Pivotal trial endpoints and prices of cancer drugs in the US and Europe.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2077-2077
Author(s):  
Kerstin Noëlle Vokinger ◽  
Paola Daniore ◽  
Thomas J Hwang ◽  
ChangWon C Lee ◽  
Aaron S Kesselheim
Keyword(s):  
Clinical Trial ◽  
Progression Free Survival ◽  
Treatment Costs ◽  
New Drugs ◽  
Cancer Drug ◽  
Pivotal Trial ◽  
Cancer Drugs ◽  
The Us ◽  
Trial Endpoints ◽  
Surrogate Measures

2077 Background: A key clinical outcome for new cancer drugs is improvement in overall survival (OS), defined as time from the date of randomization to the death from any cause. However, many cancer drugs are approved by regulators based on changes to surrogate measures of OS, such as progression-free survival or overall response rate. When surrogate measures are not validated, they can provide misleading information about drug efficacy. We categorized pivotal trial endpoints for recently-approved cancer drugs in the US and Europe as showing improvements in OS vs non-OS surrogates, and evaluated the correlation with drug prices. Methods: We identified new drugs FDA-approved between 2009 and 2018 that were indicated to treat solid and hematologic tumors in adults and that had also been approved by the EMA and Swissmedic by December 2019. Launch prices were extracted and adjusted to average sales prices for monthly treatment costs in the US and compared to currency-adjusted ex-factory monthly treatment costs in Germany, Switzerland, and England. Pivotal clinical trial primary endpoints were collected from the drug labeling and FDA medical reviews for the US, and the EMA public assessment reports for Europe, and categorized as OS in any trial vs. not. Pearson’s correlation tests assessed the association between launch prices and OS vs non-OS endpoints in each country. Results: 54 drugs were approved by the FDA, EMA, and Swissmedic during the study period. In the US, 30 (56%) were approved based on OS by contrast to 35 (65%) in the EMA. The number of cancer drugs approved by the FDA based on OS decreased in the past years. By contrast, the number of approved cancer drugs by the EMA based on OS were stable. There was no association for the US (p = 0.05), Germany (p = 0.13) and England (p = 0.12), while Switzerland revealed an association (p = 0.03) between OS endpoint and price. Conclusions: Reductions in use of OS endpoints as the basis for cancer drug approval in the US is concerning. Drug pricing should be better aligned with the benefit that drugs provide to patients, as measured by clinical trial outcomes such as OS.

Launch prices and price developments of cancer drugs in the United States and Europe.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2006-2006
Author(s):  
Kerstin Noëlle Vokinger ◽  
Paola Daniore ◽  
ChangWon C Lee ◽  
Aaron S Kesselheim ◽  
Thomas J Hwang
Keyword(s):  
Solid Tumors ◽  
The United States ◽  
Treatment Costs ◽  
Cancer Drug ◽  
Study Cohort ◽  
Cancer Drugs ◽  
Price Changes ◽  
Drug Prices ◽  
The Us ◽  
Over Time

2006 Background: Cancer drug costs are rising in the US and Europe. While drug manufacturers set prices without restriction in the US, European countries have regulations that allow national authorities to directly negotiate drug prices at launch and over time. We analyzed and compared the launch prices and price developments of cancer drugs in the US, Germany, Switzerland and England. Methods: We identified new drugs indicated to treat solid tumors in adults that were FDA-approved between 2009 and 2019 and had also been approved by the EMA and Swissmedic by 31 December 2019. Launch prices and post-launch price changes as of 1 January 2020 were extracted and adjusted to average sales prices for monthly treatment costs in the US and compared to comparable currency-adjusted ex-factory monthly treatment costs in Germany, Switzerland, and England. A cross-sectional analysis was conducted to infer yearly trends in launch prices and post-launch price changes across the countries. Results: The study cohort included 42 drugs for solid tumors, of which 40 (95%) drugs were first approved in the US compared to Germany and England, and 41 (98%) to Switzerland. Average launch prices for monthly treatment costs per patient were $15,178 in the US vs $7,049 in Germany, $7,421 in Switzerland and $8,176 in England, i.e., 215% (interquartile range [IQR] 263%-187%), 205% (IQR 202%-185%) and 186% (IQR 166%-189%) higher in the US compared to Germany, Switzerland and England respectively. Post-launch prices of 36 (86%), 40 (95%), and 38 (90%) drugs decreased over time with total savings of monthly treatment costs for all drugs in the study cohort of $86,744, $44,936, and $1744 in Germany, Switzerland, and England respectively. By contrast, prices of 8 (19%) drugs decreased, while 34 (81%) increased post-launch in the US with total additional expenses of $128,192 for monthly treatment costs. Conclusions: Launch prices for cancer drugs are far higher in the US than in Germany, Switzerland, or England. These price disparities continue to increase substantially after market entry since cancer drug prices, in general, decrease over time in Europe and increase in the US. Spending on cancer drugs could be reduced in the US if it adopted the principles used to more effectively negotiate drug prices in Europe.

