Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration

Abstract

Background The clinical benefit and pricing of breakthrough‐designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough‐designated and non–breakthrough‐designated cancer drug approvals. Methods A cross‐sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017. For each indication, the clinical benefit from the pivotal trials was scored via validated frameworks: the American Society of Clinical Oncology Value Framework (ASCO‐VF), the American Society of Clinical Oncology Cancer Research Committee (ASCO‐CRC), the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO‐MCBS), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks. A high clinical benefit was defined as scores ≥ 45 for the ASCO‐VF, overall survival gains ≥ 2.5 months or progression‐free survival gains ≥ 3 months for all cancer types for the ASCO‐CRC criteria, a grade of A or B for trials of curative intent and a grade of 4 or 5 for trials of noncurative intent for the ESMO‐MCBS, and scores of 4 and 5 and a combined score ≥ 16 for the NCCN Evidence Blocks. Monthly Medicare drug prices were calculated with Medicare prices and DrugAbacus. Results This study identified 106 trials supporting approval of 52 drugs for 96 indications. Forty percent of these indications received the breakthrough designation. Among the included trials, 33 (43%), 46 (73%), 35 (34%), and 67 (69%) met the thresholds established by the ASCO‐VF, ASCO‐CRC, ESMO‐MCBS, and NCCN, respectively. In the metastatic setting, there were higher odds of clinically meaningful grades in trials supporting breakthrough drugs with the ASCO‐VF (odds ratio [OR], 3.69; P = .022) and the NCCN Evidence Blocks (OR, 5.80; P = .003) but not with the ASCO‐CRC (OR, 3.54; P = .11) or version 1.1 (v1.1) of the ESMO‐MCBS (OR, 1.22; P = .70). The median costs of breakthrough therapy drugs were significantly higher than those of nonbreakthrough therapies (P = .001). Conclusions In advanced solid cancers, drugs that received the breakthrough therapy designation were more likely than nonbreakthrough therapy drugs to be scored as providing a high clinical benefit with the ASCO‐VF and the NCCN Evidence Blocks but not with the ESMO‐MCBS v1.1 or the ASCO‐CRC scale.

Association between FDA and EMA expedited approval programs and therapeutic value of new medicines: retrospective cohort study

“…The study findings, which are consistent with a previous study of FDA designated breakthrough cancer drugs and an analysis stratifying new drug approvals by novelty of mechanism of action,242526 suggest a widening gap between regulatory approval and the clinical and public health priorities of health systems, payers, and patients after approval. Contributing to this may be the varying quality of clinical trial evidence available at the time of approval and resulting uncertainty around the extent of clinical benefit 272829.…”

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications

“…Having said this, Salas-Vega in their analysis found that 43% of new oncology medicines approved either by the FDA or the European Medicines Agency (EMA) between 2003 and 2013, and subsequently reviewed by health technology agencies, did improve overall survival by 3 months or longer [72]. In addition, as mentioned, Molto et al (2020) found that 40% of new treatments recently received a breakthrough therapy designation, and were more likely than non-breakthrough therapies to provide a high clinical benefit [10]. Consequently, minimum thresholds of three to six months are likely to remain.…”

“…However, there are concerns with reimbursed prices for new oncology medicines, especially among higher-income countries and the actual level of health gain seen [8,9]. However, Molto et al (2020) found that 40% of new oncology medicines recently received a breakthrough therapy designation, and were more likely than non-breakthrough therapies to provide a meaningful clinical benefit [10]. In addition, Lauenroth et al (2020) found that the reforms in Germany led to reimbursed prices for new oncology medicines falling following evaluation; subsequently, more in line with the clinical benefit seen [11].…”

The value of new drugs for advanced prostate cancer

“…Antineoplastic drugs account for a large and growing share of drugs in development and new drug approvals 1 . Most are approved on the basis of randomized trials, yet the value of new drugs in a real‐world setting remains unclear 2 . Drugs tested in phase 3 trials must demonstrate a clinical benefit over the control‐arm therapy.…”

“…1 Most are approved on the basis of randomized trials, yet the value of new drugs in a real-world setting remains unclear. 2 Drugs tested in phase 3 trials must demonstrate a clinical benefit over the control-arm therapy. However, the comparator may not always reflect the most recent treatment available to patients at the time the drug is approved because of the long duration of oncology clinical trials, especially when multiple drugs come to market at the same time.…”