LOS ANGELES--(BUSINESS WIRE)--CytRx Corporation (Nasdaq:CYTR) today announced that its lead drug candidate arimoclomol was shown to be safe and well tolerated at all three doses tested in its Phase IIa clinical trial in patients with amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease).
In the 10-center, double-blind, placebo-controlled Phase IIa trial, ALS patients received placebo or arimoclomol in one of three dose levels (25 mg, 50 mg or 100 mg) three times daily for 12 weeks and then were studied for an additional four weeks without treatment. Eighty-four patients with ALS entered the clinical trial with only seven withdrawing prior to completion of dosing. No statistically significant treatment-related increases in adverse events were reported, and encouragingly, arimoclomol-treated patients reported fewer asthenia (weakness) adverse events than the patients receiving placebo. The minor treatment-related changes in laboratory results that reached statistical significance were well within the normal safety range and did not change with time or dose, and therefore were considered to be clinically unimportant. No treatment-related effects on vital signs, electrocardiogram or body weight were observed. Based on these results, CytRx plans to proceed with activities associated with initiating a Phase IIb clinical trial with arimoclomol for the treatment of ALS in the first half of 2007, subject to FDA approval.
One of the secondary endpoints of the trial included an analysis of pharmacokinetics (drug oral absorption, distribution, and removal). While full analysis of these data is not yet complete, tests indicate that arimoclomol effectively entered the cerebral spinal fluid, demonstrating that the drug passed the “blood:brain barrier,” overcoming a potential impediment for the development of drugs like arimoclomol that are intended to treat neurodegenerative diseases. The average amount of drug detected in the cerebral spinal fluid was similar to the amounts present in blood and increased with increasing doses.
Additional secondary endpoints of the trial included a preliminary evaluation of the disease progression markers, the Revised ALS Functional Rating Scale (ALSFRS-R) and vital capacity (VC). The ALSFRS-R is used to determine a patient’s capacity and independence in 13 functional activities and VC is an assessment of a patient’s breathing capacity. As previously announced the Phase IIa clinical trial was designed with a scale and scope to show statistical significance with respect to safety and tolerability, with the planned monitoring of the rate of disease progression using ALSFRS-R and VC designed to show statistical significance only in the case of extreme responses to drug treatment. While disease progression was measured as a secondary endpoint, the primary purpose of the trial was to generate sufficient data regarding safety and tolerability to determine whether to proceed with a significantly larger Phase IIb clinical trial designed primarily to detect efficacy. As was expected by CytRx due to the limited size and duration of the trial, arimoclomol did not show a statistically significant change in disease progression as measured by these markers. However, the average decrease in ALSFRS-R score for those patients receiving the highest dose of arimoclomol was higher than the placebo group at all time points except week 12 after dose initiation (i.e. it was higher at weeks 4, 8 and 16 and substantially the same at week 12). This trend of higher ALSFRS-R scores in the high dose group relative to the placebo was not observed with VC as the indicator of disease progression.
CytRx’s Senior Vice President of Drug Development Dr. Jack Barber said, “The results of the Phase IIa trial are encouraging for the future development of arimoclomol in that even the highest dose was shown to be safe and well tolerated in a patient population that has virtually no treatment options. Encouragingly, arimoclomol effectively reached the cerebral spinal fluid, which is the site of the ALS-degenerating motor neurons. This ability to cross the blood:brain barrier can otherwise be a significant hurdle for potential treatments of neurodegenerative diseases including ALS. These results confirm that arimoclomol is worthy of progression to the planned Phase IIb efficacy trial.”
CytRx President and CEO Steven A. Kriegsman said, “CytRx is committed to help those suffering from this deadly neurodegenerative disease. We are delighted our trial met the primary Phase IIa endpoints and we now plan to work with the FDA to develop the protocol for a Phase IIb efficacy study. While we are still in the planning stages of this subsequent trial, subject to FDA approval we expect that approximately 390 ALS patients enrolled at 30-35 clinical sites in the United States and Canada will be treated at the highest arimoclomol dose level. The upcoming Phase IIb study is designed to enroll more patients and to be longer in duration in order to monitor changes in disease progression in a statistically significant fashion. We expect the Phase IIb trial to be completed about 18 months after patient enrollment begins. We believe that positive efficacy and safety results from the Phase IIb clinical trial could be sufficient for arimoclomol product registration for this indication.”
