Biotech Values

[DewDiligence]

Epzicom Comparable to Truvada in GSK Postmarketing Study

[In the treatment-naïve setting, each drug was added to Kaletra and the differences were inconsequential in terms of safety and efficacy. Nonetheless, it’s doubtful, IMO, that this study will do much to revive the commercial prospects for GSK’s Epzicom (a combination of Ziagen and Lamivudine, two older NRTI’s from GSK), which is getting badly beaten by GILD’s Truvada in the marketplace (#msg-26915314).

From a business standpoint, it would have been more meaningful for the common third drug in this study to be Sustiva or Reyataz—the two drugs most commonly given with Truvada—instead of Kaletra.]

http://biz.yahoo.com/prnews/080807/neth021a.html

›MEXICO CITY, Aug. 7 /PRNewswire-FirstCall/ -- GlaxoSmithKline (NYSE: GSK ) today announced that 96-week data from the HEAT study show that once-daily EPZICOM (abacavir + lamivudine) provides comparable efficacy to once-daily Truvada® (tenofovir DF + emtricitabine) as a first-line option for the treatment of HIV. The data were presented today at the 17th International AIDS Conference in Mexico City, Mexico.

HEAT is the first large, prospective, long-term, head-to-head trial to evaluate the safety and efficacy of EPZICOM and Truvada both combined with a boosted protease inhibitor (Kaletra) administered once-daily in adults who had no previous exposure to HIV medicines. The study involved 688 HIV therapy-naive patients: 343 randomized to treatment with EPZICOM and 345 randomized to treatment with Truvada.

Results of the study found that through 96 weeks efficacy endpoints for EPZICOM were comparable to Truvada, regardless of baseline viral load. At 96 weeks 60% of subjects receiving EPZICOM versus 58% of subjects receiving Truvada achieved a viral load <50 c/mL. Patients receiving EPZICOM also experienced similar median CD4+ cell increases to those patients receiving Truvada, 250 vs. 247. Overall, both regimens were generally well-tolerated with comparable safety profiles and few study discontinuations due to adverse events (6% for both treatment arms). Virologic failure occurred in 14% of patients for both groups.

"The result of the HEAT trial further demonstrates that EPZICOM is an effective first-line option for treatment-naive HIV patients with a well-established safety profile," said John Pottage, M.D., Vice President Global Clinical Development at GlaxoSmithKline. "This study provides the first, head-to-head, completed study comparing these two HIV treatments and demonstrates comparable results between the two."

Additionally, a review of two important inflammatory biomarkers, hs-CRP and IL-6, in the HEAT data set showed that levels of both biomarkers decreased from baseline at 48 weeks and 96 weeks. Further, there were no significant differences between EPZICOM and Truvada at any time points. Elevations of these markers have been associated with increased risk of cardiovascular events but the degree of association is still being evaluated.

HEAT Study Explained

HEAT is a head-to-head prospective, randomized, double-blind, placebo-matched, multicenter study evaluating the safety and efficacy of EPZICOM and Truvada. The study assigned 688 patients to receive either EPZICOM QD (n=343) or Truvada QD (n=345) both in combination with QD lopinavir/ritonavir. The primary efficacy endpoint was to determine the proportion of subjects with a viral load of <50 c/mL at 48 weeks and the primary safety endpoint was to evaluate safety and tolerability of both regimens at 96 weeks.

Results demonstrate that EPZICOM was comparable to Truvada in virologic and immunologic efficacy. At 48 weeks, 68% of subjects receiving EPZICOM versus 67% of subjects receiving Truvada achieved a viral load <50c/mL. At 96 weeks 60% of subjects receiving EPZICOM versus 58% of subjects receiving Truvada achieved a viral load <50c/mL. Of those patients who were able to achieve a viral load <50c/mL (ITT, M=F), both EPZICOM and Truvada saw similar success rates regardless of whether baseline viral load was <100,000c/mL (63% vs. 58%) or greater than or equal to 100,000c/mL (56% vs. 58%). Median CD4+ increase was comparable in both arms at week 96 (250 vs. 247).

Adverse events were similar in both arms. Both treatment arms had 6% of patients prematurely withdraw due to adverse events. In addition, 15% of patients had drug-related Grade 3-4 adverse events in both treatment arms. Patients receiving EPZICOM reported higher rates of suspected abacavir hypersensitivity reaction compared with Truvada (4% vs. <1%). Prospective HLA-B*5701 screening was not employed in this study. One percent of patients receiving Truvada developed proximal renal tubule dysfunction (vs. 0% for EPZICOM). Overall, treatment-limiting adverse events were comparable between the two arms.‹