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European Regulators and Payers Initiatives for Drug Access: Collaborations or Divergences?
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VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
made in the healthcare system that result from the use of repurposed generic medicines. The proof of concept involved the development of health economic models for congenital hyperinsulinism, Wolfram syndrome, and Friedreich’s ataxia. These estimate the current cost to the NHS of treating each rare disease, and the potential savings that could be delivered to the NHS by successfully repurposing a generic drug to treat that disease. Using these models, a financial framework for a social impact bond was developed in collaboration with the NHS. Savings made by the NHS are paid into the bond when certain clinical landmarks are reached by patients being treated with newly repurposed drugs. This study has demonstrated that generic drug repurposing has the potential to save the healthcare system quantities of money sufficient to repay investment in a clinical trial, and build an investable and sustainable financial proposition. Crucially this model would deliver much needed new treatments to rare disease patients, treatments which would otherwise be considered financially inviable. PHP374 Strategic Considerations to Engage in Early Advice with European Health Technology Assessment Bodies Rémuzat C1, Kornfeld A1, Thivolet M1, Toumi M2 de Médecine, Laboratoire de Santé Publique, AixMarseille Université, Université de la Méditerranée, Marseille, France 1Creativ-Ceutical, Paris, France, 2Faculté
Background: Several health technology assessment (HTA) initiatives have been put in place in Europe: multi-HTA early advice (EUnetHTA), parallel scientific advice between European Medicines Agency (EMA) and HTA bodies, early dialogues between HTA bodies and EMA during adaptive pathways and priority medicines scheme and single national HTA early advice. Early HTA dialogues allow manufacturers to secure that their drug development plan addresses HTA agencies’ expectation but is not free of risk while benefits look obvious. Discussion: Before engaging in HTA early advice, pharmaceutical companies need to be well prepared to mitigate risk and get the most out of HTA bodies/EMA interactions. First, companies have to identify products for which to seek an advice and define portfolio priorities as process is time consuming. Then, companies have to identify appropriate timing to seek early HTA advice, i.e., very early in drug development or later. End of phase I might be too early while little information is available; HTA bodies might propose either unfocused or too much focused positioning. End of phase IIa might allow obtaining a better feedback when companies have actual questions on population/ indication; on the other side HTA bodies could widely impact drug positioning and request substantial changes in drug development plan, while it will be more difficult at end of phase IIb, as phase III needs to be replicated in the phase II population to obtain license. Finally, advice category to be selected depends on expected alignments and potential influence between HTA agencies/ EMA which might complicate development plan. Single HTA advice may prove useful when manufacturer want to address country specific issues but may increase HTA bodies’ divergence in their requirements. Conclusion: Engaging in early dialogues with HTA bodies is product and company specific and requires careful benefit-risk assessment; this requires following standardised process to ensure enlightened decision. PHP375 European Regulators and Payers Initiatives for Drug Access: Collaborations or Divergences? Rémuzat C1, Kornfeld A1, Falissard B2, Toumi M3 1Creativ-Ceutical, Paris, France, 2INSERM Unit U669 (Public Health and Mental Health), University Paris-Sud, Maison de Solenn, Paris, France, 3Faculté de Médecine, Laboratoire de Santé Publique, Aix-Marseille Université, Marseille, France
Background: Since High Level Pharmaceutical Forum, several initiatives have been put in place in Europe to promote early dialogue between stakeholders on relative effectiveness assessments. In 2010, European Medicines Agency (EMA) initiated collaboration with health technology assessment (HTA) bodies through parallel scientific advice procedure and recently, EMA engaged directly HTA bodies in early access pathways to innovative medicines (adaptive pathways (AP) and Priority Medicines Scheme (PRIME)) for early dialogues during the procedures. Despite these initiatives, gap between frameworks for repurposed products and for accelerated approval is widening between regulators and payers. Discussion: Regulators introduced several procedures related to drug repurposing, such as additional exclusivity periods for well-established substances having new therapeutic indication, developed for pediatric populations or granted an orphan drug designation. Issue of value recognition for repurposed products is currently on agenda of the European Commission. On the other side, repurposed products are stigmatized by payers because of low investment risk and perceived lack of innovation, and