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Displaying One Session
- William K. Evans (Hamilton, Ontario, Canada)
- Aris Angelis (London, United Kingdom)
- Tit Albreht (Ljubljana, Slovenia)
Open & welcome
1585MO - Factors associated with change in overall survival and quality of life between time of approval and post-marketing among anti-cancer therapies
- Aida Bujosa RodrÃguez (Barcelona, Spain)
Abstract
Background
The US Food and Drug Administration (FDA) criteria for registration allow cancer drugs to be approved based on surrogate outcomes. Here, we explore factors associated with overall survival (OS) and quality of life (QoL) benefit both at the time of initial approval and in the post-marketing period (PMP).
Methods
For trials supporting FDA cancer drug approvals between January 2006 and December 2015, we performed a systematic search of Pubmed and ClinicalTrials.gov to identify updated OS and/or QoL data, with follow-up through to April 2019. We explored variables associated with improvement in OS or QoL in the palliative setting using logistic regression.
Results
Among 96 trials, approval was based on improved OS in 41%. Among 59 trials providing updated efficacy data in the PMP, 47% showed improved OS; 39% for the first time. Improved OS at any time was observed in 52% of all trials. Only 47% of trials reported patient-reported outcomes (PRO) initially. Of these, 58% demonstrated a significant improvement in at least one PRO. Among 50% of trials which reported updated PRO data, improved QoL was observed in 46%; 50% for the first time. Improved QoL was observed in 38% of all trials. There were statistically significant associations between improved OS at initial approval and regular approval (OR 21.38; p=0.004), orphan drug designation (OR 0.39; p=0.04), sample size (OR 1.70; p<0.001), most prevalent tumors (OR 2.40; p=0.041), and crossover (OR 0.16; p=0.001). There was a non-significant association between improved QoL at initial approval and open-label studies (OR 3.85; p=0.053). Improved OS in the PMP was associated with immunotherapy (OR 8.20; p=0.026) and drugs with companion diagnostics (OR 11.67; p=0.006). Improved QoL in PMP was associated with sample size (OR 0.73; p=0.031), immunotherapy (OR 9.14; p=0.02) and open-label studies (OR 8.89; p=0.048).
Conclusions
Factors associated with OS and QoL benefit differs at the time of approval and in the PMP. Initially, drugs for prevalent tumors with regular approval are associated with OS benefit. In the PMP, immunotherapy and drugs with companion diagnostic tests are associated with improved OS.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.C. Tapia: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Grünenthal Group. A. Barnadas: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Genomic Health International. E. Amir: Speaker Bureau/Expert testimony: Genentech/Roche; Honoraria (self): Apobiologix; Honoraria (self): Agendia; Honoraria (self): Myriad Genetics; Honoraria (self): Sandoz. A. Tibau: Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Genentech/Roche; Travel/Accommodation/Expenses: Ipsen; Honoraria (self): Eisai. All other authors have declared no conflicts of interest.
1586MO - Pivotal trial endpoints of drugs for rare and non-rare cancers in the US and Europe
- Kerstin N. Vokinger (Zurich, Switzerland)
Abstract
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. Surrogate endpoints, such as progression-free survival or overall response rate, can provide misleading information about efficacy. However, for rare cancers, as outlined by Rare Cancers Europe (RCE), a campaign developed by ESMO, surrogate endpoints may be of value or even the only way to show improvements timely. Furthermore, the FDA and EMA introduced orphan drug designation to encourage drug development for rare conditions. We categorized pivotal trial endpoints for approved cancer drugs by the FDA and EMA (OS vs. OS surrogates) and evaluated the correlation with orphan drug designations by the FDA and EMA as well as rare cancers as defined by the RCE.
Methods
We identified new cancer drugs FDA-approved between 2009 and 2019 that were indicated to treat solid and hematologic tumors in adults and that had also been approved by the EMA by December 2019. Fisher’s exact tests were conducted to assess the association between pivotal trial endpoints (OS vs. non-OS) and orphan drug designation by the FDA and EMA, as well as between pivotal trial endpoints and rare cancers as defined by RCE.
Results
76 drugs were approved by the FDA and EMA during the study period. In the US, 39 (51%) were approved based on OS by contrast to 49 (64%) in the EU; 50 (66%) drugs were designated orphan status by the FDA, 17 (22%) by the EMA. There was an association between rare cancers as defined by the RCE and drug indications designated with orphan status by the FDA (p=0.007) or EMA (p<0.001). However, there was no association between pivotal trial endpoints (OS vs. non-OS) and orphan drug designation by the FDA (p=0.094) or EMA (p>0.9). There was also no association between rare cancers as defined by the RCE and pivotal trial endpoints (p=0.2 [US] and p=0.3 [EU]).
