Which Key Attributes Will Drive Physician Prescribing and Formulary Inclusion of Current and Emerging PAH Therapies?

Pulmonary arterial hypertension (PAH) is a severe, progressive, debilitating disease marked by considerable morbidity and mortality. Existing PAH drugs increase the expected life span of PAH patients, but clinicians continue to seek novel but safe therapies that can further increase life expectancy, exercise capacity, and time to clinical worsening. There is also an increasing focus on “harder” end points in clinical trials of potential PAH therapies. Following the launch of several agents for PAH in the last few years, the market is becoming increasingly competitive, a status that is expected to continue with the anticipated approval and launch of selexipag in late 2015 and the growing trend toward the use of combination therapy earlier in the treatment algorithm.

Questions Answered in This Report:

  • A drug’s performance on at least five efficacy end points, including effect on long-term survival and change in exercise capacity, is important for drug approval and physician use. What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European pulmonologists weight efficacy measures and other drug attributes in their prescribing decisions for PAH?

  • Greater increases in long-term survival, greater improvements in time to clinical worsening, and greater improvements in quality of life are key areas of unmet need in PAH, according to the insights of surveyed U.S. and European pulmonologists. Which therapies in development for PAH are poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome in order to capitalize on these areas of unmet need? What degree of improvement over currently available therapies do surveyed U.S. MCO PDs seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?

  • Mortality rate at one year and change in exercise capacity are key drivers of physicians’ prescribing decisions and/or the focus of drug development in PAH. What trade-offs across these and other clinical attributes are U.S. pulmonologists willing to make when considering the use of emerging therapies for the treatment of PAH? Based on the trade-offs in price and performance across key drug attributes that U.S. pulmonologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for PAH?

  • Based on its clinical profile, macitentan (Actelion/Nippon Shinyaku’s Opsumit) is the current clinical gold standard in our Drug Comparator Model. What attributes do thought leaders believe differentiate this therapy from competing current therapies and emerging therapies? Will any therapies in development challenge macitentan as the future gold standard in 2018 or 2023?


Attributes included in conjoint analysis-based assessment of target product profiles for PA:

- Mortality rate at one year.

- Change in exercise capacity (6MWD at 16 weeks).

- Incidence of clinical worsening at 16 weeks.

- Risk of severe adverse events.

- Risk of gastrointestinal side effects.

- Frequency of administration.

- Price per day of therapy.

Attributes included in assessment of U.S. payers’ receptivity to new therapies for PAH:

- Effect on mortality rate at one year.

- Efficacy in improving exercise capacity at 16 weeks.

- Effect on incidence of clinical worsening.

- Risk of severe adverse events (including hepatic function abnormalities and bleeding).

Physicians surveyed: 60 U.S. and 30 European pulmonologists.

Payers surveyed: 20 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Bosentan (Actelion’s Tracleer)

- Sildenafil (Pfizer’s Revatio, generics)

- Macitentan (Actelion/Nippon Shinyaku’s Opsumit)

- Epoprostenol (GlaxoSmithKline/Gilead Science’s Flolan, generics)

- Inhaled treprostinil (United Therapeutics’ Tyvaso)

Emerging Therapies

- Selexipag (Actelion/Nippon Shinyaku’s Uptravi)

- Ambrisentan and tadalafil combination (Gilead Science’s Letairis/GlaxoSmithKline’s Volibris and Eli Lilly/United Therapeutics/Nippon Shinyaku’s Adcirca)

- Oral treprostinil (United Therapeutics’ Orenitram)

- Imatinib (Novartis Gleevec/Glivec)

- INOpulse nitric oxide (Bellerophon Therapeutics)

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