In a late-stage clinical trial, Merck's investigational quadrivalent human papillomavirus (HPV) vaccine, Gardasil, showed the vaccine is capable of preventing 100% of high-grade cervical precancers known as cervical intraepithelial neoplasia (CIN) as well as noninvasive cervical cancers, such as adenocarcinoma in situ (AIS), associated with HPV types 16 and 18. More than 12,000 women between the ages of 16 and 26 participated in the prospective, randomized, double-blind, placebo-controlled study, know as Future II.
In a late-stage clinical trial, Merck's investigational quadrivalent human papillomavirus (HPV) vaccine, Gardasil, showed the vaccine is capable of preventing 100% of high-grade cervical precancers known as cervical intraepithelial neoplasia (CIN) as well as noninvasive cervical cancers, such as adenocarcinoma in situ (AIS), associated with HPV types 16 and 18. More than 12,000 women between the ages of 16 and 26 participated in the prospective, randomized, double-blind, placebo-controlled study, know as Future II. Women were first screened to make sure they did not have HPV, then randomized to receive either vaccine or placebo injections. The women were monitored for approximately two years
The primary analysis revealed that no cases of CIN or AIS were reported among 5,301 patients receiving Gardasil compared with 21 cases reported among 5,258 patients who received placebo. A secondary analysis included the original HPV-free study group as well as women who may have become infected during the vaccination period, and women who committed significant violations of study protocol, such as missing a visit. In this group, only one case of CIN or AIS was reported in the 5,736 women who received the vaccine compared with 36 cases in the 5,766 women who received placebo.
Gardasil targets HPV Types 16 and 18, which account for 70% of cervical cancers, and HPV Types 6 and 11, which account for 90% of genital warts. Merck plans to submit a Biologics License Application for Gardasil to the FDA in the fourth quarter of 2005.
Diabetic nephropathy is the leading cause of chronic renal failure in the United States. It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes. About 20% to 40% of patients with Type 1 or Type 2 diabetes develop nephropathy. Speedel Pharmaceuticals hopes its investigational endothelin A receptor antagonist (ERA), SPP301, will help address this large and growing unmet medical need. SPP301 is a second-generation ERA that was specifically optimized for improved liver safety.
The biopharmaceutical company successfully completed phase II trials of SPP301 in March 2005, in which clinically relevant efficacy was observed with SPP301 after four weeks of treatment. SPP301 was tested in patients who were on high doses of angiotensin receptor blockers, and decreased 24-hour proteinuria in a clinically relevant manner. In July the company announced the start of its phase III study. The ASCEND study is a randomized, placebo-controlled morbidity and mortality study with over 2,000 patients. It is designed to assess time to doubling of serum creatinine, end-stage renal disease, or death in Type 2 diabetes patients with overt diabetic nephropathy. Patients will be given either 25 mg or 50 mg of SPP301 once daily on top of standard therapy, or they will receive standard therapy alone. The company estimates that it should take about 3.5 years for enough events to occur in the composite end-point to demonstrate statistically significant efficacy.
SPP301 has been granted fast-track designation and has undergone a special protocol assessment by the FDA.
First in a new class of antiepileptics
Also set to begin phase III studies is Valeant Pharmaceuticals' retigabine, in development as an adjunctive treatment for partial-onset seizures in patients with epilepsy. Retigabine works as a potassium-channel opener and a potentiator of gamma aminobutyric acid. According to the company, this new mechanism of action represents a major advancement in the treatment of partial-onset seizures and may be a key differentiating factor in the treatment of epilepsy when combination therapy is warranted.
In November the results from the completed phase II trial for retigabine will be presented at the 18th World Congress of Neurology. The study, which consisted of four treatment groups, showed median monthly seizure rates decreasing by 13% in the placebo group and 23%, 29%, and 35% in the retigabine groups. Results were statistically significant in the two higher doses (900 mg/day and 1200 mg/day) compared with placebo. The most common adverse events were related to the central nervous system and included somnolence, dizziness, confusion, speech disorder, vertigo, tremor, amnesia, thinking abnormality, abnormal gait, incoordination, ataxia, and paresthesia.
Results from the two phase III studies are anticipated to be available in the second half of 2007.