Early Access Scheme Research Articles

Advancing early access policies for innovative cancer drugs: a scoping review and explorative analysis in the Italian setting.

Considering the clinical impact of innovative cancer therapies, policy makers strive to balance timely access and thorough value-assessment. While some European countries promoted early access schemes, Italy does not yet display a consolidated strategy for innovative drugs or for medicines targeting pathologies with a high unmet need. To better understand the risks and opportunities of early access strategies that could be applied in the Italian setting, we performed a scoping review, searching the PubMed and Web of Science databases and interviewing two field experts. The review results were complemented with an exemplificative quantitative analysis for a subset of innovative oncology drugs, to assess the clinical and economic impact of the price and reimbursement negotiation. Our study suggests that early access schemes developed in Germany and France, combining a free-pricing period, pay-back mechanism, and arbitration, could serve as a basis for developing a feasible strategy in Italy. The quantitative analysis indicated that timely access to innovative drugs could have potentially prevented many cancer progressions, associated with a significant healthcare expenditure. Albeit not allowing to express a conclusive assessment, this study proposes a potential early access strategy for Italy and highlights the need for opening a debate on the opportunities and risks of such schemes.

The economic impact of 14 compassionate use programs for medicines in Italy, in the perspective of the National Health Service

Background: Compassionate use programs (CUP) for medicines allow patients, not recruited in trials, accessing medicines before marketing approval. The evidence on the economic impact of CUP is limited to one paper that did not include the possible long-term economic impact of medicines used in CUP compared to alternative treatments, like avoided hospitalization costs. This paper aims at covering this information gap, updating and integrating the existing evidence, with a cost analysis in the perspective of the Italian National Health Service (SSN). Methods: Data were retrieved from the Roche CUP Database, the peer-reviewed literature (e.g. published cost-effectiveness studies, if any), the gray literature (e.g. regional documents for the alternative treatment cost) and unpublished data (e.g. cost-effectiveness analysis provided for price and reimbursement negotiation for medicines in CUP). Results: We retrieved data from 14 CUPs and 3,485 patients (70% affected by tumors) (Jan 2015-August 2022). The alternative treatment mean cost per patient ranged from € 11.1 k to € 18.8 k. The net economic benefit ranged from € 47 million to € 75 million (€ 13.5 k-€ 21.5 k per patient). Avoiding alternative treatments mostly contributes to the economic benefit. The long-term economic impact accounted for 20/30% of the net economic impact. The net economic benefit for cancer drugs ranged from € 12.6 million to € 40.0 million. Conclusions: Despite research limitations, this paper provides additional evidence on the economic impact of CUP in Italy. This could represent the first step of a broader analysis of the economic impact of early access schemes for drugs.

Unmet need: definitions, literature evidence and implications for HTA

The present paper illustrates the definition of unmet need provided by the peer-reviewed literature and the Health Technology Assessment (HTA) authorities across Europe in the assessment and appraisal process and within the early access schemes for medicines. The analysis relied on a descriptive review of the peer-reviewed literature and HTA documents on the definition of need (disease severity) and the way it is satisfied (existence and validity of alternatives). HTA agencies were found using (i) a narrow definition of need, focused on the clinical impact and the impact on health-related quality of life of the disease and (ii) a broad definition of comparators, including treatments used off-label in the clinical practice. Most of the contributions of the literature advocated for a broader definition of need, including additional dimensions (for example, the socio-economic impact of the disease) and the effects of existing treatments beyond their risk-benefit profile (for example, acceptability to patients). On the one hand, these contributions should be considered by HTA agencies, considering its multi-disciplinary and multi-stakeholder nature. On the other one, the explicit inclusion of the unmet need domains, at present disregarded, should depend on the decisions taken on the ground of the assessment.

A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program.

