Myogen Reports Positive Top Line Results for Ambrisentan LFT Rescue Study In Pulmonary Arterial Hypertension
Monday February 13, 8:30 am ET
Patients with PAH Who Previously Discontinued Other ERA Therapy Due to Liver Function Abnormalities Treated with Long-term Ambrisentan Therapy
DENVER, Feb. 13 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG - News) today announced positive top line results of the AMB-222 study, an open-label study of ambrisentan in patients with pulmonary arterial hypertension (PAH) who have previously discontinued bosentan and/or sitaxsentan treatment due to liver function abnormalities. None of the 36 patients enrolled in the study had a recurrence of liver function abnormalities that resulted in discontinuation of ambrisentan during the initial 12-week evaluation period (the primary endpoint of the study). One patient had a transient serum aminotransferase test result greater than three-times the upper limit of the normal range (3xULN) at week 12 that resulted in dose reduction from 5 mg to 2.5 mg ambrisentan. This patient remains on ambrisentan therapy and has not had a recurrence of serum aminotransferases greater than 3xULN. Patients have continued to receive ambrisentan therapy for periods up to 9 months (mean exposure of 6 months) and no further occurrence of serum aminotransferase concentrations greater than 3xULN has been observed.
"These results suggest that for patients who have had to stop treatment with other endothelin receptor antagonists due to liver function abnormalities, ambrisentan may offer an opportunity to resume treatment," stated Michael J. Gerber, MD, Senior Vice President of Clinical Development and Regulatory Affairs for Myogen. "I believe ambrisentan has the potential to be an important therapeutic option for these patients with PAH and their physicians. The low incidence and severity of liver function test abnormalities demonstrated in the ARIES-2 trial and the AMB-222 rescue study are very encouraging. Ambrisentan has a chemical structure that differs from those of bosentan and sitaxsentan. We believe that this distinction may underlie ambrisentan's low propensity to cause liver function abnormalities."
Myogen announced the initiation of AMB-222 in May 2005 with a target enrollment of 30 patients. A total of 36 patients were enrolled in the study, of which 31 (86%) had discontinued bosentan, 2 (6%) had discontinued sitaxsentan and 3 (8%) had discontinued both bosentan and sitaxsentan, sequentially, due to serum aminotransferase abnormalities. Also, 17 (47%) of the patients were receiving concomitant sildenafil therapy. Patients received 2.5 mg of ambrisentan once daily for 4 weeks and then the dose was increased to 5 mg of ambrisentan once daily. The last patient reached the 12-week endpoint evaluation in January 2006. All patients had the option to continue ambrisentan therapy after the initial 12-week assessment period.
The primary endpoint of the trial was the incidence of serum aminotransferase concentrations greater than 3xULN during the 12-week evaluation period that were related to ambrisentan and resulted in discontinuation of drug.
The top line results of the ARIES-2 and AMB-222 trials, as well as the results to date of Myogen's Phase 2 trial of ambrisentan in PAH (AMB-220) and related long-term study (AMB-220-E) have demonstrated:
* Improvement in exercise capacity that is significant, early in onset and
durable
* Significant improvement in time to clinical worsening
* Comparable benefit in exercise capacity for patients with WHO functional
class II and class III symptoms
* An apparent survival benefit when compared with predicted survival based
on the National Institutes of Health Registry formula
* Effectiveness with once-daily dosing and the potential for dose
flexibility
* Low incidence and severity of liver function test abnormalities at all
doses
* Potential utility in resuming endothelin receptor antagonist (ERA)
treatment in patients who have discontinued bosentan or sitaxsentan
treatment due to liver function abnormalities
* No apparent drug-drug interactions with warfarin-type anticoagulants
Based on results to date and the properties of ambrisentan, Myogen believes that, if ambrisentan is ultimately approved, it may offer significant clinical benefit to PAH patients not provided by other PAH therapies. |
