Costly New Drugs Could Lead to Generation of Have-Nots in CLL

The kinase inhibitors ibrutinib and idelalisib have the potential to dramatically improve outcomes in patients with chronic lymphocytic leukemia (CLL), but out-of-pocket costs under Medicare Part D and the societal costs of providing such treatments could place them out of reach for many, according to a study published in the Journal of Oncology Practice.

The study by Mayo Clinic researchers compared the costs of traditional therapies with the use of ibrutinib (Imbruvica, Janssen) and idelalisib (Zydelig, Gilead) on a hypothetical patient population created from preexisting CLL patient data from Olmsted County, Minnesota. Three scenarios were considered: available treatment before approval of ibrutinib and idelalisib (historical scenario), using ibrutinib and idelalisib as salvage therapy, and assuming use of ibrutinib as first-line treatment (potential future scenario). Both drugs were approved for CLL treatment in 2014.

Cost estimates for patients newly diagnosed with CLL under Medicare Part D ranged from $325 per treated patient over a 10-year period for traditional medicine to $35,564 under the first-line scenario. The 10-year overall pharmaceutical cost estimate for traditional therapy was $157,446 per treated patient and $566,002 per treated patient under the frontline scenario, the report stated.

“Although ibrutinib and idelalisib are profound treatment advances, they will dramatically increase individual out-of-pocket and societal costs of caring for patients with CLL,” the report stated. “These cost considerations may undermine the potential promise of these agents by limiting access and reducing adherence.”

The report was released at the same time as two congressmen introduced a bill to moderate the cost-sharing requirements for patients as newer targeted therapies improve outcomes, but come with high price tags.

The Patients’ Access to Treatments Act as introduced in the House would “make critical, life-saving medications—some of which can cost thousands of dollars per month—affordable for patients. Instead of paying a percentage of the cost of these drugs, from 25% to 33% or more, patients would have a much lower, fixed co-payment,” according to a statement from the American Society of Hematology.

“The advent of powerful, targeted therapies over the last several decades has revolutionized care for blood diseases such as leukemia, multiple myeloma, and hemophilia,” the society said in the statement. Additionally, it said patients are often delaying or forgoing treatment to avoid having to pay, resulting in long-term health complications. The bill was introduced by Representatives David McKinley (R-WV) and Lois Capps (D-CA).

The Mayo study noted that CLL is the most common form of leukemia, affecting some 150,000 people in the United States, with an additional 16,000 diagnosed yearly.

“Approximately 70% of patients with CLL eventually require treatment. Once patients with CLL require therapy, they frequently relapse and need multiple treatments to control their disease,” the report said.

The traditional treatment for CLL was oral chlorambucil. It was comparatively inexpensive at $3500 for 6 cycles of treatment but was “relatively ineffective” with a complete remission rate of approximately 5% and a median progression-free survival (PFS) of approximately 1 year, the report stated.

The report said more recent chemoimmunotherapy regimens, which combine purine analog and alkylator-based chemotherapy with monoclonal antibodies, have improved response rates, PFS, and overall survival (OS).

These regimens have achieved a median PFS of approximately 5 years, at a cost of $60,000 to $100,000 for 6 cycles, the report said. Most treatment costs for CLL are borne by Medicare because the median age at diagnosis is about 70 years.

However, ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase, has shown very strong results in salvage therapy and as a first-line treatment for patients with CLL, the report said.

The first reported trial of ibrutinib in CLL enrolled 85 patients with heavily pretreated relapsed or refractory disease. Approximately 90% of patients had evidence of response, with PFS and OS rates after 26 months of continuous therapy of approximately 75% and 83%, respectively, the report stated.

It said a “pivotal trial” of idelalisib in patients who had major comorbidities to rituximab found that idelalisib improved not only the overall response rate, but also PFS and OS (12-month OS, 92% vs 80%; P = .02).

Treatment with ibrutinib or idelalisib requires continuous daily use and the current average wholesale price of these drugs in the United States is approximately $118,000 per year, the report said.

It went on to estimate that the cost of treating the 16,000 people diagnosed each year with CLL represents a societal cost of $730.5 million under traditional therapy and substantially more with the newer treatments. Second-line therapy with ibrutinib could cost $1.25 billion in this example, whereas second-line therapy with idelalisib could cost $1 billion, the report said.

Using ibrutinib as a first-line therapy could cost $2.6 billion, the authors wrote.

The authors called upon oncologists to join the fight to achieve lower pricing of drugs and especially novel therapies in the United States, noting that US consumers sometimes pay two to three times the price of drugs in other developed countries.

“If this trend continues, cost—rather than science—may become the greatest barrier to effective treatment of malignancy in the United States and could result in two classes of medical citizenship,” the report said.

Shanafelt TD, Borah BJ, Finnes HD, et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels [published online March 24, 2015]. J Clin Pract. doi:10.1200/JOP.2014.002469