Investors of CytRx Corp. can breathe a sigh of relief after the FDA lifted a nearly two-year hold on molecular chaperone amplifier arimoclomol in amyotrophic lateral sclerosis, an event that positions the firm to resume Phase IIb testing and kicks partnering talks back into high gear.
As Steven A. Kriegsman, president and CEO of the Los Angeles-based firm, told BioWorld Today, "We're back in business.
"We told the Street we'd have the hold lifted in the fourth quarter, and we met that milestone," he added.
The FDA placed the clinical hold in January 2008, just a few weeks after the Phase IIb trial had been initiated, to request additional preclinical studies. The company said the hold was based on animal toxicology data and did not stem from any human data generated up to that point. (See BioWorld Today, Jan. 23, 2008.)
The company completed additional preclinical work earlier this year and submitted it to the FDA, which now has allowed the trial to continue up to the planned target dosage level of 400 mg three times daily, Kriegsman said.
In the meantime, CytRx moved arimoclomol into a Phase II/III trial in a small subset of ALS patients with the familial form of the disease with mutations in the superoxide dismutase-1 gene. That study, funded by grants from the ALS Association and the FDA's Office of Orphan Products Development, was not affected by the clinical hold. (See BioWorld Today, Feb. 24, 2009.)
"That study's doing nicely, and we continue to make progress along those lines," Kriegsman said, but the Phase IIb trial in a broader ALS population is "our major study," and is what CytRx - and prospective partners - clearly has its sights on.
Getting the clinical hold lifted "opens up the possibility of strategic alliances that also have been on hold," he said. Going forward, the company will operate a "two-pronged approach," moving into discussions with potential partners while "we get things going in a clinical setting."
The Phase IIb trial is set to test progressive groups - each comprising about 20 to 30 ALS patients - over a three-month treatment period. Fifteen patients will receive a combination of arimoclomol at various dose levels and riluzole at a fixed dose of 50 mg daily, with between five and 15 patients receiving placebo and riluzole.
Riluzole, marketed by Paris-based Sanofi-Aventis SA as Rilutek, is the only ALS therapy available for patients, but its efficacy is limited.
The trial's endpoints include a preliminary evaluation of efficacy, as measured by the revised ALS Functional Rating Scale and vital capacity, the assessment of lung capacity.
Arimoclomol, which has fast-track and orphan status in the U.S. and orphan status in Europe, also has shown early promise in other neurodegenerative conditions such as stroke recovery, "so this drug could be a huge winner for us," Kriegsman said.
Elsewhere in its pipeline, CytRx has tamibarotene, which is in Phase II testing in acute promyelocytic leukemia, earlier-stage molecular chaperone programs and iroxanadine, a small molecule aimed at treating diabetic complications that it plans to partner.
The company ended the third quarter with about $35 million in cash, with a burn rate of about $750,000 to $800,000 per month, Kriegsman said. "So we have cash for the next two and a half years."
CytRx also owns about 36 percent of RXi Pharmaceuticals Inc., a Worcester, Mass.-based pure-play RNAi company spun out of CytRx in early 2007, which it could sell for nondilutive funding.
In addition, the firm has an $80 million shelf on file, though "we don't feel our stock price justifies a drawdown right now," Kriegsman said.
Shares of CytRx (NASDAQ:CYTR) closed Wednesday at $1.08, up 8 cents, or 8 percent.