HIV-Associated Wasting or Cachexia

The clinical efficacy of SEROSTIM in HIV-associated wasting or cachexia was assessed in two placebo-controlled trials. All study subjects received concomitant antiretroviral therapy. There was no increase in the incidence of Kaposi's sarcoma (KS), lymphoma, or in the progression of cutaneous Kaposi's sarcoma in clinical studies of SEROSTIM. Patients with internal KS lesions were excluded from the studies. Potential effects on other malignancies are unknown.

Clinical Trial 1:

A 12-week, randomized, double-blind, placebo-controlled study followed by an open-label extension phase enrolled 178 patients with severe HIV wasting taking nucleoside analogue therapy (pre-HAART era). The primary endpoint was body weight. Body composition was assessed using dual energy X-ray absorptiometry (DXA) and physical function was assessed by treadmill exercise testing. Patients meeting the inclusion/exclusion criteria were treated with either placebo or SEROSTIM 0.1 mg/kg daily. Ninety-six percent (96%) were male. The average baseline CD4 count/microliter was 85. The results from one hundred forty (140) evaluable patients were analyzed (those completing the 12-week course of treatment and who were at least 80% compliant with study drug). After 12 weeks of therapy, the mean difference in weight increase between the SEROSTIM-treated group and the placebo-treated group was 1.6 kg (3.5 lb). Mean difference in lean body mass (LBM) change between the SEROSTIM-treated group and the placebo-treated group was 3.1 kg (6.8 lbs) as measured by DXA. Mean increase in weight and LBM, and mean decrease in body fat, were significantly greater in the SEROSTIM-treated group than in the placebo group (p=0.011, p<0.001, p<0.001, respectively) after 12 weeks of treatment (Figure 1). There were no significant changes with continued treatment beyond 12 weeks suggesting that the original gains of weight and LBM were maintained (Figure 1).

Treatment with SEROSTIM resulted in a significant increase in physical function as assessed by treadmill exercise testing. The median treadmill work output increased by 13% (p=0.039) at 12 weeks in the group receiving SEROSTIM (Figure 2). There was no improvement in the placebo-treated group at 12 weeks. Changes in treadmill performance were significantly correlated with changes in LBM.

Figure 1: Mean Changes in Body Composition

Figure 2: Median Treadmill Work Output

Clinical Trial 2:

A 12-week, randomized, double-blind, placebo-controlled study enrolled 757 patients with HIV-associated wasting, or cachexia. The primary efficacy endpoint was physical function as measured by cycle ergometry work output. Body composition was assessed using bioelectrical impedance spectroscopy (BIS) and also by dual energy X-ray absorptiometry (DXA) at a subset of centers. Patients meeting the inclusion/exclusion criteria were treated with either placebo, approximately 0.1 mg/kg every other day (qod) of SEROSTIM, or approximately 0.1 mg/kg daily at bedtime of SEROSTIM. All results were analyzed in intent-to-treat populations (for cycle ergometry work output, n=670). Ninety-one percent (91%) were male and 88% were on HAART anti-retroviral therapy. The average baseline CD4 count/µL was 446. Six hundred forty-six patients (646) completed the 12-week study and continued in the SEROSTIM treatment extension phase of the trial.

Clinical Trial 2 results are summarized in Tables 4 and 5:

The mean maximum cycle work output until exhaustion increased after 12 weeks by 2.57 kilojoules (kJ) in the SEROSTIM 0.1 mg/kg daily group (p<0.01) and by 2.53 kJ in the SEROSTIM 0.1 mg/kg every other day group (p<0.01) compared with placebo (Table 4). Cycle work output improved approximately 9% in both active treatment arms and decreased <1% in the placebo group. Lean body mass (LBM) and body weight (BW) increased, and fat mass decreased, in a dose-related fashion after treatment with SEROSTIMand placebo (Table 5). The LBM results obtained by BIS were confirmed with DXA.

Patients' perceptions of the impact of 12 weeks of treatment on their wasting symptoms as assessed by the Bristol-Meyers Anorexia/Cachexia Recovery Instrument improved with both doses of SEROSTIMin Clinical Trial 2.

Extension Phase: All patients (n=646) completing the 12-week placebo-controlled phase of Clinical Trial 2 continued SEROSTIM treatment into an extension phase. Five hundred and forty eight of these patients completed an additional 12 weeks of active treatment. In these patients, changes in cycle ergometry work output, LBM, BW, and fat mass either improved further or were maintained with continued SEROSTIM treatment.