Kaletra is to be used for the treatment of HIV infection in adults and children six months and older in combination with other antiretroviral medications. This medication has been proven in clinical trials to be effective in patients who are new to, as well as those experienced with, HIV therapy. At present there are no results from controlled trials evaluating the effect of Kaletra on the progression of HIV past 72-week studies.
In the first double-blind, ongoing pivotal clinical trial comparing two protease inhibitors in 653 patients new to antiretroviral therapy (study M98-863), Kaletra in combination with Zerit (stavudine/d4T) and Epivir (lamivudine/3TC) reduced the HIV RNA, or viral load to below detectable levels (less than 400 copies/ml) in 79% of the patients compared to 70% of patients on combination of Viracept (nelfinavir), d4T and 3TC. This difference between the Kaletra and Viracept treatment groups was statistically significant. These data were evaluated using an intent-to-treat (ITT) analysis, which captures data on all study participants, including those who left the study early for any reason and were considered treatment failures. Through 24 weeks, only two percent of patients discontinued from each treatment group due to study drug-related side effects. The side effects for Kaletra included diarrhea, nausea, asthenia, abdominal pain, vomiting and headaches. A slightly higher rate of Grade 3/4 cholesterol and triglycerides elevation was seen in the Kaletra group versus the nelfinavir group. The total discontinuation rate was fourteen percent for the Kaletra group and twelve percent for the nelfinavir treatment group.
An expanded access program is designed to make experimental drugs for life-threatening illnesses that are pending FDA approval available to patients at no charge to the patient. The program is paid for and operated by pharmaceutical companies with "guidance" from the US Food and Drug Administration (FDA). The program is scaled down and eventually closed when the experimental agent receives FDA marketing approval and becomes widely available by prescription.
To be eligible for the Videx EC expanded access program you must be HIV positive, 16 years old or older, have been unable to tolerate Videx tablets or oral solution in the past, be available for regular follow ups with your physician and be able to understand and willing to give informed consent. To enroll in this program your physician must call 1-877-418-3889. This may be the shortest ever expanded access program in history. The program opened October 1, 2000, and the FDA approved Bristol Myers Squibb's application for marketing approval on October 31. As of press time, Videx EC had been approved, although it had not reached the pharmacies yet.
A Phase I study demonstrated that once daily dosing is safe and well tolerated. Ian Sanne, MD, of Johannesburg Hospital in Johannesburg, South Africa presented 24-week results from a Phase II study. The Phase II multi-national, randomized study compared the safety and anti-HIV activity of three doses of BMS 232632 (200 mg., 400 mg., 500 mg.) with 750 mg. Viracept dosed three times daily. Twenty-one patients received Viracept in combination with Zerit (stavudine/d4T) and Videx (didanosine/ddI), while BMS 232632 was administered both as monotheraphy (for two weeks) and then in combination with Zerit and Videx to 78 treatment naive (no prior anti-HIV therapy) patients with HIV viral loads >2,000 copies per milliliter (c/ml). The mean (average) baseline HIV RNA was 4.8 log 10 copies per milliliter and a mean baseline CD4 (T Cell) count of 386 per micrometer.
The side effects included diarrhea (24% among BMS 232632-treated patients versus 75% among Viracept-treated patients), nausea (24% BMS vs. 15% Viracept). The most common laboratory abnormality was hyperbilirubinemia (elevated bilirubin levels) among 62% of patients treated with BMS 232632, although this abnormality was not associated with elevated liver enzymes, according to the investigator. Additionally, patients on BMS 232623 showed no signs of changes in lipid (blood fat) levels, while within four weeks. Those in the Viracept arm showed signs of increased in cholesterol, LDL cholesterol and trigliceride levels.
Phase III studies are expected to begin soon. They will look at and evaluate the effectiveness of BMS 232632 and safety. The studies will begin in the US, Europe and South America. Additionally, at a community treatment advocates update at the 40th ICAAC meeting, BMS made the announcement that the company is ready to begin planning an "expanded access" program for BMS 232632.