Archive for December, 2010

United Therapeutics’ Oral Treprostinil (UT-15C SR) – can it expand the treprostinil franchise to patients with milder disease?

Posted by lifetech on December 10th, 2010

Pulmonary arterial hypertension (PAH) is a rare disease, but it has nevertheless drawn significant interest from the biotech industry. Since 2001, FDA has approved six new agents from three different drug classes to treat PAH, dramatically improving patient outcomes for this serious and progressive disease. The next frontier consists of bringing the best treatment options to patients with less severe disease. Unfortunately, prostacyclins (the class considered to be the most efficacious) only exist in parenteral infusions or inhalable forms which deter their adoption among patients with milder disease – who obviously prefer the convenience of oral treatments.

United Therapeutics is working diligently towards developing an oral version of its successful prostacyclin analog – treprostinil – already available in IV, SC and inhalable versions. Oral treprostinil could significantly expand the market opportunity for the franchise. But the process of reaching adequate blood levels with oral delivery has posed some challenges. Aggressive dose titration led to the failure of UT-15C SR’s first phase III trial: many patients dropped out and few were able to escalate dose to therapeutic levels. The company has since developed lower strength tablets and two new studies are underway evaluating the “lower start /slow increase” approach. Favorably, the company states that drop-out rates in the ongoing trials are considerably lower. We can interpret this in two ways: first, it could be a sign that the gradual approach has indeed improved UT-15C SR’s tolerability and that patients can escalate to the therapeutic dose levels. But second, it could also mean that patients are using much lower doses; in which case the gain in tolerability may come at the expense of efficacy. Only the former interpretation bodes well for the outcome of ongoing trials. But meeting the primary endpoint in phase III may not be enough to ensure commercial success, given the competing treatment options already available. In our UT-15C SR report, we review the evidence to handicap the likelihood that ongoing trials will succeed, and discuss the commercial implications and market opportunity for UT-15C SR.