On September 29, 2015 OXiGENE, Inc. (Nasdaq:OXGN), a biopharmaceutical company developing novel therapies for treatment of cancer, reported its plans for the further advancement of its lead investigational drug, CA4P (combretastatin A4 phosphate, or fosbretabulin) (Press release, OXiGENE, SEP 29, 2015, View Source [SID:1234507610]). This follows a thorough evaluation of the company’s pipeline opportunities.

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OXiGENE’s advancement plans include two phase 2/3 clinical trials evaluating whether CA4P improves the current standard-of-care in patients who have failed to respond to initial treatment. Both trials planned by the company are designed as two stage, phase 2/3 studies. The first stage of each trial would be a randomized, investigator-blinded, placebo-controlled study with up to 80 patients. The second stage of each trial would be a large, double-blind, placebo-controlled, confirmatory phase 3 study, the start of which would be triggered by a demonstration of efficacy in the first stage. Each trial is designed so that a particularly robust efficacy signal in the first stage would accelerate the timing of the transition into the larger second stage phase 3 portion.

Ovarian cancer

The first clinical trial OXiGENE plans to initiate will be in platinum-resistant ovarian cancer, with the goal of determining whether the addition of CA4P to the standard-of-care (chemotherapy plus Avastin (bevacizumab)) improves patient outcomes. Patients would be randomized on a 1:1 basis to receive either the current standard-of-care or the current standard-of-care plus CA4P. The primary endpoint will be progression-free survival (PFS). The company expects to initiate the trial in the first half of 2016.

The proposed phase 2/3 trial is based on the results of the recent GOG186I study in which the anti-vascular combination of CA4P and Avastin showed statistically significant improvements in PFS compared to Avastin alone. The benefits appeared to be particularly robust in patients with platinum-resistant disease where a post-hoc subgroup analysis of the study showed that patients who had platinum-resistant disease had a median PFS of 6.7 months when treated with Avastin and CA4P compared to 3.4 months for those receiving Avastin alone.

"In analyzing the various clinical trials that OXiGENE has conducted over the years, CA4P, also known as fosbretabulin, has repeatedly shown a positive effect in the treatment of solid tumors," stated William D. Schwieterman, M.D., OXiGENE’s President and CEO. "However, the effect of CA4P has been markedly stronger when it is given in combination with an anti-VEGF agent such as Avastin, since the two drugs attack a tumor’s blood-flow in a complementary manner. The most striking example of this that we have seen was in platinum-resistant patients in the most recent ovarian cancer trial, and we aim to build upon these positive results in our planned trial by including the chemotherapy that most patients receive."

Given the greater potential commercial value of the currently proposed study, OXiGENE no longer plans to study or submit a Special Protocol Assessment for the combination of CA4P and Avastin without chemotherapy.

In the U.S., approximately 22,000 women are diagnosed with ovarian cancer each year, of which 4,300 are resistant to platinum-based therapies.

Glioblastoma multiforme

The second phase 2/3 clinical trial OXiGENE plans to initiate will be in glioblastoma multiforme (GBM) patients who have failed first-line chemotherapy treatment, with the goal of determining whether CA4P improves upon the current standard of care, which is treatment with Avastin alone. Patients will be randomized on a 1:1 basis to receive either Avastin or Avastin plus CA4P. The primary endpoint will be PFS. The company expects to initiate the trial in the second half of 2016.

"The combination of CA4P and Avastin, without any chemotherapy, is the same treatment regimen that ovarian cancer patients recently received in the GOG study. Based on the highly vascular nature of tumors in GBM, similar to ovarian cancer tumors, we believe that CA4P can have a potentially meaningful effect in this indication," continued Dr. Schwieterman. "The medical need is unquestionable, and I believe that this unmet need combined with the dearth of other GBM treatment options and competing clinical trials will provide us the shortest potential path towards approval."

In the U.S., approximately 11,000 patients are diagnosed with glioblastoma multiforme each year, of which 6,000 are considered recurrent.

Other programs continue on track

The company also announced that it will continue to evaluate CA4P in two ongoing studies, which are:

A phase 1b/2 clinical trial in combination with VOTRIENT (pazopanib) in advanced recurrent ovarian cancer. Initial data from the dose escalation portion is expected to be presented at the European Society of Gynaecological Oncology conference being held October 24-27, 2015.
A phase 2 clinical trial as a single agent in patients with gastrointestinal and pancreatic neuroendocrine tumors, with interim data expected to be available approximately year-end 2015.
OXiGENE’s other investigational drug, OXi4503, is being studied in a phase 1 clinical trial in patients with Acute Myeloid Leukemia (AML), and the company is in the process of expanding the trial to include additional investigator sites.

Conference Call

Members of OXiGENE’s management team will host a webcast and conference call tomorrow, September 30, 2015, at 9:00 a.m. EDT (6:00 a.m. PDT) to discuss OXiGENE’s CA4P development plans.

To listen to a live or an archived version of the audio webcast, please log on to the Company’s website, www.oxigene.com. Under the "Investors & Media" tab, select the link to "Events and Presentations." OXiGENE’s conference call can also be heard live by dialing (888) 841-3431 in the United States and Canada, or +1 (678) 809-1060 for international callers, five minutes prior to the beginning of the call. The conference ID is 51228074.