Enrollment of Elderly Patients in Clinical Trials for Cancer Drug Registration: A 7-Year Experience by the US Food and Drug Administration

2004 ◽  
Vol 22 (22) ◽  
pp. 4626-4631 ◽  
Author(s):  
Lilia Talarico ◽  
Gang Chen ◽  
Richard Pazdur
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
The Elderly ◽  
New Drugs ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Age Related ◽  
The Us

Purpose To analyze the age-related enrollment of cancer patients onto registration trials of new drugs or new indications approved by the US Food and Drug Administration from 1995 to 2002. Patients and Methods This study involved retrospective analyses of demographic data of cancer patients enrolled onto registration trials. The data on 28,766 cancer patients from 55 registration trials were analyzed according to age distributions of ≥ 65, ≥ 70, and ≥ 75 years. The rates of enrollment in each age group for each cancer were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period 1995 to 1999 based on the 2000 US Census. Results The proportions of the overall patient populations aged ≥ 65, ≥ 70, and ≥ 75 years were 36%, 20%, and 9% compared with 60%, 46%, and 31%, respectively, in the US cancer population. Statistically significant under-representation of the elderly (P < .001) was noted in registration trials for all cancer treatment except for breast cancer hormonal therapies. Patients aged ≥ 70 years accounted for most of the under-representation. Conclusion Elderly were under-represented in the registration trials of new cancer therapies. Various strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in the elderly population.

Value appraisal of FDA approved cancer drugs over the past decade.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18385-e18385
Author(s):  
Ryan Huey ◽  
Seerat Anand ◽  
Jane Rogers ◽  
Arvind Dasari ◽  
Gauri Rajani Varadhachary ◽  
...  
Keyword(s):  
Health Care ◽  
Adverse Events ◽  
Drug Price ◽  
Progression Free Survival ◽  
New Drugs ◽  
Cancer Drug ◽  
Serious Adverse Events ◽  
Drug Regimens ◽  
Drug Approvals ◽  
Grade 3

e18385 Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.

Timing of US Food and Drug Administration (FDA) cancer drug approvals relative to publication of clinical trial results.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2071-2071 ◽  
Author(s):  
Ali Raza Khaki ◽  
Aakash Desai ◽  
Martin W. Schoen ◽  
Bishal Gyawali ◽  
Eddy J. Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Cancer Treatments ◽  
Fda Approval ◽  
Anti Cancer ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Clinical Trial Results ◽  
Careful Assessment

2071 Background: Publication of clinical trial results in peer reviewed literature is essential to inform clinicians regarding the use of new anti-cancer treatments, which often have a low therapeutic ratio and require careful assessment of risks and benefits. Publication of registration trials should precede FDA approval to facilitate evaluation and implementation of new therapies. The timing of trial publication relative to FDA drug approvals has not been systematically investigated. Methods: We collected all FDA drug approvals for a cancer indication between 2000-19. Trials were identified using FDA labels as well as drugs and publications indexed on HemOnc.org. Approvals for generics/biosimilars, non-oncology indications and label revisions without supportive evidence were excluded. Dates of approval, the approval pathway, approval type (new vs expansion), and the first full publication related to the registration were recorded. Trials and approvals were matched using available metadata. We calculated the proportion of drugs approved prior to publication overall and for those receiving accelerated approval (AA). We used logistic regression to compare rates of pre-publication approval by approval pathway and by new vs expanded approval. Results: Among a total of 378 drug approvals, 139 (37%) had pre-publication approval. Of these, the median overall time from approval to publication was 140 days (IQR 64-281 days). For those with approval after publication, median time from publication to approval was 157 days (IQR 72-359 days). The number of drugs approved pre-publication rose by 27% between the first and last quarters of the study period, though, the proportion decreased as more anti-cancer drugs have been approved in recent years (Table). More drugs were approved pre-publication through AA than regular approval (46% vs 34%, OR 1.66 [95% CI 1.03-2.70], p=0.04) and as new approvals vs. expanded approvals (45% vs 32%, OR 1.76 [95% CI 1.15-2.70], p=0.01). Conclusions: A substantial minority of FDA approvals occur before trial results are published, with the odds being higher for drugs receiving AA and for new approvals. Since clinicians rely upon published results to inform risk/benefit decisions, efforts are needed to ensure trial results are published by the time of FDA approval of new cancer drugs and indications. [Table: see text]