The Ibrance® Patient Program was established to provide access to palbociclib for UK National Health Service (NHS) patients with metastatic breast cancer (MBC), pending a funding decision. Non-interventional cohort study involving a retrospective medical record review of patients commenced on palbociclib between April and December 2017 at eight UK centres. Primary outcomes included clinicopathological characteristics, treatment patterns, clinical outcomes and selected adverse events. Overall, 191 patients were identified, median age of 57.0 years (range 24.3-90.9); 30% were diagnosed with de novo MBC; 72% received first-line and 10% as ≥ second-line treatment. Median progression-free survival (95% CI) was 22.8 months (16.5-not reached [NR]) in first-line; NR in patients with de novo MBC; 7.8 months (6.8-NR) in ≥ second-line (median follow-up: 24 months). Median overall survival (OS) was NR in the overall cohort; OS rate (95% CI) at 24 months was 74.2% (67.1-81.9%) in first-line; 82.1% (72.6-92.8%) in patients with de novo MBC; 55.0% (37.0-81.8%) in ≥ second-line. Forty-seven per cent of patients developed grade 3-4 neutropenia; 3% febrile neutropenia. This study supports the effectiveness of palbociclib and demonstrates the benefit to patients of early access schemes that bridge the gap between regulatory approval and NHS funding for new medicines. Clinical trial: ClinicalTrial.gov:NCT03921866.

5613294 BASELINE PATIENT CHARACTERISTICS FROM A UK EARLY ACCESS TO MEDICINES SCHEME (EAMS) WITH VOXELOTOR, A HBS POLYMERIZATION INHIBITOR, FOR THE TREATMENT OF HEMOLYTIC ANEMIA DUE TO SICKLE CELL DISEASE

Background: Standard of care for patients with sickle cell disease (SCD) typically includes blood transfusions and treatment with hydroxyurea (HU). Voxelotor, a first-in-class oral treatment, inhibits sickle hemoglobin polymerization, the molecular basis of red blood cell sickling. Voxelotor is approved in the United States for the treatment of SCD in patients aged ≥4 years and in the European Union, Great Britain, United Arab Emirates, Kuwait, and Oman for patients aged ≥12 years. Voxelotor has been provided to eligible patients with SCD in the United Kingdom (UK) through a Medicines and Healthcare Products Regulatory Agency – approved Early Access to Medicines Scheme (EAMS) and through a company Named Patient Program (NPP), both of which allow patients to receive new, unlicensed medicines when there is a clear unmet need. Aims: To describe the UK patient population participating in the voxelotor EAMS and NPP for the treatment of hemolytic anemia due to SCD. Methods: Patients aged ≥12 years with hemoglobin (Hb) ≤10.5 g/dL received voxelotor. The EAMS permitted patients to receive a stable dose of HU for 3 months prior to starting voxelotor, whereas NPP allowed patients who were ineligible or intolerant to HU, had a poor/no response to HU, or had stopped taking HU. Data on demographics, comorbidities, concomitant medications (including blood transfusions), adverse events, markers of hemolysis, vaso-occlusive crises (VOCs) requiring treatment and/or hospitalization, and discontinuation of therapy were collected. Results: As of August 22, 2022, 90 patients (61 in the EAMS and 29 in the NPP) were enrolled. Overall, the mean age (range) was 37.82 years (12-66), 53.33% (48/90) were female, 75.56% (68/90) were of African or Afro-Caribbean origin, and the most common genotype was HbSS (97.78%, 88/90) (Table). At baseline, mean (SD) [range] Hb was 7.54 (1.43) [4.6-10.8] g/dL. At baseline, 45.9% (28/61) of patients were taking HU, and 18.03% (11/61) had discontinued previous use of HU; 1.64% (1/61) had been treated with crizanlizumab, and 50.82% (31/61) reported having simple and/or exchange transfusions. In the 12 months before initiating voxelotor, the mean (SD) number of VOCs requiring hospitalization was 0.84 (1.52). Other reasons for hospitalization included admission for VOC (24.59%, 15/61), acute chest syndrome (4.92%, 3/61), transfusion (9.84%, 6/61), hyperhemolysis (3.28%, 2/61), and other (9.84%, 6/61). A total of 9.84% (6/61) of patients reported ≥3 emergency department (ED) admissions, and alloimmunization was reported in 19.67% (12/61) of patients. Summary/Conclusion: The UK EAMS and NPP provide voxelotor to patients with SCD with limited treatment options. Clinical measures, ED visits, and hospital admission rates of patients participating in the voxelotor EAMS and NPP demonstrate the characteristics of patients selected for the early access scheme and highlight the unmet treatment needs among representative patients with SCD in the UK. Baseline hemolytic parameters and Hb levels are critical not only for defining patient eligibility, but as follow-up measures for patients while receiving voxelotor treatment. Data on the impact of voxelotor on clinical outcomes are forthcoming. Funding: This study was supported by Global Blood Therapeutics.Reference 1. Medicines and Healthcare Products Regulatory Agency. Voxelotor: treatment protocol: information on the pharmacovigilance system. Updated August 5, 2022. Accessed August 28, 2022. https://www.gov.uk/government/publications/voxelotor-in-the-treatment-of-sickle-cell-disease/voxelotor-treatment-protocol-information-on-the-pharmacovigilance-system