Conclusions
Approval of drugs for non-rare cancers should be better aligned with OS as pivotal trial endpoint. Since surrogate measures may not be adequately predictive of patient-centred outcomes, cancer drugs approved based on surrogate endpoints should be closely followed up also after approval to offer patients optimal value.
Legal entity responsible for the study
K.N. Vokinger.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 1585MO and 1586MO_PR
1587MO - How much does it cost to research and develop a new medicine? A systematic review and evaluation of 40 years of literature
- Karla Hernandez Villafuerte (Heidelberg, Germany)
Abstract
Background
The biopharmaceutical industry faces challenges related to its research & development (R&D) productivity. At the same time, some pricing policies for new products, particularly those concerning anticancer and orphan medicinal products, have been perceived as non-transparent or even outrageous, resulting in increased resistance by policy makers to reimburse them. In this context, a controversial theme has been the cost of bringing a new molecular entity (NME) to market. We reviewed, and critically assessed, the studies providing estimates of the pre-launch research & development (R&D) cost per NME.
Methods
A full systematic literature review of publications estimating the (pre-launch) R&D costs was conducted. 22 articles with 45 cost estimates were included (three focus on oncology and 16 include cancer alongside other therapeutic areas). We appraised their quality by evaluating 16 factors covering three domains: (1) how the drug samples, success rates, and development times used for cost estimation were obtained; (2) potential sources attributing to the variation in R&D costs; and (3) the cost components.
Results
Estimates of the total average capitalized R&D costs vary widely, from $161million to $4,539 million (2019 USD), with cancer drugs marking the top. We found evidence that the magnitude of these estimates has increased over time, but it is not related to study quality. In addition, average costs mask important differences, e.g. estimations suggested positive skewness for oncological drugs, with an average capitalized R&D cost between $944 and $4,539 million, while a median between $788 and $2,818 million (2019 USD). “Potential sources of variation” was the domain that shows the lowest quality scores.
Conclusions
Due to the heterogeneity of the methodologies and the variability (e.g., by therapeutic area) of the results, caution must be exercised when applying the estimated R&D cost averages. Given the variability of pre-launch drug R&D cost estimates, a standardized framework specifying the factors that ought to be considered in cost estimation seems warranted, and we propose one such here.
Legal entity responsible for the study
German Cancer Research Center (DKFZ).
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
1588MO_PR - A comparative study on costs of cancer and access to medicines in Europe
- Nils Wilking (Stockholm, Sweden)
Abstract
Background
Costs and value of new cancer treatments are often causing headlines without being discussed in a larger context. This study estimates the cost of cancer and access to medicines in Europe in 2018 and extends a previous analysis for 1995–2014.
Methods
Cancer-specific health expenditure for 31 countries (EU-27 plus Iceland, Norway, Switzerland, and the UK) were derived from national estimates. Data on cancer drug sales were obtained from IQVIA. Productivity loss from premature mortality was estimated from data from Eurostat and the WHO. Productivity loss from morbidity and informal care costs were estimated based on previous studies.
Results
The total cost of cancer was €199 billion in 2018. Total costs ranged from €160 per capita in Romania to €578 in Switzerland (after adjustment for price differentials). Health expenditure on cancer care were €103 billion, of which €32 billion were spent on cancer drugs. Informal care costs were €26 billion. The total productivity loss was €70 billion, composed of €50 billion from premature mortality and €20 billion from morbidity. Patient access to cancer medicines was much greater in wealthier than poorer countries in 2018, in terms of value and volume. The top spenders were Austria, Germany, and Switzerland (€92 to €108 per capita), whereas Czechia, Latvia, and Poland spent the least (€13 to €16). The largest country differences were seen in immuno-oncology medicines. Between 1995 and 2018, cancer incidence increased by 50% in Europe, but cancer mortality increased only by 20%. Health spending on cancer doubled from €52 billion to €103 billion (in 2018 prices and exchange rates), but the share of cancer care on the total health expenditure remained stable at around 4–7%. A shift from treatment in inpatient care to ambulatory care has likely saved costs. Expenditure on cancer medicines tripled from €10 billion to €32 billion between 2005 and 2018 (excluding confidential rebates). Productivity loss from premature mortality decreased over time, linked to mortality reductions in working-age patients.
Conclusions
There are large and persistent country differences in spending on cancer care, access to new cancer medicines and outcomes in Europe. Inequalities are mainly related to countries’ economic strength and not to the disease burden of cancer.
Legal entity responsible for the study
The Swedish Institute for Health Economics, Lund, Sweden.
