AbbVie updated markets via PR NewsWire on its RESOLVE (PCYC-1137) trial which evaluated ibrutinib in combination with chemotherapy agents nab-paclitaxel and gemcitabine versus placebo in combination with the chemotherapy agents. The commercial sponsor reports that the study did not show statistically-significant progression-free or overall survival benefit with ibrutinib in combination versus the placebo combination study arm. AbbVie has been testing Imbruvica to treat metastatic pancreatic cancer, one of the most aggressive and deadly forms of cancer, with an estimated 5-year survival of less than 5%.
What is ibrutinib? A small molecule drug, it permanently binds to a protein called Bruton’s Tyrosine Kinase (BTK)—important in B cells, which are utilized to treat B cell cancers such as mantle cell lymphoma, chronic lymphocytic leukemia, and Waldeynström’s macroglobulinemia. As reported in Wikipedia, it was created by scientists at Celera Genomics as a tool compound for studying BTK function, then developed by Pharmacyclics up to Phase II—at which time Johnson and Johnson became a partner. In 2015, AbbVie acquired Pharmacyclics. Imbruvica is jointly developed with both AbbVie and Janssen (J&J). Certain studies that included Ibrutinib (Imbruvica) indicate higher CLL survival rates.
Imbruvica has been approved by the FDA in six disease areas with nine treatment indications and has cumulatively treated more than 135,000 patients globally in clinical practice and trials. Sales of Imbruvica grow at a healthy pace—at the end of quarter 1 2018, the company reported $762 million for one quarter—making it a billion dollar plus drug in 2018. AbbVie itself has projected Imbruvica sales will peak at $7 billion.
- It was first approved for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in November 2013.
- Thereafter it was initially approved in adult chronic lymphocytic leukemia (CLL) patients who have received at least one prior therapy in February 2014.
- By summer of 2014, it was approved for adult CLL patients with 17p deletion, and by March 2016 it was approved as a frontline CLL treatment.
- In January 2015 it was approved to treat adult patients with Waldenström’s Macroglobulinemia (WM).
- In May 2016 it was approved in combination with bendamustine and rituximab (BR) for adult patients with CLL/small lymphocytic lymphoma (SLL)
- By January 2017, it was approved for adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy
- In August 2017, IMBRUVICA was approved for adult patients with chronic graft versus host disease (cGVHD) that failed to respond to one or more lines of systemic therapy.
- In August 2018, IMBRUVICA plus rituximab was approved for adult patients with WM.
As the intensive approval timeline evidences, Imbruvica has clearly helped many patients in dire situations.
As reported by GoodRx the drug on average costs $13,093.82 per each bottle (90 capsules at 140mg). The average cost of Imbruvica is the U.S. equals $148,000 per annum. To introduce a “flat pricing structure” in the first half of 2018, Pharmacyclics and Janssen introduced a single dose tablet formulation and discontinued the capsule formulation. This caused an outcry as it was perceived to triple the cost of the drug to the average patient. Patients receiving the FDA approved and recommended doses would have seen either no price change or a price decrease with the tablet pricing structure. Since then they have reversed course and offer both capsule and tablet forms. In 2018 the treatment was included in the Australian Pharmaceutical Benefits Scheme.
In a 2016 Stat News analysis of leukemia drug prices, Ed Silverman reported that the increasingly high prices of some leukemia drugs will make them less cost-effective. Imbruvica was included in the analysis. Researchers published a warning in the Journal of Clinical Oncology that “oral targeted therapies will increase survival rates substantially. However, with the current price structure, they will dramatically increase the cost of CLL management for both patients and payers.”
In 2018, it was reported in Cancer Therapy Advisor that Ibrutinib (Imbruvica) was deemed not cost-effective by the prominent ICER standards. It was reported that “Ibrutinib is not a cost-effective therapeutic option per quality-adjusted-life-year (QALY) among patients with chronic lymphocytic leukemia (CLL) compared with a comparator, according to a study published in Blood Advances.” The article’s writer, James Nam, noted the powerful contribution of Bruton’s tyrosine kinase inhibitors (TKI) to “greatly improved survival outcomes in CLL.” But when payer-driven direct pharmacoeconomic studies have yet to be applied comparing ibrutinib and available first line therapies. The actual study Nam referred to was titled “Cost-effectiveness of ibrutinib as first-line therapy for chronic lymphocytic leukemia in older adults without deletion 17p and can be referred to here.
TrialSite News surveyed some other links and resources for pharmacoeconomic stances on Imbruvica.
In Ireland the National Center for Pharmacoeconomics reports that the cost effectiveness of ibrutinib (Imbruvica®) in the treatment of patients with CLL who have received ≥1 prior therapy, or as a first-line treatment in the presence of del(17p)/TP53 mutation in patients not suitable for chemo-immunotherapy, has not been demonstrated and therefore it is not recommended for reimbursement at the submitted price.
In the Netherlands (where currently Ibrutinib is not reimbursed) Erasmus University Rotterdam thesis from Robert Molthof produced a report entitled “Economic Evaluation of Ibrutinib as First-Line Treatment of Unfit Patients with Chronic Lymphocytic Leukemia in the Netherlands and the Potential Role of Precision Medicine.” The summary of this pharmacoeconomic analysis is that Ibrutinib for previously untreated and unfit CLL patients in the Netherlands is not a cost-effective strategy compared to the standard treatment of GClb when an €80,000 ICER threshold is used.
In Canada the CADTH Pan-Canadian Oncology Drug Review (pCODR) was established by Canada’s provincial and territorial Ministries of Health to assess cancer drug therapies and make recommendations to guide drug reimbursement decisions. In November, 2016 its pCDOR Expert Review Committee (pERC) recommended reimbursement of Imbruvica as an option for the treatment of patients with previously untreated CLL or SLL conditional on the cost effectiveness being approved to an acceptable level. On the other hand, in another academic study sponsored in party by manufacturer Janssen, the results demonstrate that Ibrutinib is cost-effective and greatly improves long-term health outcomes over current treatments in a hard to treat population.
The evidence is clear that Imbruvica makes a difference in a number of deadly cancers. It can extend life which for the patient and their loved ones is in reality priceless. However, economics comes into play. If payers don’t cover the cost, the price is out of the reach of most patients worldwide. The more the manufacturer can demonstrate the pharmacoeconomic benefits, the better for securing coverage by payers.