Audit of Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma Treated in the Early Access Scheme

Purpose: Maintenance avelumab following first line platinum-based chemotherapy prolongs survival in advanced urothelial carcinoma. We audited the outcomes and tolerability of maintenance avelumab in patients who have been started on treatment in the EAMS setting.

Early access schemes for innovative health technologies: the views of international stakeholders.

Early access schemes (EASs) are approaches used by payers to balance and facilitate earlier patient access to innovative health technologies while evidence generation is ongoing. Schemes require investment from payers and are associated with significant risk since not all technologies will be routinely reimbursed. The purpose of this study was to gain the perspectives of policy experts about the key challenges for EASs and potential solutions for their optimal design and implementation. Two virtual workshops were convened including (i) UK-based policy experts (England, Wales, and Scotland) and (ii) representatives from multiple healthcare systems (England, France, Sweden, Canada, Poland, and Norway). Participants were encouraged to share their experiences with EASs in their healthcare system and highlight key challenges for policy makers. Discussions were transcribed and analyzed using framework analysis. Participants agreed that EASs have value when targeted toward innovative technologies with the potential for significant clinical benefit in an area of high unmet need. Participants discussed potential solutions to the challenges faced by payers implementing EASs, including defining eligibility criteria, supporting evidence generation, and approaches to reimbursement. Participants agreed that EASs are one possible solution for their healthcare systems and have the potential to deliver significant clinical value to patients. However, widespread adoption of EASs is limited due to concerns about the risks for patients and healthcare budgets, further solutions are needed to deliver EASs for targeted therapies.

Exploring alternative financing models and early access schemes for orphan drugs: a Belgian case study.

Although some jurisdictions have implemented particular adjustments to accommodate often-expensive orphan drugs in their healthcare systems, availability of these drugs remains complex. This study investigates alternative financing models and early access schemes for orphan drugs in the context of the Belgian healthcare system. Three focus group discussions were held with a panel of eleven experts from the Belgian Drug Reimbursement Committee, the Colleges for Orphan Drugs, the pharmaceutical industry, physicians, ethicists and pharmacists. Retrieved data were pseudonymised, analysed and coded according to the Qualitative Analysis Guide of Leuven. Experts disfavoured the insulated fund as well as private insurance for financing orphan drugs, as, respectively, isolation of a separate budget and a mostly profit-driven mechanism would contradict the Belgian fundamental principle of solidarity. Moreover, an insulated fund could, albeit on a smaller scale, reproduce the same budgetary constraints as the general reimbursement system. As the Special Solidarity Fund is intended for urgent care and exclusively accommodates financial needs subject to eligibility criteria, its design would not allow general financing of orphan drugs. Overall, implementation of an alternative financing model was not endorsed, instead, improving the current reimbursement system was preferred. Suggestions mentioned were; increased collaboration and transparency, robust and quality real-world evidence but also digitalization of data. Alleviating administrative burden and simplifying the admission process of compassionate use program, medical need program and early treatment reimbursement should be prioritized to facilitate early access. Furthermore, a legal framework for off-label use could stimulate proper implementation. Efforts on collaboration of expertise centres and coordination of orphan drug databases across Europe could foster a robust data network to support orphan drug availability in individual countries. This research reveals that reassessing current financing models and early access schemes by eliminating inadequacies, may be more conducive than establishing alternative systems to increase availability of orphan drugs in Belgium. Other jurisdictions may rely on this information to review their own models of early access and financing to cultivate a more sustainable delivery of orphan drugs.