in some countries, already existing active substances are not eligible for HTA, and subject to systematic reference pricing. Since 2005, European regulators implemented five pathways to enhance early access of innovative medicines: marketing authorization under exceptional circumstances, conditional marketing authorization, procedure for accelerated assessment, AP and PRIME; however, these medicines are facing payers’ requirements for mature data before being able to achieve expected premium prices associated to their potential added value. Conclusion: Despite multiple initiatives and efforts, gaps between regulators and payers continue to widen, impacting patient access to new/repurposed medicines: lack of payers’ rewards for repurposed medicines creates disincentives for further development; payers’ aversion to uncertainty surrounding early drug access and lack of flexible pricing to raise price when new evidence is available, lead to delayed drug launch by manufacturers to generate more mature evidence and negotiate better prices. PHP376 Could European Regulators Contribute to Drug Budget Containment? Rémuzat C1, Thivolet M1, Falissard B2, Toumi M3
1Creativ-Ceutical, Paris, France, 2INSERM Unit U669 (Public Health and Mental Health), University Paris-Sud, Maison de Solenn, Paris, France, 3Faculté de Médecine, Laboratoire de Santé Publique, Aix-Marseille Université, Marseille, France
Background: European regulators recently suggested several measures to contribute to drug budget containment: 1) Fast-track approval for generics and biosimilars; 2) Supporting the development and approval of me-too medicines to stimulate availability of additional treatment options and competition; 3) Enhancing collaboration with health technology assessment (HTA) bodies during drug development to get value evidence generation satisfying both regulators and payers and facilitate collection of post-authorization evidence; 4) Lowering development costs through new licensing approach such as adaptive pathways. This research aims to analyse potential impact of these propositions on drug budget for health insurance. Discussion: It seems obvious that faster entry of generics and biosimilars will have positive impact on drug budget; however today, generic entry is fast and there is almost no room to speed it up, while for biosimilars the issue is more related to the adoption rate. Me-too products could contribute to lower budget if they target expensive products and can stimulate competition; however, when pharmaceutical companies decide not to invest in such products, this is generally more due to pricing and reimbursement issues, rather than regulatory hurdles. Increasing collaboration with regulators and payers allow to better address both side’s needs; however payers remains resistant to uncertainty displayed through accelerated pathways which might lead to deny added value and minimize price premium or even prevent drug reimbursement. Finally, drug price has never been driven by a cost-plus process but by value-based pricing, making irrelevant to improve development efficiency to lower pharmaceutical prices. Conclusion: Regulators’ impact on pharmaceutical prices is very limited with current policies. If regulators are entitled to request additional evidence for payers to be filed in the approval dossier, they may contribute to drug cost-containment mainly by delaying approval more than reducing prices. Approval of products with immature data remains an important payers’ issue. PHP377 Comparative Analysis of The Guidelines for Conducting Hta in Poland and Bulgaria Benisheva T, Trendafilova PD, Sidjimova DA, Vodenitcharov TV Medical University-Sofia, Sofia, Bulgaria
Objectives: The global economic recession is leading to reducing public health costs (including pharmaceutical expenditures) and development of HTA approach in the EC countries. As countries are striving to deliver universal health coverage, the process of deciding which health technologies and interventions have become increasingly important has been continuously evolving. Countries of EC are facing complex choices in deciding how to direct their health budgets to meet the priority health needs of their population, and how to sellect from the vast array of technologies and interventions on offer. Methods: Documentary method - Health technology assessment legislation and guidelines in Poland and in Bulgaria have been reviewed Method of critical analysis - Based on indicators the reviewed pulished documents are compared and analysed. Results: A comparative indicators analysis for conducting Health Technology Assessment (HTA) Guideline from April 2009 (Version 2.1), and the Regulation of the MoH of 2 April 2012 on the minimum requirements at the HTA in Poland and the Ordinance № 9 from December 2015 about the terms and conditions for HTA , including HTA Guideline in Bulgaria, have been assessed. Conclusions: The HTA approach in Poland is directed not only to the medicines but to the medical devices and special purpose dietary supplement as well, while in Bulgaria the HTA process is legally binding for the medicinal products only. Many HTA steps in Poland could be learned and applied in HTA process Bulgaria.
