Encouraging 48-Week Protease Inhibitor Resistance Data Presented for Abbott Laboratories' Kaletra(TM) (Lopinavir/Ritonavir) in Patients Without Previous HIV Therapy

ABBOTT PARK, Ill., Feb. 7 /PRNewswire/ -- Data presented at a scientific meeting in Chicago from a 48-week study of patients new to HIV therapy showed that of those who experienced viral rebound (HIV RNA >400 copies/mL), no patient (0/31) treated with a Kaletra-based regimen was found to have protease inhibitor-resistant HIV by genotypic analysis compared to 32 percent (21/65) of patients treated with a nelfinavir-based regimen.

Furthermore, resistance to the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine (3TC) was seen less often in patients who had viral rebound on the Kaletra-based regimen than those on the nelfinavir-based regimen. Genotypic testing examines a viral sample for specific mutations, or changes, in the virus that are known to cause resistance to certain drugs.

"Although resistance may be observed with longer study of Kaletra, these 48-week data regarding PI resistance in naive patients beginning combination therapy with Kaletra are encouraging," said Eugene Sun, M.D., head of antiviral drug development at Abbott Laboratories.

Study M98-863 is a randomized, double-blind, Phase III study of 653 HIV treatment-naive patients treated with either Kaletra (N=326) or nelfinavir (N=327), in combination with stavudine (d4T) and 3TC. Patients with detectable HIV (>400 copies/mL) at either Week 24 or Week 48 were identified (42 patients in the Kaletra arm, 78 patients in the nelfinavir arm), and their viruses examined for evidence of HIV drug resistance.

Of the viruses that could be analyzed, none (0/31) from patients in the Kaletra arm had protease inhibitor resistance, compared to 32 percent (21/65) from patients in the nelfinavir arm. Additionally, resistance to 3TC was detected in 42 percent of viruses (13/31) from patients in the Kaletra arm, compared to 86 percent of viruses (56/65) from patients in the nelfinavir arm.

In a separate study of viral isolates from 56 patients who had not taken Kaletra and had previous experience with at least two protease inhibitors, cross resistance was evaluated between lopinavir and other protease inhibitors. An analysis demonstrated that viruses with reduced susceptibility to lopinavir were more likely to maintain susceptibility to amprenavir and saquinavir, than to the other protease inhibitors, ritonavir and indinavir. Additionally, an analysis of isolates from five single or multiple PI- experienced patients who had viral rebound while taking a Kaletra regimen and developed increased resistance to lopinavir, showed that HIV with decreased susceptibility to lopinavir had, at most, only modestly-reduced susceptibility to amprenavir. Viral isolates from three saquinavir-naive patients with decreased susceptibility to lopinavir maintained susceptibility to saquinavir.

"The findings in this study of experienced patients suggest a different resistance pattern between lopinavir and amprenavir or saquinavir," added Sun. "Further investigation is underway to evaluate these findings clinically by studying amprenavir- and saquinavir-based regimens in patients who have failed Kaletra therapy."

In the United States, Kaletra is indicated in combination with other antiretroviral agents for the treatment of HIV-infection. This indication is based on analyses of plasma HIV RNA levels and CD4 cell counts in a controlled study of Kaletra of 24 weeks duration, and in smaller open-label studies of Kaletra of 72 weeks 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 clinical progression of HIV.

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 to other protease inhibitors 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. In adults, 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 approved for marketing by the U.S. FDA on Sept. 15, 2000. Abbott also has obtained marketing approval in Argentina, Brazil, Chile, Colombia, Dominican Republic, Guatemala, India, Japan, Mexico, Peru, Switzerland, and Uruguay. In December, the Committee for Proprietary Medicinal Products (CPMP) issued a positive opinion for Kaletra in the European Union. Abbott has submitted applications seeking marketing approval in numerous other countries, and additional approvals of Kaletra are anticipated throughout 2001.

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 this treatment. Kaletra will continue to be available through Abbott's Early Access Program in countries outside the United States where it is pending local regulatory approval and market availability.

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 60,000 people and markets its products in more than 130 countries.

Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com . SOURCE Abbott Laboratories

CONTACT: U.S. Media, Cindy Resman, 847-935-9545, or Jennifer Smoter, 847-935-8865, Media Outside U.S., Laureen Cassidy, 847-938-7743, Financial Community, John Thomas, 847-938-2655, all of Abbott Laboratories/