, adverse events reported in 5% or more patients were fatigue (11%), rash (10%), headache and cough (7% each) and malaise (5%). Approved labeling states that 89% of patients in the intent- to-treat group in the clinical trials showed complete or partial remissions of their cancers for eight to 25 months. The NDA was based on two open-label clinical trials of 123 patients, of whom 106 were evaluable. In the studies, 60% of patients had not received prior chemotherapy or had had their spleens removed as the only treatment, while the remaining 40% received Leustatin as a second-line therapy after having undergone chemo. The company also conducted a retrospective, blinded evaluation of bone marrow biopsies collected in the trials. As a condition of approval, Ortho Biotech will follow up the duration of response seen in the patients who participated in the NDA clinical trials for a period of three years and provide FDA with annual data from other trials using Leustatin for other lymphoproliferative disorders, the approval letter states. The NDA submission included data on patients through April 30, 1991, and the most recent update is from June 1992. Ortho noted in a March 2 press release that through the course of the updates, fewer than 6% of evaluable patients have had relapses. The approval of Leustatin comes approximately eight-and-one- half months after FDA's Oncology Drugs Advisory Committee recommended the product for approval in June 1992 ("The Pink Sheet" June 22, 1992, p. 6) and about 15 months after the NDA (20- 229) was filed by R.W. Johnson in December 1991. The U.S. approval is the first for cladribine. The drug was synthesized by Scripps in 1981; R.W. Johnson assumed responsibility for its development in February 1991.