About Arimoclomol
Arimoclomol is one of CytRx’s three orally-administered, small molecule compounds. This small molecule drug candidate is believed to function by stimulating a normal cellular protein repair pathway through the activation of “molecular chaperones.” Since damaged proteins called aggregates are thought to play a role in many diseases, CytRx believes that activation of molecular chaperones could have therapeutic efficacy for a broad range of diseases.
The FDA has granted Fast Track designation and Orphan Drug status to arimoclomol for the treatment of ALS. Fast Track is designed to facilitate the development and expedite the regulatory review of a new drug that demonstrates the potential to address a significant unmet medical need for the treatment of a serious or a life-threatening condition. Orphan Drug status holds numerous potential benefits, including opportunities for grant funding towards clinical trial costs, tax advantages, FDA user-fee benefits, seven years of U.S. market exclusivity should the FDA grant marketing approval for the drug and an added mechanism for more frequent communication with the FDA.
About ALS
ALS is a progressive degeneration of the brain and spinal column nerve cells that control the muscles that allow movement. 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 Survival Guide, 50% of ALS patients die within 18 months of diagnosis and 80% die within five years. More than 120,000 people are living with ALS worldwide.
About CytRx Corporation
CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The Company owns three clinical-stage compounds based on its small molecule “molecular chaperone” co-induction technology. In September 2006 CytRx announced receipt of $24.5 million in a non-dilutive agreement with the privately funded ALS Charitable Remainder Trust to fund continued arimoclomol development for the treatment for ALS in return for one percent royalty payment from potential worldwide sales of arimoclomol for the treatment of ALS to The Greater Los Angeles Chapter of The ALS Association.
CytRx has previously announced that a novel polyvalent HIV DNA + protein vaccine exclusively licensed to CytRx, developed by researchers at the University of Massachusetts Medical School (UMMS) and Advanced BioScience Laboratories, and funded by the National Institutes of Health, demonstrated very promising interim Phase I clinical trial results that indicate its ability to produce potent antibody responses with neutralizing activity against multiple HIV viral strains. CytRx also has a broad-based strategic alliance with UMMS to develop novel compounds in the areas of ALS, obesity, type 2 diabetes and cytomegalovirus (CMV) using RNAi technology. The Company has a research program with Massachusetts General Hospital, Harvard University’s teaching hospital, to use RNAi technology to develop a drug for the treatment of ALS. CytRx Drug Discovery division, located in Worcester, Mass., focuses on the use of RNAi technologies to develop small molecule and RNAi therapeutics to treat obesity and type 2 diabetes. For more information, visit CytRx’s Web site at www.cytrx.com.
Forward-Looking Statements
This press release contains forward-looking statements, including those related to the preliminary results and achievements of CytRx’s clinical Phase IIa trial for arimoclomol, which involve known and unknown risks and uncertainties that may cause actual future results and achievements of CytRx to be materially different from those expressed or implied by these forward-looking statements. In particular, the preliminary results and achievements described may not be supported by further analysis of the Phase IIa trial data or by the results of any subsequent clinical trials. These risks and uncertainties also include risks and uncertainties regarding CytRx’s ability to obtain regulatory approvals for further clinical testing of arimoclomol, the scope of clinical testing that may be required by regulatory authorities and the timing and outcome of further clinical trials. Additional uncertainties and risks regarding regulatory approval of CytRx’s drug candidates, financing needs, reliance upon strategic relationships, intellectual property protections and other relevant matters are described in CytRx’s reports filed with the Securities and Exchange Commission, including 10-K, 10-Q and 8-K reports. All forward-looking statements in this press release are based upon information available to CytRx as of the date of this press release. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Contacts CEOcast, Inc. Kevin Theiss/Cormac Glynn, 212-732-4300 ktheiss@ceocast.com cglynn@ceocast.com