PHP378 Getting Medical Innovation to Patients in Developing Countries - A Systemic Approach to Setting Price and Access Shankar R IMS Consulting Group, Cambridge, UK
Biopharmaceutical companies are launching ever more medical innovations including lifesaving treatments for cancer and Hepatitis C. Fewer than 5% of patients who can benefit from medical innovation get access to this innovation within 5 years of launch in developing countries, even though these countries are increasingly moving toward universal coverage. One major reason for this is the inability of health systems and manufacturers to come to a common agreement on how to value innovative medicines and set price and access. Payers use tools such as therapeutic reference pricing, international reference pricing and cost effectiveness analysis in an ad hoc, non-transparent and unpredictable manner, which leads to delayed or limited or no effective access to innovative medicines. What is needed is a systemic approach to valuing medicines and setting price and access that enables health systems to deploy finite resources to address competing objectives of access, equity, quality, supply security, rational use and sustaining innovation. In this paper, based on an analysis of pricing and patient access (PPA) systems in both developed and developing countries, we develop a model PPA system that with some adaptations can work in most developing countries. Such a system allows payers to 1) discriminate between medicines based on the incremental value they offer over alternatives, 2) determine which pricing tools to use to set price and access based on above discrimination, and 3) devise innovative access arrangements to address clinical and financial uncertainties. This system aims to be fair, transparent in process and predictable in PPA outcomes. It also allows health systems to successfully negotiate prices and achieve patient access based on properly informed assessments. The paper also lays down the capabilities and institutional structures needed by health systems to deploy such a systemic PPA approach.
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
made in the healthcare system that result from the use of repurposed generic medicines. The proof of concept involved the development of health economic models for congenital hyperinsulinism, Wolfram syndrome, and Friedreich’s ataxia. These estimate the current cost to the NHS of treating each rare disease, and the potential savings that could be delivered to the NHS by successfully repurposing a generic drug to treat that disease. Using these models, a financial framework for a social impact bond was developed in collaboration with the NHS. Savings made by the NHS are paid into the bond when certain clinical landmarks are reached by patients being treated with newly repurposed drugs. This study has demonstrated that generic drug repurposing has the potential to save the healthcare system quantities of money sufficient to repay investment in a clinical trial, and build an investable and sustainable financial proposition. Crucially this model would deliver much needed new treatments to rare disease patients, treatments which would otherwise be considered financially inviable. PHP374 Strategic Considerations to Engage in Early Advice with European Health Technology Assessment Bodies Rémuzat C1, Kornfeld A1, Thivolet M1, Toumi M2 de Médecine, Laboratoire de Santé Publique, AixMarseille Université, Université de la Méditerranée, Marseille, France 1Creativ-Ceutical, Paris, France, 2Faculté
Background: Several health technology assessment (HTA) initiatives have been put in place in Europe: multi-HTA early advice (EUnetHTA), parallel scientific advice between European Medicines Agency (EMA) and HTA bodies, early dialogues between HTA bodies and EMA during adaptive pathways and priority medicines scheme and single national HTA early advice. Early HTA dialogues allow manufacturers to secure that their drug development plan addresses HTA agencies’ expectation but is not free of risk while benefits look obvious. Discussion: Before engaging in HTA early advice, pharmaceutical companies need to be well prepared to mitigate risk and get the most out of HTA bodies/EMA interactions. First, companies have to identify products for which to seek an advice and define portfolio priorities as process is time consuming. Then, companies have to identify appropriate timing to seek early HTA advice, i.e., very early in drug development or later. End of phase I might be too early while little information is available; HTA bodies might propose either unfocused or too much focused positioning. End of phase IIa might allow obtaining a better feedback when companies have actual questions on population/ indication; on the other side HTA bodies could widely impact