HPR102 Exploring Alternative Financing Models and Early Access Schemes for Orphan Drugs: A Belgian Case Study

HPR102 Exploring Alternative Financing Models and Early Access Schemes for Orphan Drugs: A Belgian Case Study

HPR53 Changes to Early Access Scheme in France: Early Learnings for Orphan Drugs

HPR53 Changes to Early Access Scheme in France: Early Learnings for Orphan Drugs

The regulatory, evaluation, pricing and reimbursement pathway for medicines in the UK: combining innovation and access

The United Kingdom has universal healthcare systems, the National Health System (NHS), in its four nations, with healthcare services provided free of charge at the point of delivery. Approximately 10.5% of the UK population has voluntary supplementary private health insurance. While the provision of inpatient medicines is free of charge, medicines provided in the outpatient setting have a dispensing fee in some of the nations, such as the case of England (co-payment). The UK marketing authorisation process is called product licensing and is overseen by the Medicines and Healthcare Products Regulatory Agency (MHRA). There are different licensing routes based on the intended market for launch. MHRA also offers early access schemes and pathways for products targeting unmet medical needs and promising technologies, that aim to accelerate and facilitate market and patient access to products in the UK. These schemes include the option for companies to engage early with regulators and other system partners such as health technology assessment (HTA) agencies. As soon as the technology is authorised, it is available at a list price. Prices for medicines are regulated in legislation and in schemes agreed between the industry association and the Department of Health and Social Care (DHSC). The prices for the NHS are negotiated between the government and the companies. Routine funding decisions in the NHS are guided by HTA evaluations informed by agencies such as the National Institute for Health and Care Excellence (NICE) in England, the Scottish Medicines Consortium (SMC) in Scotland, and the All Wales Medicines Strategy Group (AWMSG) in Wales. Many medicines and other technologies are subject to price negotiations in the NHS, sometimes with confidential price agreements. The NHS in England is legally mandated to routinely fund technologies recommended by NICE that have been evaluated by some of its programmes. The other UK nations have similar arrangements or recognise decisions made in England. The role and contribution of NICE and other HTA agencies in ensuring value for money and evidence-based decision making is well recognised worldwide.

POSB279 A Comparison Study of Prices and Market Access Delays for ATUC Drugs in France Versus EU4 & UK

Autorisation Temporaire d’Utilisation de Cohorte (ATUc) is a French early access scheme dedicated to presumed innovative treatments before marketing authorization, and limited to patients with the highest need. These treatments are funded by the National Health Insurance at a price freely set by pharmaceutical companies. This research aims to compare ATUc prices versus launch prices in France, Germany, Italy, Spain and the United Kingdom, and to observe market access delays.

Clinical development of cell therapies for cancer: The regulators' perspective

Novel cell therapies for haematological malignancies and solid tumours address pressing clinical need while offering potentially paradigm shifts in efficacy. However, innovative development risks outflanking information on statutory frameworks, regulatory guidelines and their working application. Meeting this challenge, regulators offer wide-ranging expertise and experience in confidential scientific and regulatory advice. We advocate early incorporation of regulatory perspectives to support strategic development of clinical programmes. We examine critical issues and key advances in clinical oncology trials to highlight practical approaches to optimising the clinical development of cell therapies. We recommend early consideration of collaborative networks, early-access schemes, reducing bias in single-arm trials, adaptive trials, clinical end-points supporting risk/benefit and cost/benefit analyses, companion diagnostics, real-world data and common technical issues. This symbiotic approach between developers and regulators should reduce development risk, safely expedite marketing authorisation, and promote early, wider availability of potentially transformative cell therapies for cancer.

