Oral trepsostinil (Remodulin) approved by FDA

Update on PAH TreatmentsAfter more than seven years of development and clinical trials, United Therapeutics received approval from the FDA on 12/20/2013 for their oral version of treprostinil (Remodulin).  The new drug will be called Orenitram.  Orenitram has had a bumpy course with three major trials completed and reported and only one of them positive.  The manufacturer has several ongoing studies to determine how to best use this medication.  In the positive study, Orenitram was compared to placebo in untreated patients.  Orenitram improved exercise capacity at the end of 16 weeks.

What does this mean for patients?

First, a new treatment option is always good news.  However, this medication will be very complicated to use properly.  It may be dosed two or three times daily with more recent studies using the three times daily dosing regimen.  In patients who have never been exposed to Remodulin, the medication has a substantial side effect burden.  Even at low doses, patients experience nausea, vomiting, headache, diarrhea, abdominal cramps, flushing and muscle aches.  The medication is started at a very low dose and then gradually increased over time.  In order to benefit from the medication, the dose must be increased.  When you look at the three completed studies, patients that achieved a dose of 4mg twice (or three times) daily by the end of 16 weeks had much better results.

One very exciting way of using Orenitram is in patients that have been on continuous Remodulin (IV or Subcutaneously) and have had a good response.  There is an ongoing study that is looking at switching such patients.

How will I use Orenitram?

Even though this medication showed very mild efficacy as single agent therapy in PAH patients not treated with other medications, I don’t think this is the optimal patient population.  I think that in patients that are doing very well but have more room to improve this medication may well have a role.  I am very excited about the prospect of being able to switch some patients from intravenous/subcutaneous Remodulin to the pill form.

Be careful!

Just being on a low dose of this medication is not enough.  If you and your doctor are not able to increase the dose over time then you may not benefit at all from this medication.  Over time we will learn more precisely what the dosing targets should be.  My read of the published literature suggests that at least 4mg three times daily is the absolute minimum dose that should be targeted by the end of six months and that by the end of the first year, perhaps 5-6 mg three times daily.

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