Tyrosine kinase inhibitors (TKIs) have radically improved the treatment of chronic myeloid leukemia (CML), a rare myeloproliferative disease defined by the excessive production of myeloid cells, both mature and immature, in the bone marrow, blood, and spleen [1]. CML has three phases, namely the chronic phase (CP), accelerated phase (AP), and the blast phase (BP). In greater than 90% of CML cases, diagnosis is made during the CP; if untreated CML will progress into the initial AP and thereafter to the more aggressive BP [1]. Widespread and successful use of TKIs has resulted in an increased number of CML patients surviving with a near-normal life expectancy, subsequently increasing the prevalence of this disease [2]. The ultimate goal of CML treatment is normal survival and good quality of life without lifelong treatment. In resource-poor developing countries, the unavailability of effective drugs and limited essential monitoring systems result in the goal of treatment remaining as survival [3].
The treatment of CML with TKIs therapy attracts high costs coupled with recommended lifelong therapy [4], which translates to a significant burden on health care systems. In South Africa (SA) there are three active pharmaceutical ingredients of cellular TKIs registered by the South African Health Products Regulatory Authority (SAHPRA); namely Imatinib, Dasatinib, and Nilotinib [5]. All three TKIs are available in the private health sector whereas only two TKIs (Imatinib and Nilotinib) are available on tender in the public health sector [6]. Access to TKIs significantly impacts the management of CML. Therefore, only two TKIs for CML treatment are readily available in the SA public sector.
The SA access to TKIs has increased through patient assistance programs and clinical trials. Patient assistance programs such as the Glivec International Patient Assistance Program (GIPAP), which was set up as a partnership between Novartis and The Max Foundation in 2002, have supplied Imatinib at no cost to poorer patients [7, 8]. The two organizations collaborated to ensure that patients with CML or Gastrointestinal Stromal Tumor (GIST) received treatment. The GIPAP was a direct-to-patient access program introduced after Novartis recognized the impact that Glivec had on CML and GIST. Novartis assumed responsibility of managing the supply chain for the medicine and interacted with local stakeholders such as physicians, pharmacists, treatment centers, non-governmental organizations (NGOs), private companies, and governments (in countries where it operated) whilst The Max Foundation provided psychosocial support and education.
In 2017, it was reported that since the inception of GIPAP, the program had served the CML treatment needs of approximately 75,000 patients [8]. Over time, Novartis and The Max Foundation recognized a more flexible approach to treatment access was needed, which led to a new collaboration in 2017 called the CMLPath to Care™ that replaced GIPAP. Under the new collaboration, The Max Foundation was responsible for supply chain management and treatment delivery to patients, whilst Novartis provides funding and medicine donation support. CMLPath to Care™ aims to support continued access to treatment at no cost for the nearly 34 000 previously registered patients in GIPAP with CML, GIST, and other rare cancers that responded to Imatinib. The program has been reported to run in 68 countries in the following regions: East Asia, Pacific, Europe, Central Asia, Latin America, Caribbean, Middle East, North Africa, South Asia, and Sub-Saharan Africa [9].
Due to TKIs use and the subsequent improved global CML survival rates, there has been an increase in the prevalence of CML [2]. The 2040 prevalence of CML has been estimated to be 250 000 patients in the United States of America (USA) due to the success of Imatinib increasing survival [10]. As TKI treatment attracts a high cost and against a backdrop of recommended lifelong therapy [4], this can translate to a significant burden on healthcare systems. A systematic review that focused on the economic burden associated with CML treatment in the United States noted that CML poses a significant economic burden influenced by prescriptions, inpatient and outpatient costs, adherence and costs related to adverse events, switching between medications, and treatment failure [11]. As per the European LeukemiaNet (ELN), the ultimate goal of CML treatment is normal survival and good quality of life without lifelong treatment. However, in resource-poor countries, which are affected by the unavailability of effective drugs and limited essential monitoring, the goal of treatment remains as survival [12].
Aim and objectives
The aim was to compare the cost profiles of TKIs registered in SA for the treatment of CML.
To achieve this, the following specific objectives were outlined: