A soaring price, a silent fight: Thioguanine portends new access barriers to life-saving treatments for children with cancer

Global access to cancer medicines is a well-documented barrier to care in low- and middle-income countries.^{1, 2} Availability, affordability, access, and pricing repeatedly arise as barriers internationally with wide variability between regions. In the United States, a 2021 cross-sectional study revealed disparities in access to pediatric cancer care along racial, ethnic, geographic, and socioeconomic groups.³ Additionally, chemotherapy drug shortages have continued to present a significant challenge to access for all,⁴ particularly for sterile injectable, generic products. In the year 2024, pediatric oncologists have been faced with a new barrier to access for an essential component of leukemia therapy.

Thioguanine was approved by the United States Food and Drug Administration in 1966 for remission induction and remission consolidation treatment of acute nonlymphocytic leukemias and has not changed since.⁵ In 1993, the Children's Cancer Group confirmed in a pivotal Phase III trial that the addition of a phase of care known as “Delayed Intensification (DI)” (inclusive of 2 weeks of thioguanine) significantly improved outcomes in acute lymphoblastic leukemia.⁶ Numerous large, cooperative group trials have since been published, which validate the importance of DI as a component of standard of care therapy for pediatric patients with acute lymphoblastic leukemia, which continues today.

Recently, thioguanine manufacturing was transitioned from West-Ward Pharmaceuticals PLC (now the Hikma Group) to Waylis Therapeutics LLC. In that transition, two things happened. One, the price per tablet (Tabloid®) increased by 20-fold. What used to cost an average of ∼800 US dollars per 2-week course is now averaging ∼17,000 USD. Second, Waylis has yet to enter Tabloid® into the Medicaid Prescription Drug Rebate Program. Without this step, state Medicaid officials cannot recognize Tabloid® as a covered entity. At the previous cost, exceptions to policy were routinely granted in the state of Iowa. However with current pricing, this is no longer possible. Instead, families are directed to Waylis’ patient access program, designed for patients without insurance or live at or below 500% of the current federal poverty level. Despite the burden and time of the paperwork, with adequate advanced planning, we have been able to secure thioguanine for all our patients. Unfortunately, some sites have informally reported thioguanine omission or substitution with mercaptopurine. Though this substitution is sensible, previous data from the Children's Oncology Group Phase III study CCG-1952 showed better EFS when thioguanine was used in maintenance when compared with mercaptopurine.⁷ Though this approach was abandoned due to toxicity, the study is added evidence that these two related medicines are not entirely equivalent. As the current thioguanine situation only impacts the publicly insured or uninsured, it serves as another potential disparity in access to standards of care for segments of the population.

Nothing to disclose relevant to this subject matter. I have served as a consultant for Tempus, Inc, Amgen, Day One Bio, and Y-mAbs Therapeutics, Inc.