scholarly journals Trends of Business-to-Business Transactions to Develop Innovative Cancer Drugs

2020 ◽  
Vol 12 (14) ◽  
pp. 5535
Author(s):  
Arisa Djurian ◽  
Tomohiro Makino ◽  
Yeongjoo Lim ◽  
Shintaro Sengoku ◽  
Kota Kodama
Keyword(s):  
Small Molecules ◽  
Open Innovation ◽  
Business Environment ◽  
New Drugs ◽  
Cancer Drug ◽  
Annual Number ◽  
Pharmaceutical Companies ◽  
Cancer Drugs ◽  
Innovative Drug ◽  
Medical Needs

A key concept in the pharmaceutical industry is open innovation, in which pharmaceutical companies contribute to human health and adapt to a changing business environment by acquiring external knowledge. As successful drug discoveries and developments have become challenging, pharmaceutical companies must proactively pursue the open innovation of new drugs through various inter-firm partnerships to be more sustainable. This study aims to interpret the trend of inter-firm partnerships in the development of cancer drugs and to evaluate their effectiveness by examining inter-firm transactions related to cancer drugs approved by the US Food and Drug Administration (FDA). It is a novel approach to exercise this on each product instead of at the company level. The findings revealed that the number of inter-firm transactions in the oncology field has increased over the past 20 years. Furthermore, the annual number of transactions related to biologics has surpassed that of small molecules since 2015 and has been primarily driven by three PD-(L)1 inhibitors: Keytruda, Opdivo, and Tecentriq. Moreover, the average number of inter-firm transactions related to biologics is significantly higher than that of small molecules in total, in alliances, and in financing, suggesting that inter-firm transactions for biologic cancer drugs actively occur through various means. Additionally, a positive and significant correlation exists between the number of transactions and the average number of approved indications for biologics, but not for small molecules. These results suggest that the observed trend of active inter-firm transactions is key in increasing the probability of success in cancer drug research and development. This could provide a potential breakthrough in this industry for the successful development of innovative drug candidates to address unmet medical needs. Further study is necessary to confirm the applicability of this paradigm in broader drug discoveries and development.

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents

2019 ◽  
Vol 14 (2) ◽  
pp. 113-132 ◽  
Author(s):  
Elmira Ekinci ◽  
Sagar Rohondia ◽  
Raheel Khan ◽  
Qingping P. Dou
Keyword(s):  
Drug Resistance ◽  
Superoxide Dismutase ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Chronic Alcoholism ◽  
New Drugs ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Anti Cancer

Background:Despite years of success of most anti-cancer drugs, one of the major clinical problems is inherent and acquired resistance to these drugs. Overcoming the drug resistance or developing new drugs would offer promising strategies in cancer treatment. Disulfiram, a drug currently used in the treatment of chronic alcoholism, has been found to have anti-cancer activity.Objective:To summarize the anti-cancer effects of Disulfiram through a thorough patent review.Methods:This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy.Results:Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug.Conclusion:For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.

scholarly journals The UK Cancer Drugs Fund Experiment and the US Cancer Drug Cost Problem

2016 ◽  
Vol 91 (6) ◽  
pp. 707-712 ◽  
Author(s):  
Vinay Prasad ◽  
Sham Mailankody
Keyword(s):  
Drug Cost ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
The Us ◽  
The Uk

OP440 Comparison Of Evidence Supporting Cancer Drug Approvals And Prices In The US And Brazil

2021 ◽  
Vol 37 (S1) ◽  
pp. 16-17
Author(s):  
Adriana Ivama Brummell ◽  
Huseyin Naci
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Therapeutic Benefit ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Drug Benefits ◽  
Drug Prices ◽  
The Us ◽  
Drug Approvals ◽  
Overall Survival Benefit

