On August 14, 2017 Spectrum Pharmaceuticals, Inc. (NasdaqGS:SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported the Company has enrolled the first patient in a Phase 3 trial of Qapzola, a potent tumor-activated drug being investigated for low and intermediate risk non-muscle invasive bladder cancer (Press release, Spectrum Pharmaceuticals, AUG 14, 2017, View Source [SID1234520209]). Under the SPA, this trial will evaluate the intravesical use of Qapzola in patients with non-muscle invasive bladder cancer (NMIBC), as a single instillation 60 ± 30 minutes, following transurethral resection of the bladder tumor (TURBT).

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"Qapzola is being developed for low-to-intermediate risk non-muscle invasive bladder cancer for which there are no approved drugs in the 21st century," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "This is a novel drug that becomes cytotoxic only when it encounters hypoxic tumor such as non-muscle invasive bladder cancer. Bladder tumors are rich in DT-diaphorase, an enzyme that converts Qapzola into an alkylating agent that leads to cell death. One of the key challenges in the treatment of bladder cancer is a significantly high recurrence rate which leads to exorbitant costs and high patient morbidity. It is estimated that the cost of treatment of this disease will surpass $5 billion by 2020. The design of the current trial incorporates learnings from previous studies, feedback from leading KOL’s as well as from the FDA. I believe, Spectrum’s pipeline has never been as exciting as it is today. In addition to aggressive development of Qapzola, we expect to file a registration application (BLA) with the FDA for Rolontis in 2018 and we are very excited with the early data we are seeing with Poziotinib, our novel irreversible tyrosine kinase inhibitor."

In accordance with the SPA, the Phase 3 trial is a randomized, double-blind, placebo-controlled, multi-center trial that will enroll patients with low and intermediate risk NMIBC as per the American Urology Association (AUA) Guidelines. The new study design with a reduced sample size from 1557 to about 425 patients will significantly shorten the duration of this trial. The protocol includes a single instillation of Qapzola 60 ± 30 minute post-TURBT, to avoid inactivation of Qapzola by blood that is present after surgery. The patients will be randomized 2:1 to receive either 8 mg instillation of Qapzola or placebo post-TURBT. Following one instillation of study drug and a safety follow-up at Day 35, subsequent follow up visits will be conducted until tumor recurrence or end of study, whichever occurs first. The primary endpoint for this trial is Time to Recurrence.

About Bladder Cancer

According to the National Cancer Institute, bladder cancer is the fifth most common malignancy in the US with 79,030 new cases of bladder cancer expected in 2017, 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 lifetime cost per patient of all cancers, 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.

About Special Protocol Assessments

A Special Protocol Assessment is a written agreement between a Sponsor and the U.S. Food and Drug Administration on the design, execution and analysis for a clinical trial that may form the basis of a new drug application, or NDA. Final marketing approval depends upon the efficacy results, safety profile and an evaluation of the risk/benefit of treatment demonstrated in the Phase 3 clinical program.

On August 14, 2017 GTx, Inc. (Nasdaq: GTXI) reported financial results for the second quarter of 2017 and highlighted recent accomplishments and upcoming milestones (Press release, GTx, AUG 14, 2017, View Source [SID1234520208]).

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During the quarter, GTx announced positive preliminary clinical data from an ongoing, open-label, Phase 2 proof-of-concept clinical trial of enobosarm in postmenopausal women with stress urinary incontinence (SUI). The Company also has continued to advance two additional R&D programs which are outlined below.

"We are impressed with the positive results in the first seven patients dosed in the SUI study. Stress urinary incontinence is a serious and often embarrassing condition which can have a significant negative impact on a patient’s quality of life. We are focused on potentially addressing this prevalent condition with a first-in-class, orally-administered therapy," said Robert J. Wills, Ph.D., Executive Chairman of GTx.

Corporate Highlights and Anticipated Milestones

Enobosarm in Stress Urinary Incontinence: The Company has an ongoing Phase 2 proof-of-concept clinical trial of enobosarm 3 mg in postmenopausal women with SUI. This open-label, non-placebo controlled proof-of-concept clinical trial is the first of its kind to evaluate an orally-administered selective androgen receptor modulator (SARM) for SUI.

