Spectrum Pharmaceuticals Announces Agreement with FDA on the Special Protocol Assessment (SPA) for the Upcoming Apaziquone Phase 3 Trial in Patients with Non-Muscle Invasive Bladder Cancer (NMIBC)

On August 17, 2015 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations and a primary focus in Hematology and Oncology, reported that the company has reached agreement with the U.S. Food and Drug Administration (FDA) on the Special Protocol Assessment (SPA) of the planned Phase 3 clinical trial of its novel, potent pro-drug, apaziquone (Press release, Spectrum Pharmaceuticals, AUG 17, 2015, View Source [SID:1234507284]). This trial will further evaluate the intravesical use of apaziquone for the treatment of patients with non-muscle invasive bladder cancer (NMIBC) as one or two instillations, immediately following transurethral resection of bladder tumor (TURBT).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Spectrum’s agreement with the FDA on the SPA represents a significant milestone for bladder cancer patients," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "The learnings from previous Phase 3 studies and comments from the FDA have been incorporated in the new protocol to improve the chances of success. We look forward to initiating this trial and filing the apaziquone NDA by year-end. This NDA is based on data from the previously completed program that included two Phase 3 studies with a total of 1,615 patients. We believe there continues to be a significant unmet need for these patients, as no drugs have been approved in the U.S. for more than 40 years for the treatment of low-grade NMIBC. Due to the high rate of recurrence, the overall cost of the treatment of bladder cancer in the U.S. is a staggering $3.4 billion annually, most of which is related to direct treatment of the disease. We endeavor to bring this much needed therapy for patients and help reduce overall medical costs at the same time."

In accordance with the SPA, the Phase 3 trial will be a randomized, double-blind, placebo-controlled, multicenter trial that will enroll patients with Ta G1 or G2 NMIBC. The patients will be randomized to receive either one instillation of apaziquone, two instillations of apaziquone, or placebo. The primary endpoint is Time to Recurrence. Since apaziquone is known to be inactivated in presence of blood, the new protocol includes a 30-60 minute waiting period post-TURBT, before apaziquone instillation. Patients that receive two instillations of apaziquone, will receive the second dose approximately two weeks after surgery minimizing the potential for drug inactivation due to bleeding. Further, it is recommended that patients with significant post-operative bleeding not receive apaziquone.

Apaziquone is an anticancer pro-drug that is activated by bio-reductive enzymes that are over-expressed in bladder cancer cells, rendering it into a highly cytotoxic alkylating agent. Spectrum has conducted two multi-center, international Phase 3 trials of a single intravesical instillation of apaziquone (4 mg) into the bladder in the immediate post-operative period after surgical resection of low-grade NMIBC. Pooled data from the two studies (n=1,615) showed a statistically significant treatment effect for the primary study endpoint, 2-Year Recurrence Rates, in favor of apaziquone (p-value = 0.0218) and in a key secondary endpoint, Time to Recurrence (p-value = 0.0096).

About Bladder Cancer

According to the National Cancer Institute, bladder cancer is the fifth most common malignancy in the US with 74,000 new cases of bladder cancer expected in 2015, and currently over 500,000 patients living with the disease. Due to high recurrence rates, intensive surveillance strategies, and expensive annual treatment costs, bladder cancer has the highest per patient costs, and an overall cost estimated at around $3.4 billion. Non-muscle invasive bladder cancer (NMIBC) is a form of bladder cancer that is localized in the surface layers of the bladder and has not invaded or spread to the deeper muscle layer. Approximately 70% of all patients newly diagnosed with bladder cancer have NMIBC. Urologists treat the disease predominantly by transurethral resection of the bladder tumor(s) (TURBT); in the U.S., there are approximately 300,000 TURBT procedures every year to treat bladder cancer. Because of the high recurrence rates, both professional urology associations and NCCN Guidelines recommend instillation of a cytotoxic agent following TURBT for NMIBC, although in the U.S., there are no FDA-approved agents for this indication.