IntroductionCancer drug prices are high on the policy agenda worldwide. Previous research found no association between cancer drug benefits and prices at the time of regulatory approval. Drugs approved in the US with uncertain benefits may have spill-over effects in other settings. Our objective was to compare the evidence supporting cancer drug approvals in the US and Brazil, and to examine the association between cancer drug prices and availability of added therapeutic benefit.MethodsWe matched all novel cancer drugs approved in the US from 2010–2019 to approvals in Brazil. We extracted data on pivotal study design characteristics and outcomes in the US and Brazil, and evidence supporting price approval in Brazil, including availability of added therapeutic benefit.ResultsFrom 2010–2019, fifty-six cancer drugs with matching indications were approved in US and Brazil and had their prices authorized in Brazil by December 2020. Drug were available in Brazil following a median 522 days after US approval (IQR: 351–932). In the US, thirty-four (60.7 percent) of the drugs had pivotal randomized controlled trials (RCTs) and Twelve (21.4 percent) had overall survival benefit. By the time of Brazilian approval, forty-one (73.2 percent) drugs had pivotal RCTs and twenty-two (39.3 percent) had overall survival benefit. A total of twenty-eight (50 percent) drugs did not demonstrate added therapeutic benefit over other authorized drugs for the same indication and had a median reduction from requested to approved price of 6.1 percent (IQR: 0–27.8 percent) in Brazil. The twenty-seven (48.2 percent) drugs with added therapeutic benefit had a median price reduction of 2.0 percent (IQR: 0–9.2 percent).ConclusionsHalf of new cancer drugs approved in Brazil failed to demonstrate added therapeutic benefit. The Brazilian pricing system secured considerable price reductions, ensuring that prices for medicines with no added therapeutic benefit were not higher than existing treatments for the same approved indication. Although evidence was more mature by the time of Brazilian review, pivotal studies often lacked randomization and overall survival endpoints.

Clinical benefit and prices of cancer drugs in the United States and Europe.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6638-6638 ◽  
Author(s):  
Kerstin Noëlle Vokinger ◽  
Thomas J Hwang ◽  
Ariadna Tibau Martorell ◽  
Thomas J Rosemann ◽  
Aaron S Kesselheim
Keyword(s):  
Clinical Benefit ◽  
Rating Scales ◽  
The United States ◽  
Drug Costs ◽  
European Countries ◽  
Cancer Drug ◽  
Study Cohort ◽  
Cancer Drugs ◽  
Drug Prices ◽  
The Us

6638 Background: Given rising cancer drug costs, Medicare recently proposed to tie some US drug prices to average prices paid by comparable countries. To understand the potential scope of this policy, we assessed differences in cancer drug prices in the US and selected European countries. We also evaluated the correlation between drug prices and their clinical benefit, as measured by two value frameworks: the American Society of Clinical Oncology Value Framework v2 (ASCO VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale v1.1 (ESMO-MCBS). Methods: We identified all new drugs for adult solid and hematologic cancers, approved by the FDA from 2009-2017 and that have also been approved by the EMA by December 31, 2018. US average sales prices (and if not available, wholesale acquisition costs) were extracted as of February 1, 2019, and compared to comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland. ASCO VF and ESMO-MCBS scores were assessed for pivotal trials supporting solid tumor drugs; in case of multiple trials, we focused on the highest score. Consistent with the developers of the rating scales, “high benefit” was defined as scores of A-B (neo/adjuvant setting) and 4-5 (palliative setting) on the ESMO-MCBS scale and scores≥45 on the ASCO VF. Linear regression models and non-parametric Kruskal-Wallis test and were used to assess the association between drug prices and benefit scores. Results: The study cohort included 63 drugs approved by the FDA and the EMA during the study period. 46 (73%) were approved for solid tumors, and 17 (27%) were approved for hematologic malignancies. Overall, median cancer drug prices in included European countries were 52% (interquartile range: 37-72%) lower than US prices. There was no statistically significant association between monthly treatment cost and ASCO-VF or ESMO-MCBS scores in any country. There was also no association between price differential between US and median European drug prices and either ASCO-VF (P = 0.599) or ESMO-MBCS (P = 0.321) scores. Conclusions: Cancer drug prices in the US were significantly higher than in the compared European countries. Drug prices of cancer drugs were not associated with clinical benefit in the US or in European countries.

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