"We remain enthusiastic about the prospects for arimoclomol as a potential drug candidate for neurodegenerative disease, and are seeking a corporate partner with which to develop it," said Steven A. Kriegsman, Chief Executive Officer of CytRx. "We are delighted that the ALS Association and the FDA's OOPD are willing to provide all of the financial support for this Phase 2/3 clinical trial of arimoclomol in this rapidly-progressing form of ALS."
The double-blind, placebo-controlled, adaptive clinical trial design allows for the seamless transition from a Phase 2 safety and tolerability study to a planned overlapping Phase 3 efficacy study. fALS subjects with SOD1 gene mutations will be randomized 1:1 to receive either 100 mg oral arimoclomol or a placebo three times daily. This arimoclomol dose is the same as the highest dose level administered in CytRx's prior Phase 2a and open label clinical trials for sporadic ALS. In addition to standard clinical safety monitoring several indicators of disease progression will also be measured including the ALS Functional Rating Scale Revised (ALSFRS-R).
Co-principal investigators for the study are Michael Benatar MBChB, MS, DPhil, Associate Professor of Neurology and Epidemiology at Emory University, and Merit Cudkowicz, MD, Associate Professor at Harvard Medical School. According to Dr. Benatar, "We are very pleased to be able to test arimoclomol in patients with mutations in the SOD1 gene. With this mutation the diagnosis of ALS can be made with confidence based on less prominent clinical features allowing initiation of treatment to begin at an earlier stage in the disease process."
The Phase 2 trial is expected to require approximately 18 months to enroll 30 subjects who will be treated continuously for 12 months. Once the last subject has been treated for 6 months an interim analysis will be performed to determine safety, tolerability, and feasibility. This analysis will determine whether or not to proceed to the Phase 3 trial and if so, how many additional subjects would need to be enrolled to power the study sufficiently to detect at least a 30% decrease in the rate of disease progression over a 12 month period using the ALSFRS-R. Data from these Phase 2 subjects will be included in the data analysis of the planned Phase 3 trial. If results from the Phase 2 interim analysis merit continuation to Phase 3, it is estimated that an additional 50 subjects will be enrolled. It is expected to require approximately 18 months to enroll these 50 subjects, who will be treated with either arimoclomol or placebo for 12 months as in the Phase 2 trial. Additional information regarding the clinical trial is available at http://www.clinicaltrials.gov.
The Company estimates that there are approximately 600 patients with fALS who have mutations of the SOD1 gene in the U.S. To accelerate recruitment for this two-center clinical trial, study participants will be required to travel to either Emory University or Massachusetts General Hospital for two clinical evaluations (baseline and Month 2), while the remaining clinical monitoring during Months 1, 3, 5, 6, 8, and 10 will be performed partly via telephone and partly via visits from a medical specimen collection service in the subjects' own home. The last visit (Month 12) will be conducted by a travelling clinical coordinator from either Emory or Massachusetts General Hospital.
Arimoclomol is a molecular chaperone regulator drug candidate that is being considered as a treatment for ALS and stroke recovery. Molecular chaperone regulator drugs are believed to function by regulating a normal cellular protein repair pathway through the activation or inhibition of "molecular chaperones." Molecular chaperones detect proteins that are misfolded, and have the ability to refold those proteins into the appropriate, non-toxic shape. Arimoclomol has been studied in seven Phase 1 and two Phase 2 clinical trials without any significant adverse events. CytRx's Phase 2b clinical trial with arimoclomol as a treatment for ALS was placed on clinical hold by the FDA in January 2008, unrelated to any data generated by human studies, and additional preclinical toxicology studies are underway to resolve this issue. The Company expects to file data from those additional toxicology studies with the FDA in the second quarter of 2009. If the arimoclomol clinical hold is removed, CytRx intends to seek a partner for the development of arimoclomol for all indications on a worldwide basis.
ALS is a progressive degeneration of the brain and spinal column nerve cells that control the muscles that allow movement. ALS is a common neuromuscular disease, affecting an estimated 120,000 people of all races and ethnic backgrounds worldwide. Over a period of months or years, ALS causes increasing muscle weakness, inability to control movement and problems with speaking, swallowing and breathing. According to the ALS Association more than 5,600 people in the U.S. are diagnosed with ALS annually and an estimated 30,000 Americans have ALS at any given time. According to the National Institute of Neurological Disorders and Stroke, most ALS patients die within three to five years after the onset of symptoms.
About the ALS Association
The mission of the ALS Association is to lead the fight to cure and treat ALS through global, cutting-edge research, and to empower people with Lou Gehrig's disease and their families to live fuller lives by providing them with compassionate care and support.
About CytRx Corporation
CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The CytRx drug development pipeline includes programs in clinical development for cancer indications, including tamibarotene in a registration study for the treatment of acute promyelocytic leukemia (APL). CytRx is developing two drug candidates based on its industry-leading molecular chaperone technology, which aims to repair or degrade misfolded proteins associated with disease. The Company owns and operates a research and development facility in San Diego. CytRx also maintains a 45% equity interest in publicly traded RXi Pharmaceuticals, Inc. (NASDAQ: RXII). For more information on the Company, visit http://www.cytrx.com.
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks relating to the timing, outcome or results of the independent clinical testing of arimoclomol in patients with the inherited or familial form of ALS, the risk that the results of the Phase 2 stage of the clinical trial will not justify proceeding with the Phase 3 stage of the trial, the risk that the sponsors of the Phase 2/3 trial will choose not to proceed with the study due to the results of the study, financial matters, or other reasons, the risk that there will not be a sufficient number of potential patients to power the Phase 3 stage of the trial to achieve the trial's currently contemplated endpoints, or that the cost of enrolling a sufficient number of patients will be prohibitive, uncertainties related to the impact of the FDA's clinical hold on the Company's planned Phase IIb arimoclomol clinical trial for ALS on the timing and ability to resume that clinical testing at the desired higher dosage of arimoclomol, the risk that any requirements imposed on the Company's planned clinical trial designs for ALS by the FDA as a result of the concerns expressed in their clinical hold of the Company's ALS program might adversely affect the Company's ability to demonstrate that arimoclomol is efficacious in treating ALS, risks related to CytRx's need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, risks related to the future market value of CytRx's investment in RXi and the liquidity of that investment, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx's most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.