Atlantic Study Positions ZERIT(R) (d4T, Stavudine) and Once-Daily VIDEX(R) (ddI, didanosine) as Flexible, First-Line Foundation of HIV 'Cocktails'

SAN FRANCISCO (PROTEXT) - Landmark International Treatment'Strategy' Trial Results Provide Patients and Doctors ImportantNews on Customizing Treatment With Three Types of Anti- HIVCocktails According to preliminary 48-week data from the ATLANTIC study,the nucleoside analogue foundation of ZERIT(R) (d4T, stavudine)and once-daily VIDEX(R) (ddI, didanosine) with the addition of adrug from any one of three commonly used classes of drugs hasproduced highly potent results. In August, the U.S. Food and DrugAdministration (FDA) approved ZERIT and VIDEX for use as a first-line component of a triple combination antiretroviral therapyregimen. In June, once-daily VIDEX received mutual recognition bythe member states of the European Union. Results of the ATLANTIC study, the first international studyto determine how to best start and sequence HIV drug regimens,show that the third drug -- a non-nucleoside reversetranscriptase inhibitor (nevirapine), a protease-inhibitor(indinavir) or another nucleoside analogue (lamivudine) -- can betailored to meet patients' specific medical needs, allowingphysicians and patients to preserve future treatment options. "The ATLANTIC study results clearly suggest that physiciansand patients can safely start anti-HIV therapy with a variety ofthree-drug combinations, " said Robert Murphy, MD, professor ofmedicine, medical director of the AIDS Clinic Treatment Unit,Northwestern University Medical School and a leading investigatorof the ATLANTIC study. "These 48 week results reaffirm theability of physicians to customize therapy for individualpatients and save certain treatment options for future use -- animportant consideration as treatment guidelines continue toevolve." Preliminary (48 week) results from the ATLANTIC trial showthat the addition of nevirapine, indinavir or lamivudine to theZERIT(R) (d4T, stavudine) / VIDEX(R) (ddI, didanosine) foundationproduced sustained reductions in viral load (a measure of theamount of HIV in the blood) and increases in CD4+ cell counts.Previous studies, notably the ALBI study and the START II trials,have shown that the ZERIT/VIDEX foundation is at least as potentand tolerable as the dualnucleoside combination of AZT/3TC, andassociated with greater increases in CD4 cell counts.Additionally, ZERIT/VIDEX foundation has a more favorableresistance profile. The median increase of CD4 cells at week 48 was 146 ford4T/ddI/IDV, 134 for d4T/ddI/NVP, and 166 for d4T/ddI/3TC. Themajority of patients on all three arms were able to sustain viralreductions of <50 copies/ml through week 48.

d4T/ddI/3TC

d4T/ddI/NVP d4T/ddI/IDV Intention-to-treat

49%

51%

57% As-treated

78%

82%

90% "Intention-to-treat" analyses all patients who entered thetrial. "As treated" analyses only those patients who werecurrently on the study's therapies at 48 weeks. ATLANTIC is a randomized, open-label, strategy study designedto evaluate the safety and efficacy of three available triplecombination regimens in patients who have not previously receivedtreatment. The study includes over 300 patients at 17 sites inEurope and the United States treated with the combination ofZERIT (40 mg) and once daily VIDEX (400 mg) combined withnevirapine, indinavir or lamivudine. Patients will be followed for up to 144 weeks, making ATLANTICthe longest trial ever to measure efficacy of triple combinationregimens. Patients with a moderately increased viral load(between 500 and 5,000 copies/ml) will intensify their treatmentwith the addition to the anti-cancer agent hydroxyurea to theirregimen. It is anticipated that this approach may delay the needfor patients to switch to a new combination regimen. Strategy trials are studies designed to evaluate realistictreatment regimens as a means to determine what drugs to startwith, when to switch regimens and what drugs to switch to. Suchtrials view HIV as a chronic disease that requires optimalmanagement over the long term. Historically, HIV clinical trialshave been designed to measure the efficacy of specific drugcombinations, comparing single agents to double combinations, ordouble combinations to triple combinations. Such trials did notaddress the differences between commonly used triplecombinations. "Patients beginning HIV-therapy need to get the best startthey can and they need therapies that continue to work overtime," said Steve Schnittman, MD, Group Director, HIV ClinicalResearch, Bristol-Myers Squibb. "These updated results from theATLANTIC study demonstrate the treatment options that arepossible with ZERIT and VIDEX and the durability of combinationsbased on ZERIT and VIDEX." Patients in each of the ATLANTIC study arms received a once-daily dose of VIDEX(R) (ddI, didanosine) (400 mg), which iscurrently in clinical trials worldwide. Once daily dosing isthought to make it easier for patients to adhere to their drugregimens, as incomplete adherence may lead to the development ofdrug resistance, thereby reducing the ability of treatmentregimens to keep HIV at bay. Bristol-Myers Squibb is a diversified worldwide health andpersonal care company whose principal businesses arepharmaceuticals, consumer products, nutritionals, and medicaldevices. It is a leading maker of innovative therapies forcardiovascular, metabolic and infectious diseases, centralnervous system and dermatological disorders, and cancer. Thecompany is also a leader in consumer medicines, orthopaedicdevices, ostomy care, wound management, nutritional supplements,infant formulas, and hair and skin care products. Visit Bristol-Myers Squibb on the World Wide Web athttp://www.bms.com. For full prescribing information on ZERIT andVIDEX, please contact Patti Duquette at 1-609-897-3077. otsOriginal Text Service: Bristol-Myers Squibb International LimitedInternet: http://www.newsaktuell.de Contact: Patricia DoykosDuquette of Bristol-Myers Squibb, International Public Affairs,415-284-8043, e-mail: patricia.duquette@bms.com; or Glenn Mursellof Countrywide Porter Novelli, +44-171-584-0122 email:glenn.mursell@cpn.co.uk Web site: http://bms.com

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