drug positioning and request substantial changes in drug development plan, while it will be more difficult at end of phase IIb, as phase III needs to be replicated in the phase II population to obtain license. Finally, advice category to be selected depends on expected alignments and potential influence between HTA agencies/ EMA which might complicate development plan. Single HTA advice may prove useful when manufacturer want to address country specific issues but may increase HTA bodies’ divergence in their requirements. Conclusion: Engaging in early dialogues with HTA bodies is product and company specific and requires careful benefit-risk assessment; this requires following standardised process to ensure enlightened decision. PHP375 European Regulators and Payers Initiatives for Drug Access: Collaborations or Divergences? Rémuzat C1, Kornfeld A1, Falissard B2, Toumi M3 1Creativ-Ceutical, Paris, France, 2INSERM Unit U669 (Public Health and Mental Health), University Paris-Sud, Maison de Solenn, Paris, France, 3Faculté de Médecine, Laboratoire de Santé Publique, Aix-Marseille Université, Marseille, France
Background: Since High Level Pharmaceutical Forum, several initiatives have been put in place in Europe to promote early dialogue between stakeholders on relative effectiveness assessments. In 2010, European Medicines Agency (EMA) initiated collaboration with health technology assessment (HTA) bodies through parallel scientific advice procedure and recently, EMA engaged directly HTA bodies in early access pathways to innovative medicines (adaptive pathways (AP) and Priority Medicines Scheme (PRIME)) for early dialogues during the procedures. Despite these initiatives, gap between frameworks for repurposed products and for accelerated approval is widening between regulators and payers. Discussion: Regulators introduced several procedures related to drug repurposing, such as additional exclusivity periods for well-established substances having new therapeutic indication, developed for pediatric populations or granted an orphan drug designation. Issue of value recognition for repurposed products is currently on agenda of the European Commission. On the other side, repurposed products are stigmatized by payers because of low investment risk and perceived lack of innovation, and in some countries, already existing active substances are not eligible for HTA, and subject to systematic reference pricing. Since 2005, European regulators implemented five pathways to enhance early access of innovative medicines: marketing authorization under exceptional circumstances, conditional marketing authorization, procedure for accelerated assessment, AP and PRIME; however, these medicines are facing payers’ requirements for mature data before being able to achieve expected premium prices associated to their potential added value. Conclusion: Despite multiple initiatives and efforts, gaps between regulators and payers continue to widen, impacting patient access to new/repurposed medicines: lack of payers’ rewards for repurposed medicines creates disincentives for further development; payers’ aversion to uncertainty surrounding early drug access and lack of flexible pricing to raise price when new evidence is available, lead to delayed drug launch by manufacturers to generate more mature evidence and negotiate better prices. PHP376 Could European Regulators Contribute to Drug Budget Containment? Rémuzat C1, Thivolet M1, Falissard B2, Toumi M3
1Creativ-Ceutical, Paris, France, 2INSERM Unit U669 (Public Health and Mental Health), University Paris-Sud, Maison de Solenn, Paris, France, 3Faculté de Médecine, Laboratoire de Santé Publique, Aix-Marseille Université, Marseille, France
Background: European regulators recently suggested several measures to contribute to drug budget containment: 1) Fast-track approval for generics and biosimilars; 2) Supporting the development and approval of me-too medicines to stimulate availability of additional treatment options and competition; 3) Enhancing collaboration with health technology assessment (HTA) bodies during drug development to get value evidence generation satisfying both regulators and payers and facilitate collection of post-authorization evidence; 4) Lowering development costs through new licensing approach such as adaptive pathways. This research aims to analyse potential impact of these propositions on drug budget for health insurance. Discussion: It seems obvious that faster entry of generics and biosimilars will have positive impact on drug budget; however today, generic entry is fast and there is almost no room to speed it up, while for biosimilars the issue is more related to the adoption rate. Me-too products could contribute to lower budget if they target expensive products and can stimulate