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CytRx's Arimoclomol Meets Primary Safety and Tolerability Endpoints in Phase IIa ALS Clinical Trial

Posted on: Tuesday, 26 September 2006, 09:00 CDT

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.

Source: Business Wire

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