MIAMI BEACH Dosing, speed of onset, and extent of spread are among differences to anticipate with a second botulinum toxin expected to reach the U.S. market soon, according to physicians who evaluated its safety and efficacy in preclinical trials.

The Food and Drug Administration is reviewing data for Reloxin (botulinum toxin, Ipsen). "This is really excitingthe first new toxin in the market since Botox," Dr. Mark Nestor said at the South Beach Symposium. "We are hoping it will be approved in the next few months."

"The starting out point for us, especially if it comes in a 300-unit vial, is to do the same thing you do now with Botox," said Dr. Nestor, a dermatologist in private practice in Aventura, Fla., and clinical associate professor of dermatology and cutaneous surgery at the University of Miami. "Start out conservatively, and you will finesse this over time." Dr. Nestor is a speaker and consultant for and has received research grants from Medicis. He is also an advisory board member and speaker for Allergan.

There are four important studies that demonstrate its safety and efficacy, said Dr. Joel L. Cohen, principal investigator of one and assistant clinical professor of dermatology at the University of Colorado, Denver. Two studies assessed patient response to a single 50-U treatment and two others to repeat injections over time. Dr. Cohen is a consultant for Medicis and Allergan.

Median time to onset of effect was 2 days in a study of 300 patients who received Reloxin or placebo to treat the glabellar area. At 3 days, about half of patients felt an effect, and by 7 days, cumulative response was 90%, according to patient diaries. Investigators reported median response duration of 117 days. Nine patients had eye problems, including ptosis. A total of five patients experienced serious adverse events, but none were considered related to treatment, said Dr. Cohen, who is also in private practice in Englewood, Colo. Incidence of headache and injection site bleeding were similar to placebo.

A 90% response was also reported in another single treatment trial with 158 patients receiving either the toxin or placebo. There were some slight differences in efficacy compared to the other single treatment trial. Patient diaries indicated median time to effect of 3 days. Researchers found an 85-day median duration of effect. Reloxin also was well tolerated in this study, Dr. Cohen said.

Up to five repeat treatment sessions were allowed in an open-label, multicenter study. Researchers found a greater proportion of responders at each follow-up evaluation. They reported an overall 93% response and 73% of participants had at least a two-grade improvement. Patients older than 65 years were less likely to respond to Reloxin, as were those with severe ratings at baseline. In addition, the toxin appeared to work better in women, compared with men. Repeat injections were well tolerated, Dr. Cohen said.

The majority of treatment-emergent adverse events were mild. Injection site events, ocular events, and headaches were the most common. There were 72 severe adverse events during the study, including 1 death by gunshot, all unrelated to treatment.

Dr. Cohen and his colleagues also conducted a repeat injection study that found no difference between toxin and placebo patients in terms of vital signs or serum assays (no patient developed antibodies). This study included 768 patients allowed up to eight repeat treatments over 2 years. The multiple cycles were well-tolerated and effective, he said. Injection site pain and nasopharyngitis were the most common adverse events. A total of 37 participants had at least one treatment-emergent adverse event, 2% of which were severe.

The injection technique and pattern will be similar because the mechanism of action is the same for Reloxin and Botox (Allergan), Dr. Michael A.C. Kane said. He has served as an adviser and consultant to Medicis and Allergan.

"The dose-response curves are not parallel, so there is no simple conversion between Reloxin and Botox. "It cannot be a simple number multiplier, period," according to Dr. Kane, attending plastic surgeon at the Manhattan Eye, Ear and Throat Hospital in New York City.

Patients who have had both Botox and Reloxin say Botox is a gradual change over days, Dr. Kane said. "The biggest difference [with Reloxin is] patients say it's almost like a sledgehammer hits thema much more abrupt feelingthey really feel it kick in."

"Migration is probably the biggest issue we will hear," Dr. Kane said. Tissue migration may be related to complex size, and Botox is a larger 900 kd, compared with 500-600 kd for Reloxin. "We know bigger things move more slowly in muscle. But they would have you believe the smaller molecules of Reloxin will spread all over the place."

To put the differences in perspective, Dr. Kane said, "The hyaluronic acid fillers will vary by a greater degree than the differences between the different toxins."

Botox and Reloxin Are Similar but Different