Vernalis Announces Striking Weight Loss in Phase I Study with V24343 in Overweight and Mildly Obese Volunteers
LONDON, Sept. 13, 2007-VernalisÂ today announced the results of its Phase I programmeÂ with the CB1 antagonist, V24343 which has completed two Phase I studies: a single and multiple ascending dose study for up to 14 days, and a food effect study.
- Striking weight loss over 16 days in overweight and mildly obese volunteers
- Evaluated in a total of 66 volunteersÂ
- Generally well tolerated with no serious adverse events
- Evidence of efficacy also demonstrated by clinically relevant reductions in body fat, energy intake and waist circumference
- Pre-clinical data demonstrated significant safety differences from Sanofi-aventis CB1 antagonist, rimonabant.
Simon Sturge, CEO of Vernalis commented "We are very excited by theseÂ preliminary results which, if confirmed over longer studies, will be of significant benefit to overweight and obese patients.Â We stated from the outset of this trial that it is our intention to seek a partner for this programme, a process which is enhanced by such promising data".
Safety and Tolerability
V24343 was generally well tolerated over the dose range with two patients withdrawing due to adverse events (nausea and vomiting) in the highest dose cohorts. Other tolerability events were as expected for a CB1 antagonist. There were no serious adverse events.
Measures of efficacy were taken in the multiple ascending dose study in which patients were treated at 4 daily dose levels of 5mg, 15mg, 50mg and 100mg. In this trial, there were clear beneficial effects of V24343 at all dose levels across multiple parameters including weight loss, waist circumference, body fat and energy intake.
Average weight loss after 16 days was 0.5kg for placebo, 2.6kg for 5mg V24343 and 5.0kg for 100mg V24343. This compares very favourably with results for rimonabant in a similar trial in obese volunteers over 1 week, which showed placebo-corrected weight loss of 0.7kg.
Differentiation from Rimonabant
The striking weight loss demonstrated in the Phase I study above gives further credence to the effectiveness of CB1 antagonists as weight loss agents. The U.S. Food and Drug Administration (FDA) advisory committee decision to not support the approval of rimonabant for a number of reasons, including risks associated with depression, may be relevant to this class of drug. However, the question as to whether or not other CB1 antagonists can achieve similar or improved efficacy without major side effects remains open. Indeed, V24343 has shown a number of
distinguishing features over rimonabant in pre-clinical studies including:
Â Â -A markedly reduced propensity for neurological adverse events
Â Â -Lower propensity to induce nausea and GI disturbance
Â Â -Improved metabolic profile.
More lengthy trials will be required to evaluate fully the long-term safety andÂ efficacy of this product in the treatment of obesity and other indications such as management of diabetes.