Early patient access to health technologies: Is innovation needed for early management?

The question of early patient access to innovative health technologies arises from the assumption that, once a certain level of effectiveness or efficiency is achieved, waiting for mainstream coverage would represent a loss of opportunity for patients or for the community. This was the premise on which the round table based its dialogue. Early access is understood as the funding of a technology that comes within this field and is CE-marked but has not yet attained "mainstream" coverage. There are several early access schemes in France ("forfait innovation", early coverage, exceptional coverage, RIHN). This round table was an opportunity to establish mapping, extended to devices not dedicated to early access but which could nevertheless provide some patients with access to non-mainstreamed technologies (Article 51, ETAPES experiments, DGOS call for projects, local schemes). It is an initial step that would need to be further developed and complemented by the dissemination of common communication materials available to all, including patients. The existing schemes are in fact still poorly known. Consideration would also have to be given to the advisability of developing these schemes in order to adapt them to the new European requirements. More generally, early access schemes must be integrated into an ecosystem that is conducive for their relevance: consideration of procedures associated with medical devices benefiting from early access; short time frames of examination; patient information. Finally, the round table proposes the creation of a new early access scheme, complementary to those that exist and that would be positioned, after CE marking, between the "forfait innovation" and mainstreaming: PRESTO (Prise En charge Sécurisée et Temporaire de technologies innOvantes) (secure and temporary coverage for innovative technologies).

PND134 HTA AND ACCESS FOR ORPHAN DRUGS: IDENTIFICATION OF 4 CRITICAL DIFFERENCES BETWEEN UK AND US PATHWAYS

Exponentially increasing orphan drug prices has negatively impacted reimbursement decisions, limiting patient access. Availability of orphan drugs varies jurisdictionally, as do the HTA and access processes. To compare the UK and US, four mutual themes will be identified to highlight the differences in orphan drug processes and the associated effects. A systematic literature review was conducted on publications, indexed in PubMed and EMBASE, to identify, via scoring and ranking, comparative and contrasting themes between the UK and US. Articles published after 10/06/2016 were selected using inclusion and exclusion criteria and were confirmed for validity using CASP checklists. Findings were tested and confirmed through interviews, following predefined discussion guides with experts in orphan drug HTAs and market access. Four themes emerged from the literature review, which were used to compare the UK and US: HTA pricing, reimbursement and funding, time-to-market, and patient access and prescribing. Free-pricing between US healthcare providers resulted in varying prices for the same drug, whereas the UK-based NICE HTA outcomes achieved fixed-pricing for all patients. Likewise, due to the US competitive pricing environment, orphan drugs were priced considerably higher than in the UK. Both countries offered public funding opportunities, aiding treatment financing and access. However, considerably more orphan drugs received reimbursement in the US than the UK. Both countries offered early access, or fast-track approval, in cases tackling significant unmet need. Analysis using the four criteria identified that orphan drug prices in the US were considerably higher than the UK. Both countries offered accelerated or early access schemes and public funding, yet patient access was challenged due to reimbursement and funding limitations. Although market access is higher in the US, varying healthcare plan portfolios, and price variability, limits patient access. The UK reimburses fewer orphan drugs, but all UK patients have access to reimbursed treatments.