competition; however, when pharmaceutical companies decide not to invest in such products, this is generally more due to pricing and reimbursement issues, rather than regulatory hurdles. Increasing collaboration with regulators and payers allow to better address both side’s needs; however payers remains resistant to uncertainty displayed through accelerated pathways which might lead to deny added value and minimize price premium or even prevent drug reimbursement. Finally, drug price has never been driven by a cost-plus process but by value-based pricing, making irrelevant to improve development efficiency to lower pharmaceutical prices. Conclusion: Regulators’ impact on pharmaceutical prices is very limited with current policies. If regulators are entitled to request additional evidence for payers to be filed in the approval dossier, they may contribute to drug cost-containment mainly by delaying approval more than reducing prices. Approval of products with immature data remains an important payers’ issue. PHP377 Comparative Analysis of The Guidelines for Conducting Hta in Poland and Bulgaria Benisheva T, Trendafilova PD, Sidjimova DA, Vodenitcharov TV Medical University-Sofia, Sofia, Bulgaria
Objectives: The global economic recession is leading to reducing public health costs (including pharmaceutical expenditures) and development of HTA approach in the EC countries. As countries are striving to deliver universal health coverage, the process of deciding which health technologies and interventions have become increasingly important has been continuously evolving. Countries of EC are facing complex choices in deciding how to direct their health budgets to meet the priority health needs of their population, and how to sellect from the vast array of technologies and interventions on offer. Methods: Documentary method - Health technology assessment legislation and guidelines in Poland and in Bulgaria have been reviewed Method of critical analysis - Based on indicators the reviewed pulished documents are compared and analysed. Results: A comparative indicators analysis for conducting Health Technology Assessment (HTA) Guideline from April 2009 (Version 2.1), and the Regulation of the MoH of 2 April 2012 on the minimum requirements at the HTA in Poland and the Ordinance № 9 from December 2015 about the terms and conditions for HTA , including HTA Guideline in Bulgaria, have been assessed. Conclusions: The HTA approach in Poland is directed not only to the medicines but to the medical devices and special purpose dietary supplement as well, while in Bulgaria the HTA process is legally binding for the medicinal products only. Many HTA steps in Poland could be learned and applied in HTA process Bulgaria.
PHP378 Getting Medical Innovation to Patients in Developing Countries - A Systemic Approach to Setting Price and Access Shankar R IMS Consulting Group, Cambridge, UK
Biopharmaceutical companies are launching ever more medical innovations including lifesaving treatments for cancer and Hepatitis C. Fewer than 5% of patients who can benefit from medical innovation get access to this innovation within 5 years of launch in developing countries, even though these countries are increasingly moving toward universal coverage. One major reason for this is the inability of health systems and manufacturers to come to a common agreement on how to value innovative medicines and set price and access. Payers use tools such as therapeutic reference pricing, international reference pricing and cost effectiveness analysis in an ad hoc, non-transparent and unpredictable manner, which leads to delayed or limited or no effective access to innovative medicines. What is needed is a systemic approach to valuing medicines and setting price and access that enables health systems to deploy finite resources to address competing objectives of access, equity, quality, supply security, rational use and sustaining innovation. In this paper, based on an analysis of pricing and patient access (PPA) systems in both developed and developing countries, we develop a model PPA system that with some adaptations can work in most developing countries. Such a system allows payers to 1) discriminate between medicines based on the incremental value they offer over alternatives, 2) determine which pricing tools to use to set price and access based on above discrimination, and 3) devise innovative access arrangements to address clinical and financial uncertainties. This system aims to be fair, transparent in process and predictable in PPA outcomes. It also allows health systems to successfully negotiate prices and achieve patient access based on properly informed assessments. The paper also lays down the capabilities and institutional structures needed by health systems to deploy such a systemic PPA approach.