DuPont Merck/Cytogen Quadramet bone pain radiotherapeutic to be launched in mid-May.

DUPONT MERCK/CYTOGEN QUADRAMET LAUNCH PLANNED FOR MID-MAY following FDA approval of the radiopharmaceutical for bone pain treatment March 28. The planned launch of samarium Sm 153 lexidronam depends on several factors, including regulatory approval from the Nuclear Regulatory Commission, DuPont Merck said. DuPont Merck estimates that the cost of a Quadramet procedure will be $2,000-$4,000 per treatment. Princeton, N.J.-based Cytogen acquired Quadramet from Dow and licensed U.S. manufacturing and marketing rights to DuPont Merck. Cytogen retains co-promotion rights in the U.S.

DuPont Merck plans to support the launch with advertising in The Journal of Urology, The Journal of Clinical Oncology, and The Journal of Nuclear Medicine. The ads, which will debut in June, were developed by Integrated Communications (Parsippany, N.J.). Launch materials for the drug will also include patient brochures to be distributed by physicians. DuPont Merck plans to support the launch with 120 sales reps.

Abstracts on Quadramet research will be presented at the American Urology Association conference in April, the Oncologic Nursing Society meeting in May and the Nuclear Medicine convention in June. DuPont Merck also will have a chance to introduce the product at the American Society of Clinical Oncology meeting in May.

Samarium is approved "for relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan." The indication does not limit Quadramet to specific cancers, although clinical trials focused primarily on prostate cancer patients.

Quadramet was evaluated in 580 patients, 270 of whom were enrolled in placebo-controlled pivotal studies lasting four weeks. Patients receiving 1 mCi/kg of Quadramet showed statistically significantly lower scores on a visual analogue pain scale after four weeks in both pivotal trials, labeling states. In one study, a significant difference was first seen after two weeks; in the second trial, the difference was seen at three weeks.

Fifty-four percent of patients on drug in one study showed a decrease in pain scores v. 25% of placebo patients. In the second trial, 48% of Quadramet patients v. 22% of placebo patients experienced a decrease in pain.

The pivotal trials also assessed differences in supplemental opioid use. In one study, patients received no instruction on use of pain medication, and no significant difference was seen between drug and placebo. In the second study, patients were instructed to adjust pain medication as needed and a significant difference between the two groups was seen. By week four, samarium patients who had received medication instruction had a weekly mean analgesic use of 76.8 morphine equivalent units. Placebo patients from the same group had a mean analgesic use of 106.3 morphine equivalent units.

Phase IV commitments by Cytogen include studies of patients with renal insufficiency, pediatric studies, studies enrolling patients with predominantly osteolithic bone lesions and studies of the relationship between samarium use and the number of metastatic lesions. Cytogen is also conducting Phase I trials for treatment of osteogenic sarcoma and for severe rheumatoid arthritis as well as Phase I/II trials for treatment of prostate cancer.

Quadramet labeling carries a warning about bone marrow suppression. "In clinical trials, white blood cell counts and platelet counts decreased to a nadir of approximately 40% to 50% of baseline in 123 (95%) of patients within three to five weeks after Quadramet, and tended to return to pretreatment levels by eight weeks," labeling states.

The most common adverse events occurring more frequently in patients receiving samarium than in patients on placebo were thrombocytopenia (69.3% v. 8.9%), leukopenia (59.3% v. 6.7%), hemoglobin decrease (40.7% v. 23.3%), infection (17.1% v. 11.1%) and bleeding manifestations (16.1% v. 8.9%).

Quadramet was approved with a "1S" rating, designating a new molecular entity given a standard review by the agency. Cytogen submitted the NDA (20-570) on June 12, 1995, followed by numerous supplements. Cytogen met with the agency on the application three times, most recently on Jan. 23. The user fee goal date for the application was March 30, 1997, FDA said. Cytogen has previously received approvals for two imaging agents, ProstaScint and OncoScint.