Healthcare payers may not be familiar with the high costs of paroxysmal nocturnal hemoglobinuria (PNH), or even know what it is, that is until the ultra-expensive drugs prescribed to treat this condition start showing up on claim reports. With a yearly cost of treatment reaching nearly $1MM, payers and patients alike need to be considered when developing a strategy for managing these drug treatments.
What Is Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare life-threatening disease with an estimated prevalence of between 10-16 cases per million in the United States. The disease may occur at any age but affects young adults preferentially. The diagnoses age for most patients ranges between 30 and 40 years while approximately 10% are diagnosed under 18 years of age. PNH is characterized by a gene mutation in the bone marrow stem cells leading to the destruction of red blood cells, blood clots, and impaired bone marrow function. PNH has a significant impact on the quality of life of the patients who suffer from it. The most common symptoms are pallor, fatigue, shortness of breath, dark urine, headaches, abdominal pain, unexplained bruising and bone marrow failure.
Cost of Care
After being introduced as the first drug on the market to treat PNH, Soliris was known as the “most expensive drug in the world” for nearly 10 years. Today, that same medication still ranks as the 10th most expensive drug in the world, despite having two new drugs to treat PNH enter the marketplace. The key difference here is that many of the drugs ranked on this list are primarily prescribed for short-term use, while the drugs used to treat PNH are lifelong treatments with costs accumulating year after year. With a total cost of care that can exceed $1 million dollars per patient per year, payers should peel back the layers to better understand PNH and the drugs used in the treatment of this high-cost condition.
The only cure for PNH is an allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, due to the high mortality rates associated with allo-HSCT, this treatment is usually reserved for those patients with serious complications such as severe bone marrow failure. In the past, treatment of PNH was mostly supportive and included frequent blood transfusions, iron supplementation, and anti-clotting medications with patients usually surviving for only 10 to 22 years after diagnosis. However, with the development of medications such as Soliris, the life expectancy of PNH patients is now similar to those without the disease.
Alexion Pharmaceuticals introduced Soliris to the market after gaining FDA approval in March 2007. The first-of-its-kind medication to treat patients with PNH, Soliris works by preventing the destruction of red blood cells resulting in a reduction in the need for blood transfusions as well as improvement of symptoms and overall quality of life. Soliris is an intravenously infused medication that can only be administered by a healthcare provider and is currently priced at $508,794 per year. Many patients require a maintenance dose every two weeks, resulting in frequent trips to an outpatient facility (i.e., hospital, doctor’s office, infusion center) or home visit from a provider for administration. Soliris also has FDA-approval for the treatment of hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD).
Alexion Pharmaceuticals’ second entry into the pharmaceutical market of treatments for PNH came in December 2018 with the FDA approval of Ultomiris. With less frequent dosing at every eight weeks, it has shown to be more cost-effective and have fewer breakthrough episodes of symptoms compared to Soliris. Just this past year, Ultomiris obtained the only FDA approval for treatment of pediatric patients with PNH, ages 1 month and greater, whereas Soliris is only approved for use in adults. By comparison, Ultomiris costs slightly less than Soliris at $457,886 per year but also requires administration by a healthcare provider which bears additional costs. Much like Soliris, Ultomiris has FDA approval for the treatment of hemolytic uremic syndrome (aHUS) and has ongoing clinical trials for other uses.
In May 2021, the FDA approved the third medication for treatment for adult patients with PNH, Apellis Pharmaceuticals’ Empaveli. It exhibits its effects in the body a little differently than both Soliris and Ultomiris. Empaveli is administered via a subcutaneous infusion which allows the medication to be self-administered by the patient, but requires dosing twice a week. At a price point just slightly higher than Ultomiris but less than Soliris, Empaveli costs $457,999 per year. When compared to Ultomiris and Soliris, the convenience of self-administration with Empaveli may be dampened by the inconvenience of more required doses. In head-to-head clinical trials Empaveli was shown better efficacy than Soliris in the treatment of patients with PNH. Also, a separate published study involving indirect comparison suggests patients who received Empaveli did better compared to patients who received Ultomiris.
Weighing All Factors
With three medication options now available for treatment of PNH, it seems that savings opportunities could emerge for healthcare payers, but at what cost to the patient? The price of the medication alone should not be the only consideration for payers when determining the most cost-effective strategy for managing drug treatment for patients suffering from PNH.
Some health plans and PBMs are requiring a trial of the less expensive Ultomiris prior to allowing use of Soliris, while others are treating them equally. The better patient outcomes with Empaveli, when compared to both Soliris and Ultomiris, should be factored in when making coverage decisions. Less favorable outcomes can lead to a higher overall total cost of care due to an increased need for transfusions and hospitalizations.
There are many other factors at play when comparing costs and efficacy of these treatments. Both Soliris and Ultomiris require infusion by a healthcare provider which means health plans will incur those additional administrative costs on top of the cost of the medication. The site of service can also impact the cost of care for PNH patients. Additionally, payers should be aware that some healthcare providers may choose to prescribe Ultomiris and Soliris versus the self-administered Empaveli to prevent reliance on patient adherence. Healthcare provider financial incentives may alter the drug selection, choosing the most profitable agent over a lower cost agent that will drive the same or better clinical outcome for the patient. Conversely, in the event Empaveli is not self-administered, the required twice weekly administrations are likely to add to the total cost of care if given by a healthcare provider.
Out of the three drugs currently available, there is no clear winner for payers to choose. The best strategy for managing drug spend in the treatment of PNH appears to be very patient dependent and payers should be prepared to individualize their strategy for each patient depending on where the drug can be given, and which agent can achieve the best outcomes.