Alza Expects Doxil-Hycamtin Ovarian Cancer Study Results To Drive Sales

Alza expects interim results from a Phase III trial comparing its liposomal doxorubicin product Doxil with SmithKline Beecham's Hycamtin (topotecan) in ovarian cancer will accelerate Doxil sales. The results will be presented at the American Society of Clinical Oncology meeting in New Orleans May 20.

"We are looking for a major expansion of Doxil sales related to the presentation at ASCO," Alza Group VP Sam Saks, MD, said during an April 18 conference call. "This is really going to extend our ovarian cancer data and give direct comparison data to topotecan which is our major competitor in this area."

"We will see growth as a result of that data, and you can count on it," Alza Urology Business Unit VP Jay Shepard added.

Alza plans to file a supplemental NDA based on the data.

The interim analysis of the Phase III trial evaluates the safety and efficacy of Doxil versus topotecan in the treatment of patients with relapsed ovarian cancer following the failure of first-line platinum-based therapy, with time-to-progression as the primary endpoint and survival, response rate and safety as secondary endpoints.

In the study, patients received either 50 mg/m2 of Doxil over one hour every four weeks or topotecan 1.5 mg/m2 per day for five days every three weeks. Enrollment for the trial has been completed, the company said.

The 237-patient interim analysis showed a median time to progression of 22.4 weeks for patients on the Doxil arm versus 20.4 weeks for those on topotecan.

Overall survival was 66 weeks for Doxil patients compared to 56.3 weeks for topotecan. A confirmed objective response rate was recorded in 20.3% of patients on the Doxil arm and in 16.8% of patients on topotecan.

Out of the 58 patients who were platinum-refractory in the Doxil arm, 12.1% recorded confirmed objective response rates compared to 6.8% of 59 platinum-refractory patients receiving topotecan.

There were no treatment-related deaths on Doxil versus two with topotecan. Palmar-plantar erythrodysesthesia was the most common adverse event with Doxil, occurring in 25% of patients compared to none of the topotecan patients.

Topotecan was associated with grade 3/4 neutropenia in 71% of patients versus 12% of Doxil patients. Anemia and thrombocytopenia were also higher for topotecan compared to Doxil (33% vs. 5% and 35% vs. 1%, respectively). Alopecia occurred in 8% of topotecan patients versus none of the Doxil patients.

Alza is also planning Phase III trials of Doxil in the treatment of multiple myeloma. Breast cancer trials with the liposomal therapy are ongoing. Doxil is currently used off-label for the treatment of breast cancer, the company noted.

Affiliates of Schering-Plough market Doxil in Europe as Caelyx. Schering-Plough has filed an application in Europe for an ovarian cancer indication for Caelyx, Alza's March 29 SEC filing states.

Doxil recorded sales of $13 mil. in the quarter ending March 31, down from $14.3 mil. in the first quarter of 1999. Doxil sales were affected by Y2K-related wholesaler stockpiling, which was cleared in January and February, the firm said.

During an analysts meeting in February, the company said that it anticipated a 30% growth this year in Doxil sales. "We talked in the February meeting about growing the product by 30% plus 2000 over 1999, and I think that is the best guidance we can give at this point," Saks said.

Sales for Alza's urinary incontinence treatment Ditropan XL (oxybutinin) were up nearly 50% to $32.8 mil. for first quarter 2000 compared to $22 mil. during the same quarter last year.

Ditropan XL sales are expected grow to $140 mil. this year, the company said, constituting a third of the $450 mil. targeted for overall Alza-marketed product sales.

Alza hopes to complete a study comparing Ditropan XL 10 mg to a 2 mg dose of Pharmacia's Detrol (tolterodine) in 2000. The OBJECT trial began in March. European approval for Ditropan XL, sought by Sanofi-Synthelabo, is expected this summer and a market launch in the UK is expected later this year, Alza said.