The increased number of available United States Food and Drug Administration (FDA)-approved drugs indicated for acute myeloid leukemia (AML) have generated considerable interest and may have the potential to influence practice. We performed a retrospective cross-sectional study performed from September to November 2019 to determine 1) demographic and subgroup characteristics of patients with newly diagnosed cases of acute myeloid leukemia, 2) FDA data on drugs indicated for AML approved from 1969 through November 2019, 3) measures of response from drug labels, and 4) published reports documenting the response for drugs approved before the 1979 Labeling Act. We used publicly available data from the Food and Drug Administration (FDA), the American Cancer Society, the Leukemia and Lymphoma Society, and the U.S. Census Bureau. According to our estimation methods, cytarabine infused continuously for 7 days, with three short boluses of anthracycline over Days 1-3, the standard of care known as "7 + 3", continues to have the largest population benefit. The maximum cost per course of treatment for an average regimen is enasidenib for salvage therapy, estimated to be around $120,131. The minimum cost was $1,662.50 for standard 7 + 3 chemotherapy. The mean and median cost for all AML treatments was $43,784.26 and $35,083.70, respectively. While it is true that the number of available therapies approved by the FDA has increased dramatically, it is not yet clear how large of a clinical benefit we can expect to see from these new lines of therapies.

Objective

To examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020.

Design, setting and participants

Retrospective cross-sectional study included 194 pivotal trials supporting cancer drug approvals by the US FDA from 2015 to 2020.

Interventions

Clinical trials were analysed for the type of blinding, primary endpoint, whether crossover was specified in the publication, study phase, line of therapy, response rate, investigational sites, manufacturer and randomisation ratio.

Main outcome measures

The main outcome was the rate of accrual, which is the number of patients accrued in the study per open month of enrolment.

Results

The study consisted of 133 randomised (68%) and 61 (32%) non-randomised clinical trials. In randomised studies, we found the accrual rate was higher in trials investigating first and second line drugs (adjusted rate ratios (aRR): 1.55, 95% CI 1.18 to 2.09), phase III trials (aRR: 2.13, 95% CI 1.48 to 2.99), and for studies sponsored by Merck (aRR: 1.47, 95% CI 1.18 to 2.37), adjusting for other covariates. In contrast, the primary endpoint of a study, presence of crossover, single agent response rate, the number of investigational sites, population disease burden and skewed randomisation ratios were not associated with the rate of accrual. In the non-randomised adjusted model, the accrual rate was 2.03 higher (95% CI 1.10 to 3.92) for clinical trials sponsored by manufacturer, specifically Merck. Primary endpoint, crossover, trial phase, response rate, the number of investigational sites, disease burden or line of therapy were not associated with the rate of accrual.

Conclusion

In this cross-sectional study, line of therapy, study phase and manufacturer were the only factors associated with accrual rate. These findings suggest many proffered factors for speedy trial accrual are not associated with greater enrolment rates.

Importance

The growth of cancer drug spending in the US has outpaced spending in nearly all other sectors, and an increasing proportion of the drug development pipeline is devoted to oncology. In 2018, there was a record number of drugs entering the US market.

Objective

To estimate the number of patients with cancer who are eligible for the newly approved drug-indication pairs, and project potential spending and use of the approvals in the US.

Design, setting, participants

This is a retrospective review of 2018 US Food and Drug Administration (FDA) oncology drug approvals with estimation of the eligible population. The cost of new therapy was estimated, and savings from displaced therapies were subtracted. Two-way sensitivity analysis explored uncertainty in pricing and market diffusion. Data were collected between March 1, 2019, and September 30, 2019.

Exposures

Data related to the cancer drug approval (ie, indications, approval pathway, basis for approval), cancer incidence, and drug price were extracted from publicly available sources, including the FDA, National Cancer Institute, and American Cancer Society websites, as well as the RED BOOK database.

Main outcomes and measures

The primary outcome was the projected net expenditure in the US associated with the new therapies. The secondary outcome described how variable market diffusion and pricing permit expected levels of spending.

Results

A total of 46 oncology approvals were included in the analysis, with 17 novel drugs and 29 new indications. The average price per patient per treatment course was $150 384. From a national perspective and with 100% market diffusion, the projected net expenditure for newly approved drugs was $39.5 billion per year. To maintain the recent trend of cancer drug spending, the 2018 cancer drug approvals need to be used in fewer than 20% of eligible patients.

Conclusions and relevance

New cancer drugs approved by the FDA in 2018 would drastically increase cancer drug spending in the US if used widely. Alternatively, only low-level use of the new drugs is consistent with market forecasting.

This cross-sectional study estimates all US Food and Drug Administration anticancer approvals in recent years and evaluates if an association exists between their cost and efficacy.

Importance

Many economic theories point to regulatory issues and subsidization of research and development costs as the primary factor in the high cancer drug prices in the US. Even so, the association between the median annual cost and novelty of cancer drugs approved in the US remains unclear.

Objective

To evaluate the association between the median annual cost and novelty of cancer drugs approved in the US over a 6-year period.

Design, setting, and participants

This cross-sectional study included all cancer drugs approved by the US Food and Drug Administration (FDA) from January 1, 2015, to December 31, 2020. Drug names, indications, manufacturer, dosage, and measures of activity/efficacy were extracted from the FDA announcement. The search was performed in December 2021. Data were analyzed from January 2022 until April 2022.

Main outcomes and measures

Annual cost of treatment was calculated based on average wholesale price collected from the 2021 Micromedex Red Book database. Mechanism of action was inferred from trial publication or its references.

Results

There were 224 cancer drug approvals across 119 individual drugs, with a median annual cost of $196 000 (IQR, $170 000-$277 000). Gene and viral therapies were the most expensive (median, $448 000 [IQR, $448 000-$479 000]), followed by small molecule therapy (median, $244 000 [IQR, $203 000-$321 000), and biologics (median, $185 000 [IQR, $148 000-$195 000]). There was no significant difference in cost between first-in-class, next-in-class, and subsequent approvals of an already approved drug.

Conclusions and relevance

Findings of this study indicate that the median annual price of anticancer drugs in the US is not associated with the novelty of their mechanism of action.