More than 64 years after baseball Hall-of-Famer Lou Gherig died of amyotrophic lateral sclerosis - a disease that has since taken on his name - CytRx Corp. has moved its small-molecule drug arimoclomol into a Phase II trial.

"Patients who have Lou Gherig's disease can now go to one of eight to 10 sites around the [U.S.]," said Steven Kriegsman, president and CEO of the Los Angeles-based company. "It's an opportunity to help them because right now there's really nothing available that really does any good. It's a disease that has no effective treatment."

The double-blind, placebo-controlled Phase II trial will enroll 80 ALS patients who will receive one of three dose levels of arimoclomol capsules three times a day for 12 weeks, or a placebo. Researchers are testing the drug for its safety and tolerability. Secondary endpoints include a preliminary evaluation of efficacy using an assessment of lung capacity, as well as the revised ALS Functional Rating Scale, which is used to determine a patient's capacity and independence in 13 functional activities.

The trial is expected to be completed in the first half of 2006, and would be followed by a Phase IIb study designed to detect more subtle efficacy responses in about 300 ALS patients at 25 clinical sties. That second trial is expected to take about 18 months.

Lou Gherig's disease, or ALS, is a progressive degeneration of the brain and spinal column nerve cells that control the muscles. It causes increasing muscle weakness, inability to control movement and difficulty speaking, swallowing and breathing.

About half of ALS patients die within 18 months of diagnosis and 80 percent die within five years. The care of one patient costs about $200,000 a year.

In Europe, ALS is called Charcot's disease, named after the doctor who discovered it in 1874 in Paris. It gained notoriety in the U.S. when New York Yankees first baseman Lou Gherig died of it in 1941 at the age of 37.

In the U.S., an estimated 30,000 people have the disease and almost 6,000 new cases are diagnosed annually, according to the ALS Association.

Patients currently are treated with Paris-based Sanofi-Aventis Group's Rilutek, the only FDA-approved treatment for the disease, which improves patient survival by a few months.

"Our drug, arimoclomol, could be a miracle drug for those people with Lou Gherig's disease who die and suffer a horrendous, debilitating slide to death," Kriegsman told BioWorld Today. "Your mind is working perfectly and you can smell and you can taste and you can hear, but everything else shuts down. Eventually, you die of respiratory failure."

Arimoclomol is believed to work by stimulating a normal cellular protein repair pathway by activating "molecular chaperones." Since damaged proteins are thought to play a role in many diseases, CytRx believes that activation of molecular chaperones could have therapeutic efficacy for other afflictions, including Parkinson's, Huntington's, cystic fibrosis and Type II diabetes.

Elemer Piros, an analyst with New York-based Rodman & Renshaw, said arimoclomol's market potential exceeds $1 billion, if it shows a "significant impact on survival" in ALS. He removed his "under review" rating of CytRx shares Thursday and upgraded the company to "market outperform/speculative risk" with a 12-month price target of $3.50 per share.

CytRx's stock (NASDAQ:CYTR) rose 2 cents Thursday to close at 87 cents.

In Phase I trials, arimoclomol was well absorbed and well tolerated in healthy volunteers. The FDA granted it orphan drug designation in May for the treatment of ALS. Kriegsman said he didn't know of any other company that has an ALS therapy in Phase II development.

"A lot of trials have been attempted," Kriegsman said. "Amgen did a trial; Cephalon did a trial; Novartis did a trial. But in essence, I think they had the wrong compound. They didn't have the necessary technology at that time."

Arimoclomol is one of the few compounds, out of more than 70 tested in preclinical trials, that has demonstrated a benefit following disease onset, he said.

"In mouse models, the average life span was over 22 percent longer" in those treated with arimoclomol, Kriegsman said, who added that a sister compound, bimoclomol, has been used in more than 300 people for as long as 48 weeks with no serious drug-related adverse events.

CytRx filed its investigational new drug application for the Phase II trial in May, but the FDA placed the study on clinical hold two months later pending review of additional information, namely existing clinical safety data of the related compound bimoclomol. It also had to file an amendment of the protocol to include specific clinical tests to be administered to enrolled patients.

CytRx acquired both compounds, as well as iroxanadine for diabetes and cardiovascular disease, for about $3 million plus milestone payments in October 2004 from Biorex Research & Development RT, of Veszprem, Hungary, which spent more than $63 million to develop the drugs. (See BioWorld Today, Oct. 6, 2004.)

"I think we have about 94 patents worldwide," Kriegsman said. "We have about 16 years of patent protection. If we get this drug to market, it's potentially a $2 billion drug worldwide."

Arimoclomol is not partnered, but Kriegsman said several pharmaceutical and large biotechnology companies have shown an interest.

"If an opportunity arises that is good for the shareholders and good for CytRx, we'll obviously consider it," he said.

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