Bryan Sclerosol for prevention of recurrent malignant pleural effusion to be launched by March.

BRYAN SCLEROSOL FOR MALIGNANT PLEURAL EFFUSIONS SET FOR LAUNCH BY MARCH, the Woburn-Mass.-based company said following FDA approval of the intrapleural aerosol talc product Dec. 24. Sclerosol is indicated for use during thoracoscopy or open thoracotomy "to prevent recurrence of malignant pleural effusions in symptomatic patients."

Sclerosol becomes the second agent to be approved for the indication based on a literature review. Bristol-Myers Squibb's Blenoxane (bleomycin) was approved in February 1996 for treatment of pleural effusions and prevention of recurrent effusions. There are about 175,000 to 180,000 patients who suffer from malignant pleural effusions, Bryan estimates ("The Pink Sheet" April 15, T&G-6).

Bryan indicated that Sclerosol will likely be marketed at a lower cost than Blenoxane. The company will market Sclerosol to pulmonary and cardiothoracic specialists, as well as general surgeons.

The high cost of bleomycin has been cited in literature as a disadvantage to its use for MPE. A study by Pamela Walker-Renard, et al., Medical University of South Carolina, compared the average wholesale prices of various pleurodesis agents in an article that appeared in the Jan. 1, 1994 edition of the Annals of Internal Medicine. The authors found that a 10 g dose of USP talc cost less than $1, compared to $1,104 for a 70 unit dose of bleomycin and $85-$403 for doxycycline. Bristol investigators responded that aerosol talc must be used in an operating room under general anesthesia, and is therefore associated with costs exceeding the cost of one dose of bleomycin.

A three-year study comparing the cost-effectiveness of talc through slurry, Blenoxane and doxycycline by the National Cancer Institute's Eastern Cooperative Oncology Group has begun. The study is looking at number of days spent in the hospital and the need for retreatment and hospital readmission as markers of total treatment cost. The primary efficacy endpoint, time to recurrence, will be evaluated at 30 and 90 days.

The Sclerosol literature-based NDA (20-587) was unanimously recommended for approval by FDA's Oncologic Drugs Advisory Committee in December 1995 ("The Pink Sheet" Dec. 18, 1995, T&G-6). Sclerosol was "approvable" twice, on Aug. 9, 1996 and Oct. 27. Bryan first submitted its application in August 1995 in response to a letter sent by FDA to all talc distributors in March 1994 requesting literature-based NDAs. Bryan said it resubmitted the application on Nov. 13, 1997 to incorporate changes pertaining to Phase IV requirements. The user fee deadline for the compound was May 16, 1998. FDA designated Sclerosol a "1P," a new molecular entity receiving a priority review.

Studies from the literature included in labeling show response rates to talc slurry or poudrage of 90% to 100% in evaluable patients compared to response rates of 58% for chest tube drainage, 48% for tetracylcine slurry and 33% bleomycin solution. The response rate to talc in all patients was between 61% to 78%. Duration of response to talc therapy lasted up to 12 months.

Labeling cautions that future diagnostic and therapeutic procedures involving the nemithorax must be considered before administration of Sclerosol, because "sclerosis of the pleural space may preclude subsequent diagnostic procedures of the pleura on the treated side," and "may complicate or preclude future ipsilateral lung resective surgery, including pneumonectomy for transplantation purposes."

Adverse reactions to talc were "difficult to distinguish from the effects of the procedure(s) associated with its administration," but the most common adverse effects were fever and pain, labeling states. The usual dose of Sclerosol is a single dose of 4-8 g delivered intrapleurally from a spray canister containing 4 g talc suspended in 26 g of inert propellant. Manufactured by Hicksville, N.Y.-based Sciarra Laboratories, the drug received a chlorofluorocarbon use exemption on May 21, 1996.