Funding
European Federation of Pharmaceutical Industries and Associations (EFPIA), Brussels, Belgium (unrestricted grant).
Disclosure
N. Wilking: Advisory/Consultancy, This study has been supported by an unrestricted grant from EFPIA: Bayer, BMS, EFPIA, Eisai, Oasmia, Roche, Sanofi. G. Brådvik; P. Lindgren; C. Svedman: Advisory/Consultancy, IHE conducts research and evaluations for a large number of for-profit health care companies: IHE and EFPIA (unrestricted grant). B. Jönsson: Advisory/Consultancy, IHE and EFPIA (unrestricted grant): Bayer, BMS, AZ, Allergan, Celgene, Jansen, Takeda, Vifor, Pfizer, Novartis. T. Hofmarcher: Advisory/Consultancy, IHE conducts research and evaluations for a large number of for-profit health care companies: IHE and EFPIA (unrestricted grant).
Invited Discussant 1587MO and 1588MO
1589MO - Opposition to a patent covering tisagenlecleucel: Using intellectual property (IP) legislation to defend sustainable access to cancer therapies
- Juliana Veras (Paris, France)
Abstract
Background
Since 2013, cancer care professionals have raised concerns about cancer treatment high prices. As prices on cell therapies have skyrocketed over $350,000, there is now a consensus that cancer drugs’ high prices may become a barrier to universal access to new cancer therapy, and to the sustainability of public health systems. High prices on new cancer drugs are linked to monopolies, misuse of patents and lack of public scrutiny regarding the quality of patents. This situation has hindered rational policy making. Patent oppositions have been recognized as one effective way to contest abusive monopolies. Used since 2005 by NGOs from the Global South in their fight against HIV/aids, this legal procedure has allowed for public scrutiny of patents, raised awareness on the weakness of health inventions patents, and strengthened patentability analysis standards. Following this path, in July 2019, Médecins du Monde and Public Eye questioned a Car-t treatment tisagenlecleucel patent at the European Patent Office (EPO) based on its lack of inventive step.
Methods
We have filed a patent opposition to the patent EP3214091. A patent opposition is a legal procedure for challenging the validity of a granted patent based on lack of novelty, inventive step and/or industrial application. As a result, the patent may be maintained, amended or revoked. When revoked, the legal effects associated with the patent are suspended, including monopoly rights.
Results
In November 2019, in response to our patent opposition, Novartis and the University of Pennsylvania requested revocation of the patent. In December 2019, the EPO revoked patent EP3214091. Our patent opposition was effective to scrutinize patent EP3214091. This result weakened tisagenlecteucel monopoly and produced a strong argument for public officers to demand fairer prices. Other patents are in force that still do not allow the production of biosimilar versions of tisagenlecleucel.
Conclusions
We have showed a method through which monopoly abuses on new cancer treatments can be regulated. A stronger mobilization of oncologists is necessary to prevent abusive monopolies in order to safeguard sustainable access to cancer treatments.
Legal entity responsible for the study
The authors.
Funding
Médecins du Monde and Public Eye.
Disclosure
All authors have declared no conflicts of interest.
1590MO - Income loss after a cancer diagnosis from the patient perspective: An analysis based upon the German Socio-Economic Panel (SOEP) survey
- Diego Hernandez (Heidelberg, Germany)
Abstract
Background
Cancer treatments often require intensive use of healthcare services and limit patients’ ability to work, potentially causing them to become financially vulnerable. In Europe, research on this topic has been largely neglected, arguably due to the belief that financial hardship for cancer patients is not a major concern in European social welfare states. The present study is the first attempt to measure, on the German national level, the magnitude of income loss after a cancer diagnosis.
Methods
This study analyzes data from the German Socio-Economic Panel (SOEP) survey, one of the largest and most comprehensive household surveys in Germany, consisting of approximately 20,000 individuals, who are traced annually. The empirical strategy consists of OLS and multinomial logistic estimators to measure changes in job income, work status, working hours, and pension as a result of reporting a cancer diagnosis for the period between 2009 and 2015. Sample consistency checks were conducted to limit measurement error biases.
Results
Our empirical results show that job incomes dropped between 21% and 28% within the year a cancer diagnosis was reported. The effect persisted for two years after the diagnosis and was no longer observable in our data set after four years. The finding was linked to an increased likelihood of unemployment and a reduction of working hours by 24%. Pension levels, on the other hand, were not affected by a cancer diagnosis.
Conclusions
Our analysis suggests that many cancer patients are exposed to financial hardship in Germany, particularly when the cancer diagnosis occurs during their active life and before requirements to obtain a pension are met. Further research seems warranted to identify particularly vulnerable patient groups.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.