Study Group: Bosentan Prescribers for PAH (US)

GLG News^SM Analyses by this Study Group's Leading Experts(?)

Oral Treprostinil: An effective medicine hiding in a study with a challenging design?

November 18, 2008

Analysis by:Robert Aris, Associate Professor of Medicine,

Analysis of:Freedom-C Trial of Oral Treprostinil in Pulmonary Arterial Hypertension Fails to Meet Primary Endpoint | ir.unither.com

This phase III study was done without the benefit of conventional drug development with Phase I and Phase II studies (which would have provided more information about the effective dose) preceding it because pharmacokinetic date from IV and SC dosing studies were used to extrapolate for the oral dosing. While in hindsight, this may have not been ideal, the trial holds a lot of promise that treprostinil will be effective since there was a nice dose-response curve and the higher doses clearly appeared to be effective. Oral Treprostinil is probably very similar to subcutaneous and intravenous prostanoids (remodulin and flolan) that require a slow uptitration of dose to allow the patient to become tolerant to the side effects. Thus having smaller doses for titration, which were available later in the trial, probably would have allowed for greater success had these doses been available earlier in the study.

Mild PAH improved by early treatment with bosentan

July 18, 2008

Analysis by:Robert Aris, Associate Professor of Medicine,

Analysis of:Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. | www.sciencedirect.com

While functional class II (FC II) PAH patients have been included in previous clinical trials, the EARLY trial is the first study to concentrate (ie recruit exclusively) FC II PAH patients.  This is important because the definition of functional class II is that a patient has a sight limitation in physical activity. Understanding "slight" is not so easy in clinical practice and there has been some reservation in treating "slightly" ill patients with very expensive drugs without better outcome studies in this target group. Thus the results of the EARLY study (Lancet June 2008) are welcome news to the PAH community.  Analyses were done with 168 patients and showed significant improvements in pulmonary vascular resistance and a strong trend (p = 0.075) toward improvement in 6 minute walk distance in bosentan-treated patients.  These results will certainly compell clinicians to treat patients with "slight" PAH more aggressively.

Peer reviewed literature on Ambrisentan, a selective ETRA for PAH

June 10, 2008

Analysis by:Robert Aris, Associate Professor of Medicine,

Analysis of:Ambrisentan for the Treatment of Pulmonary Arterial Hypertension | circ.ahajournals.org

This Circulation paper is the first peer reviewed data on the 2 pivotal Phase III trials on ambrisentan that lead the FDA to approving it for the treatment of PAH in July 2007. This paper is critically important since all new research needs to withstand the rigor of peer-review for physcians to fully embrace the findings.  And the journal Circulation is a top notch publication with "rigorous" reviewers.  Thus this publication will be well received by the PAH community and can be assimilated into the overall database of knowledge on PAH.

Exciting Prospect for Alternative Treatment of COPD and asthma

September 19, 2007

Analysis by:Warren Botnick, President,

Analysis of:Newly Discovered Fatty Acids May Lead To Novel Treatments For COPD And Asthma | www.medicalnewstoday.com

Eicosanoids appear promising in the treatment of such airways diseases as COPD and asthma, which affect millions worldwide.  Any alternative to current anti-inflammatory therapy, which consists almost entirely of forms of corticosteroids, would almost certainly be welcomed and adopted in widespread fashion.

Ceftobiprole for Community-Acquired Pneumonia is Breakthrough in Therapy

September 19, 2007

Analysis by:Warren Botnick, President,

Analysis of:Basilea Announces Positive Top-line Data from Phase III Study of Ceftobiprole in Community-acquired Pneumonia Requiring Hospitalization | www.pipelinereview.com

Cephalosporins have been standard therapy for pneumonia for many years, but to date this class of drug has been ineffective against MRSA.  Ceftobiprole appears to represent a breakthrough in this regard.  I would expect the drug to be well tolerated and, for the most part, to cause few major adverse effects.  However, the use of ceftriaxone as a comparator is odd, as this would not be used as monotherapy by most physicians in the USA for patients with CAP who are sick enough to warrant hospital admission.

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