PRNewswire - October 24, 2000

Kaletra, formerly known as ABT-378/r, is indicated for the treatment of HIV infection in adults and children as young as six months in combination with other antiretroviral medications. Accelerated approval of Kaletra is based on the response of viral load (amount of virus in the blood) measurements and CD4 cell count, both surrogate markers, from a 24-week controlled Phase III clinical trial and additional smaller open-label studies of 72 weeks in duration. The 72-week studies were designed to evaluate different doses of Kaletra and had no comparator groups. At present, there are no results from controlled trials evaluating the effect of Kaletra on the progression of HIV.

"Although Kaletra resistance may be observed with longer study, the lack of genotypic resistance detected to date with Kaletra in clinical trials in patients new to therapy is promising," said Eugene Sun, M.D., head of antiviral development, at Abbott Laboratories.

In an ongoing, international, multi-center, double-blind, randomized clinical trial of 653 patients new to HIV therapy, the Kaletra regimen was compared to a regimen containing Viracept(R) (nelfinavir), a widely-used protease inhibitor. In addition to the protease inhibitor, patients in each of the treatment groups also received two nucleoside reverse transcriptase inhibitors (3TC and d4T). In this study, 326 patients received the Kaletra regimen and 327 patients received the nelfinavir regimen.

Drug Resistance Analyses at 24 or 48 Weeks

Plasma viral isolates from all patients on treatment who had detectable HIV (>400 copies/mL) at either week 24 or 48 were analyzed for evidence of genotypic resistance. Of those, genotypic analysis results were available for 31 Kaletra patients and 64 nelfinavir patients. Viral resistance is one of the causes of viral rebound and subsequent treatment failure for people with HIV.

Results from this analysis showed that none (0/31) of the patients on the Kaletra regimen and 31 percent (20/64) of patients on the nelfinavir regimen exhibited genotypic resistance.

Viral Suppression at 48 Weeks

At 48 weeks, 75 percent (245/326) of patients randomized to the Kaletra regimen had undetectable levels of virus (<400 copies/mL) compared to 63 percent (206/327) of patients randomized to the nelfinavir regimen (p-value <0.001), based on an intent-to-treat (ITT) analysis. An ITT analysis captures data on all study participants. Participants with missing data at 48 weeks were considered treatment failures.

A separate analysis from the same study was presented on patients who remained on treatment (OT). On treatment analyses capture data for patients who remain on treatment and results at a particular time point, therefore, results from OT analyses are typically higher than results from ITT analyses. At 48 weeks, 93 percent (243/261) of patients taking the Kaletra regimen compared to 82 percent (205/251) on the nelfinavir regimen had undetectable HIV levels (<400 copies/mL) (p-value <0.001). In this study, Kaletra continues to be well-tolerated through 48 weeks, with only two percent of patients discontinuing due to Kaletra-related adverse events. Four percent of patients taking the nelfinavir regimen discontinued due to nelfinavir-related adverse events. The total discontinuation rate was 18 percent for patients taking the Kaletra regimen, and 23 percent for patients taking the nelfinavir regimen.

"These results are encouraging in two respects," said Dale Kempf, Ph.D., senior project leader, antiviral research, Abbott Laboratories. "First, no patients who experienced viral rebound at some point in the study exhibited resistance to Kaletra. Second, significantly more patients receiving Kaletra had viral suppression below detectable levels than the nelfinavir-treated patients."

"The literature suggests that understanding the level of genotypic resistance to HIV drugs is increasingly important," said Renslow Sherer, M.D., associate professor of medicine, Cook County Hospital and an investigator in the study. "Physicians should be encouraged by the fact that we are not able to detect resistance to Kaletra in patients who have no previous experience with HIV therapy."

Analyses of Drug Resistance At 108 Weeks of Kaletra Therapy

These results are also supported by similar analyses of an ongoing Phase II clinical trial in 100 patients new to HIV therapy after two years of treatment. In four patients who experienced viral rebound while on Kaletra (viral levels >400 copies/mL), genotypic and phenotypic resistance testing performed on viral samples detected no resistance to Kaletra.

Kaletra should not be used with certain medications. Taking certain other drugs with Kaletra could create the potential for serious side effects that could be life threatening. Patients should always talk to their physician or healthcare provider before starting new medicines. Kaletra should not be taken if a patient has had an allergic reaction to Kaletra or any of its ingredients. Cross resistance has been observed.

Increased bleeding in patients with hemophilia, and diabetes and high blood sugar have occurred in some patients when taking protease inhibitors. Changes in body fat have been seen in some patients receiving antiretroviral therapy. Some patients receiving Kaletra have had large increases in triglycerides and cholesterol. Pancreatitis and abnormal liver function have been reported in patients receiving Kaletra.

Kaletra is not a cure for HIV infection. People treated with Kaletra may continue to acquire illnesses associated with advanced HIV infection, including opportunistic infections. Kaletra has not been shown to reduce the risk of passing HIV to others through sexual contact or blood contamination. Patients should continue to practice safe sex and should not use or share dirty needles. The most commonly reported Kaletra-related side effects of moderate severity are: abdominal pain, abnormal stools, diarrhea, feeling weak/tired, headache, nausea and vomiting.

Under accelerated review, Kaletra was recently approved by the U.S. Food and Drug Administration (FDA) for marketing on Sept. 15, 2000, for use in combination with other antiretroviral agents for the treatment of HIV-infection. An application seeking approval is currently under review by the European Agency for the Evaluation of Medicinal Products (EMEA). Regulatory submissions for Kaletra are based on clinical data from studies conducted around the world, including 27 sites throughout Europe. Abbott also has submitted applications seeking marketing approval in Australia, Canada, Chile, Mexico, New Zealand, South Africa and Switzerland. Regulatory submissions in other countries will continue throughout the year.

Abbott has been providing Kaletra to patients in markets worldwide since the fall of 1999 through an Early Access Program. The Early Access Program gives patients who do not have other viable treatment options access to Kaletra.

The program was designed by working closely with key regulatory agencies and representatives of several HIV treatment organizations, and currently is available to more than 10,000 patients in 22 countries worldwide. Abbott's Early Access Program will continue to be available in many countries outside the United States.

Abbott Laboratories has been a leader in HIV/AIDS research since the early years of the epidemic. In 1985, the company developed the first licensed test to detect HIV antibodies in the blood, and remains the leader in HIV diagnostics. Abbott retroviral and hepatitis tests are used to screen more than half of the world's donated blood supply. With Kaletra, Abbott has developed two protease inhibitors, and also offers nutritional products that meet the unique dietary needs of people living with HIV.

Abbott Laboratories is a global, diversified health care company devoted to the discovery, development, manufacture and marketing of pharmaceutical, diagnostic, nutritional and hospital products. The company employs 58,000 people and markets its products in more than 130 countries.

Viracept(R) is a registered trademark of Agouron Pharmaceuticals, Inc.

SOURCE Abbott Laboratories Web Site: http://www.abbott.com Company News On Call: http://www.prnewswire.com/comp/110328.html or fax, 800-758-5804, ext. 110328

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