On September 29, 2015 GTx, Inc. (Nasdaq: GTXI) reported the enrollment of the first patient into its Phase 2 clinical trial of enobosarm (GTx-024) to treat women with advanced, estrogen receptor positive (ER+), androgen receptor positive (AR+) breast cancer (Press release, GTx, SEP 29, 2015, View Source [SID:1234507609]). Enobosarm, a selective androgen receptor modulator (SARM), is the Company’s lead product candidate.

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"Additional endocrine directed therapies are needed for the treatment of estrogen receptor positive breast cancer as many women who respond to hormonally directed therapy will continue to demonstrate response with subsequent hormonal manipulation," said Robert J. Wills, Ph.D., Executive Chairman of GTx. "We believe that enobosarm may provide a new hormonal approach for the treatment of estrogen receptor positive breast cancer and may delay the need for chemotherapy in these women."

The open-label, multi-center, multinational Phase 2 clinical trial (NCT02463032) will assess the efficacy and safety of orally administered enobosarm in up to 88 evaluable patients with metastatic or locally advanced, ER+/AR+ breast cancer. Patients will receive either enobosarm 9 mg or 18 mg given daily for up to 24 months. The initial stage of evaluation will be assessed among the first 18 evaluable patients for each dosing arm. If at least 3 of 18 patients achieve clinical benefit at week 24, then the trial will proceed to the second stage of enrollment for that dosing arm to assess clinical benefit in a total of 44 evaluable patients per arm. Clinical benefit is defined as a complete response, partial response, or stable disease, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) at 24 weeks. The lead investigator for the trial is Dr. Beth Overmoyer from the Dana Farber Cancer Institute and the Harvard Medical School.

About enobosarm

Enobosarm, a selective androgen receptor modulator (SARM), has been evaluated in 23 completed or ongoing clinical trials enrolling over 1,500 subjects at doses ranging from 0.1 mg to 100 mg. At all evaluated dose levels, enobosarm was observed to be generally safe and well tolerated.

Most recently, enobosarm 9 mg has been tested in a Phase 2, proof of concept clinical trial of 22 postmenopausal women with ER+ metastatic breast cancer who have previously responded to endocrine therapy. Seventeen of the 22 patients were confirmed to be AR+. Six of these 17 patients demonstrated clinical benefit at six months. Seven patients in total (one patient with indeterminate AR status) achieved clinical benefit at six months. The results also demonstrated that, after a median duration on study of 81 days, 41 percent of all patients (9/22) achieved clinical benefit as best response and also had increased PSA which appears to be an indicator of AR activity. Enobosarm was well tolerated. The most common adverse events reported were pain, fatigue, nausea, hot flash/night sweats, and arthralgia.

About ER+/AR+ Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women, and one in eight women will develop invasive breast cancer in their lifetime. In 2012, 1.7 million women were diagnosed with breast cancer, and there were 6.3 million women alive who had been diagnosed with breast cancer in the previous five years. Clinical assessment of breast cancer provides for routine characterization of receptor status including the presence or absence of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in the tumor tissue. Receptor status is used to assess metastatic potential as well as to guide treatment decisions. The majority of breast cancers are considered hormone receptor positive (expressing ER or progesterone receptor). Approximately 70 percent of women in the U.S. with breast cancer have ER+ tumors, and 75 to 90 percent of these cancers are also AR+.

Estrogen promotes the growth of breast cancers that are hormone receptor positive. Therefore, treatment is directed at blocking the effects of estrogen on the breast cancer either through blocking the estrogen receptor or minimizing the production of estrogen. This endocrine therapy is the cornerstone of treatment for the majority of women with hormone receptor positive advanced breast cancer and is the preferred initial treatment over alternative approaches such as chemotherapy, due to its efficacy and favorable safety profile. Patients who respond to one endocrine therapy are likely to respond to subsequent hormonal therapies. Therefore, the standard of care for women with hormone receptor positive breast cancer typically involves the sequencing of endocrine agents until intolerance or development of resistance occurs, or metastatic progression necessitates a transition to chemotherapy.

Enobosarm may offer an alternate hormonal approach for the treatment of endocrine sensitive advanced breast cancer prior to the introduction of chemotherapy.

On September 29, 2015 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental New Drug Application (sNDA) for Eisai’s in-house developed anticancer agent Halaven (eribulin mesylate) as a treatment for soft tissue sarcoma, and granted the sNDA Priority Review status (Press release, Eisai, SEP 29, 2015, View Source [SID:1234507599]).

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The FDA’s Priority Review designation is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. Through this process, the FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date (proposed review deadline) of January 29, 2016, six months after the sNDA was submitted.

Eisai submitted applications seeking approval for the additional indication of soft tissue sarcoma in the United States and Europe (EU) respectively on July 29, 2015, and in Japan on July 30, 2015.

Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (fat, muscle, nerves, fibrous tissues and blood vessels) in the body. Approximately 12,000 patients in the United States and 29,000 patients in Europe are diagnosed with soft tissue sarcoma each year. According to a patient survey conducted by the MHLW, there are approximately 4,000 patients with soft tissue sarcoma in Japan. Meanwhile, Halaven has been designated as an orphan drug for the treatment of soft tissue sarcoma in the United States and Japan.

Halaven is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. It was first approved for the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved in approximately 60 countries including Japan and countries in Europe, the Americas and Asia.

Eisai remains committed to providing further clinical evidence for Halaven aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.