Early Access Schemes and Pricing Strategies: A Case Study on Temporary Authorization for Use in France from 1994 to 2016

Les procédures d’accès précoce à l’innovation rendent possible l’accès aux médicaments qui n’ont pas encore obtenu leur autorisation de mise sur le marché (AMM) à une population prédéfinie de patients. Dans le cadre réglementaire français, sous ce régime appelé « Autorisation Temporaire d’Utilisation » (ATU), les prix ne sont pas réglementés : ils sont librement fixés par le laboratoire pharmaceutique, ce qui contraste avec le système des prix administrés en vigueur pour les médicaments remboursés. Cette étude contribue à la littérature peu abondante sur le sujet en analysant le régime d’ATU depuis sa mise en œuvre en 1994 jusqu’en 2016. Cette longue période permet de documenter et de décrire le régime des ATU et son impact sur les prix. Nous analysons la différence de prix entre le prix librement établi sous ATU et le prix post AMM, après négociation avec le Comité Économique des Produits de Santé (CEPS). Notre principal résultat montre qu’après la réforme réglementaire de 2007 qui a contraint, le cas échéant, les laboratoires pharmaceutiques à rembourser la différence entre le prix ATU et le prix post AMM, les prix post AMM négociés par le CEPS sont plus souvent inférieurs aux prix ATU. Plusieurs interprétations, non exclusives les unes des autres, peuvent être avancées pour expliquer ce résultat. Celui-ci peut signifier que la réforme a renforcé le pouvoir de négociation du CEPS. Il peut aussi signifier que le remboursement du trop-perçu pendant la période d’ATU ne constitue pas une incitation suffisante pour que les laboratoires modèrent véritablement leurs prix ATU. Enfin, il se peut qu’indépendamment de la réforme, les laboratoires surestiment depuis quelques années la valeur thérapeutique de leurs médicaments.

OP173 Eligibility Criteria For “Accelerated Access” Approval: A Global Survey

Introduction:Several early access schemes (EAS) exist, which aim to accelerate patient access to new, potentially life-saving therapies. While some information exists on key schemes and their modalities, the determinants that drive adoption of a new medicine under an EAS remain unclear. We aimed to map eligibility criteria for inclusion of new medicines into the different EAS available across countries.Methods:Health technology assessment (HTA) stakeholders across 23 countries globally were invited via email to complete a web-survey with questions on (i) items that define product eligibility for EAS designation, (ii) standards for minimum level of evidence, monitoring, and additional evidence generation for early access products, and (iii) funding arrangements for these products across settings and types of schemes. Anonymized responses were analysed using descriptive statistics.Results:Fourteen responses from 10 countries (including Belgium, England, France, Japan and Mexico, among others) demonstrated that “unmet clinical need” was paramount for EAS designation across all countries and types of schemes. The next most important factors were “phase-III trials underway” and “serious condition” for Compassionate Use Programme (CUP) and Named Patient Programme (NPP) inclusion (21 percent and 20 percent of respondents, respectively). “Measures in place to monitor risk” was key for CUP and NPP designation (43 percent and 27 percent of respondents, respectively), followed by “innovative product designation” for CUP and “scientific opinion” for NPP eligibility (14 percent and 23 percent of respondents, respectively). “No specific monitoring requirements” exist in Germany and Austria, whereas “reporting of adverse events” is crucial in France, England, Japan and Spain. NPP eligible products are mainly funded at a negotiated price and CUP designated products are largely provided by manufacturers free-of-charge (i.e. England, Scotland, Germany).Conclusions:Eligibility criteria/requirements and funding arrangements for early access vary considerably across settings and their respective EAS. Information from a larger sample of countries is required for an all-encompassing mapping of the early access products’ characteristics.

Empower: access to medicine - working towards early access.

Empower: Access to Medicine's contribution will document the founding of Empower: Access to Medicine and tactics used to create a lobbying campaign designed to facilitate the debate around barriers to medical innovation and patient access to medicines. The article will detail the evolution of the campaign's goals and the potential solutions to an expensive and slow system. Specifically the submission will look at the influence that Empower: Access to Medicine had on the Government's thinking and development of an early access scheme.

New Japanese Initiatives on Stem Cell Therapies

Two laws aiming to provide a new legal framework to promote regenerative medicine, while ensuring the efficacy and safety of the treatments, came into effect in Japan on November 25, 2014. The scope of these laws is briefly described here.

Nivolumab granted positive scientific opinion under UK early access scheme

Nivolumab granted positive scientific opinion under UK early access scheme