In June 2017, the Company announced preliminary results from the first seven women in the ongoing trial, in which all of the women treated with enobosarm showed a clinically significant reduction (50 percent or greater) in incontinence episodes per day, as measured by mean stress leaks from baseline to week 12 of the trial.
Mean stress leaks decreased by 80.9 percent overall; stress leaks dropped from 5.7 to 1.1 leaks per day.
These results, as well as data from additional patients, will be presented at the International Continence Society (ICS) annual meeting in September 2017. The results from the first seven patients can be found here.
Encouraged by the results to date from its SUI proof-of-concept clinical trial, the Company is planning to initiate in the second half of 2017 a randomized, double-blinded Phase 2 clinical trial to assess the efficacy and safety of two doses of enobosarm (3 mg and 1 mg) per day against placebo with the expectation that top-line data from this trial will be available by the end of 2018.
Enobosarm in Breast Cancer:

The Company has an ongoing Phase 2 clinical trial of enobosarm in estrogen receptor positive (ER+) and androgen receptor positive (AR+) breast cancer.

The Company reported in November 2016 that the pre-specified threshold for success of the trial was already attained in the 9 mg cohort, with nine patients achieving a clinical benefit response (CBR) at 24 weeks among the first 22 evaluable patients in that cohort.
CBR is defined as a complete response, partial response or stable disease, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) at 24 weeks of treatment.
The Phase 2 clinical trial is fully enrolled with at least 44 evaluable patients enrolled in each of the 9 mg and 18 mg cohorts of the trial, and the Company expects to report top-line results in the third quarter of 2017.
The independent Safety Monitoring Committee established to monitor the safety of this clinical trial met on August 11, 2017, and recommended that the trial continue as planned.
The Company’s Phase 2 clinical trial of enobosarm in AR+ triple negative breast cancer completed the first stage of the two stage trial. Since there was insufficient CBR demonstrated among patients enrolled in the first stage of the trial, the Company has determined that the second and final stage of the trial will not continue.

One patient who achieved stable disease remains on study for approximately 10 months from the initiation of treatment.
Enobosarm in Duchenne muscular dystrophy (DMD): The Company has conducted preclinical studies evaluating SARMs in DMD. In preclinical models of DMD, GTx SARMs have increased body weight, lean mass and physical function.

The Company is pursuing a potential strategic collaboration with biopharma companies experienced in orphan drug development to continue the development of a SARM for the treatment of DMD.
SARDs in Prostate Cancer: The Company has a Selective Androgen Receptor Degrader (SARD) preclinical program to evaluate its novel SARD technology in castration-resistant prostate cancer (CRPC).

The Company has ongoing preclinical studies to select the most appropriate compound to advance into a first-in-human clinical trial.
Second Quarter 2017 Financial Results

As of June 30, 2017, cash and short-term investments were $11.4 million compared to $21.9 million at December 31, 2016. On August 10, 2017, the Company entered into a loan agreement (the "Loan Agreement") with J.R. Hyde, III, the largest shareholder of the Company and its Lead Director of its Board of Directors, and The Pyramid Peak Foundation, another large shareholder of the Company, (the "Lenders") for the Lenders to make available to the Company from time to time during the term of the Loan Agreement up to $15 million at an interest rate of 8% per annum (the "Loan"). The term of the Loan Agreement is for a period of nine (9) months and is unsecured. The Lenders have agreed that they will participate in any "qualified" financing (defined as the sale of equity by the Company during the term of the Loan Agreement which equals or exceeds $15 million) at least to the extent of any outstanding indebtedness under the Loan.
Research and development expenses for the quarter ended June 30, 2017 were $4.4 million compared to $4.1 million for the same period of 2016.
General and administrative expenses were $2.0 million for both the quarter ended June 30, 2017 and June 30, 2016.
Net loss for the quarter ended June 30, 2017 was $6.4 million compared to a net loss of $6.1 million for the same period in 2016.
Net loss for the six months ended June 30, 2017 was $12.7 million compared to a net loss of $3.9 million for the same period in 2016. The six months ended June 30, 2016 included a non-cash gain of $8.2 million due to the change in fair value of the Company’s warrant liability, recorded in the first quarter of 2016. During the first quarter of 2016, the Company modified its outstanding warrants with no further adjustment to the fair value of these warrants being required.
GTx had approximately 16 million shares of common stock outstanding as of June 30, 2017. Additionally, there remain warrants outstanding to purchase approximately 6.4 million shares of GTx common stock at an exercise price of $8.50 per share.