|Creating the next generation of cancer treatments
October 27, 2014
Arno Therapeutics Advances Phase I Trial Evaluating Onapristone in Progesterone Receptor Positive Tumors to Expansion Stage
- Phase II dose determined, Anti-tumor activity observed -
FLEMINGTON, NJ - October 27, 2014 - Arno Therapeutics, Inc. (OTCQB: ARNI), a clinical stage biopharmaceutical company focused on the development of oncology therapeutics, today announced that it has advanced its Phase I clinical trial evaluating its lead compound onapristone in women with progesterone receptor expressing tumors to the expansion stage and has now begun enrolling patients at the recommended Phase II dose of 50mg extended release tablets twice daily. This dose has been determined by an independent safety review committee to be safe and is the single agent dose which will be used in future clinical studies. The expansion stage of the Phase I study will include approximately 24 patients and is expected to primarily enroll patients with gynecologic tumors (including endometrial, ovarian and other uterine tumors) who have received fewer prior chemotherapy regimens than the patients enrolled in the dose escalation stage of the study.
Alex Zukiwski, MD, Chief Executive Officer of Arno Therapeutics, remarked, "Identifying the recommended Phase II onapristone dose is an important step forward for our proposed Phase II registration study in women with endometrioid cancer, which is expected to begin enrolling patients next year. The safety profile of onapristone in the dose escalation stage of the Phase I study has been consistent with our expectations in this group of heavily pretreated patients; as has been the observed anti-tumor activity. These findings allow Arno to continue advancing the onapristone development program."
Onapristone is an oral, anti-progestin hormone blocker that has been shown in previous Phase II clinical trials (not sponsored by Arno) to exhibit anti-tumor activity in patients with breast cancer. In pre-clinical testing, onapristone has been shown to block the activation of the progesterone receptor (PR), which is believed to be a mechanism that inhibits the growth of activated progesterone receptor (APR) driven breast, endometrial and other, primarily gynecological tumors. APR has the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic currently under development.
Arno Therapeutics has improved the manufacturing process for onapristone and developed a proprietary, sustained release formulation to avoid the high peak concentrations associated with previously investigated immediate release type formulations and to allow the continuous suppression of the APR. The ongoing, open-label Phase I study is currently enrolling patients and is designed to evaluate the safety of onapristone in the selected patient population, determine the recommended Phase II dose, and assess any antitumor activity. This multi-site trial is taking place in France and is expected to enroll a total of approximately 70 patients. Arno is working with Biotrial S.A.S., a drug evaluation and pharmacology research company, as its contract research organization for this trial.
To date, the Phase I clinical trial has enrolled 48 patients with PR positive tumors in the dose escalation stage, including 28 patients with gynecologic malignancies and 19 patients with breast cancer. Prior to entering this study, these heavily pre-treated patients had, on average, previously received three chemotherapy treatment regimens and one hormone therapy regimen. In general, onapristone was well tolerated without substantial dose limiting toxicities. A total of three patients experienced Grade 3 liver function test abnormalities associated with progression of liver metastases and discontinued onapristone treatment. None of these adverse events were deemed to be drug-related by an independent safety review committee. Currently, 15 patients from the dose escalation stage are still receiving onapristone therapy in the study.
Five of the 48 patients enrolled in the dose escalation stage have been on study for less than eight weeks and are awaiting their first disease assessment evaluation. Of the 43 evaluable patients, one patient with serous ovarian cancer receiving 10mg twice daily of the extended release formulation has had a durable partial response (ongoing at 24 weeks). In addition, 5 of 26 patients with gynecologic tumors and 2 of 16 patients with breast tumors have stable disease for greater than 16 weeks.
Dr. Zukiwski added, "We are encouraged by these data, especially that which relates to the anti-tumor activity of onapristone observed in patients with gynecological malignancies, as we are targeting our proposed registration trial to evaluate onapristone in endometrioid cancer. To date, of the 24 evaluable patients with gynecological malignancies, one patient achieved a partial response with greater than 30% reduction in tumor size and five patients had stable disease for more than 16 weeks - which is a promising signal considering that less than 50% of patients with gynecological cancers have APR positive tumors. Overall, these results demonstrate that the recommended Phase II dose of 50mg onapristone has an acceptable safety profile and that anti-tumor activity was observed in the study."
The proposed registration study in endometrioid cancer will be conducted in conjunction with a diagnostic test targeting women with tumors expressing the APR. The current Phase I study does not prospectively test for APR, but research conducted by Arno indicates that approximately 45% of all endometrioid tumors are APR positive.
About Endometrial Cancer
In the United States, about 52,630 cases of cancer of the uterine corpus (body of the uterus) are expected to be diagnosed in 2014. These usually occur in the endometrium (lining of the uterus). About 8,590 deaths are expected in 2014.
About Arno Therapeutics
Arno Therapeutics is a clinical stage biopharmaceutical company developing innovative products for the treatment of cancer. Arno has exclusive worldwide rights to develop and market three innovative anti-cancer product candidates. These compounds are in clinical or preclinical development as product candidates to treat hematologic malignancies and solid tumors. For more information about the company, please visit www.arnothera.com.
Forward-Looking Statements: This press release contains forward-looking statements that involve substantial risks and uncertainties. These statements are often, but not always, made through the use of words or phrases such as "anticipates," "expects," "plans," "believes," "intends," and similar words or phrases. These forward-looking statements include, without limitation, statements regarding the number and tumor type of patients to be enrolled in the Phase I expansion stage, statements regarding the timing, progress and anticipated results of the clinical development of onapristone, statements regarding the potential of onapristone as a treatment for gynecological and other cancers, statements regarding Arno’s use and development of a diagnostic test to identify patients with APR tumors, statements regarding the potential of APR to function as a biomarker for anti-progestin activity, as well as Arno's strategy, including its strategy to target endometrioid cancer in a proposed registration trial, future operations, outlook, milestones, future financial position, future financial results, plans and objectives. We may not actually achieve these plans, intentions or expectations and Arno cautions investors not to place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Various important factors could cause actual results or events to differ materially from the forward-looking statements that we make. Such factors include, among others, risks that the results of clinical trials will not support our claims or beliefs concerning the effectiveness of onapristone or any of our other product candidates, our ability to successfully develop a diagnostic to identify APR tumors, our ability to finance the development of our product candidates, regulatory risks, and our reliance on third party researchers and other collaborators. Additional risks are described in the company's Annual Report on Form 10-K for the year ended December 31, 2013. Arno is providing this information as of the date of this press release and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.
The Ruth Group
Lee Roth (investors)
Kirsten Thomas (media)