Early access routes to a European marketing authorisation
European legislation has tools that speed patients' access to medicines that address unmet medical needs. Accelerated assessment shortens the review of an application. A conditional marketing authorisation approves a medicine on less complete data and turns the evidence still missing into studies the company must carry out afterwards. An authorisation under exceptional circumstances gives access to a medicine whose comprehensive data cannot be obtained under normal conditions of use, under specific post-authorisation obligations. Adaptive pathways build a staged development of a medicine on these existing tools, conditional marketing authorisation in particular.
The early access tools
Accelerated assessment and conditional marketing authorisation are two key tools in European legislation for speeding patients' access to medicines that address unmet medical needs. Both are intended for innovative medicines that target a disease for which no treatment is available or that give patients a major therapeutic advantage over existing treatments. The European Medicines Agency's overview of the EU early access tools covers accelerated assessment, conditional marketing authorisation and compassionate use, all of them reserved for medicines addressing major public health needs. A medicine that fulfils the criteria of several early access tools and initiatives can use them in combination.
On 27 July 2015 the agency launched two-month public consultations, open until 30 September 2015, on revised guidelines for implementing accelerated assessment and conditional marketing authorisation. The revisions drew on the experience of implementing the two tools in recent years and on discussions of how to optimise their use at the European Commission's Expert Group on Safe and Timely Access to Medicines for Patients (STAMP). The agency expected the updated guidelines to optimise developers' use of the tools and so to allow more medicines that address unmet medical needs to reach patients earlier. By June 2016 the agency had published revised guidelines on implementing both tools.
Accelerated assessment
Accelerated assessment lets the agency's scientific committees assess an eligible medicine faster. A request for it rests on the medicine fulfilling major public health interest. The revision of the guideline proposed in 2015 included more detailed guidance on how to justify that interest. It proposed balancing the evaluation phases better, so that the agency's human medicines committee (CHMP) would reach its opinion within 150 days of the start of the procedure, against 210 days in a procedure that is not accelerated. It also emphasised early dialogue with the agency, so that accelerated assessment can be planned well ahead of submission.
Medicines assessed on an accelerated timetable
Maviret and Vosevi, two medicines for chronic hepatitis C virus infection in adults that the agency recommended for marketing authorisation in June 2017, were the first medicines for which accelerated assessment was carried out within 120 days. Hepatitis C virus infection was then a major public health challenge: it affected between 0.4% and 3.5% of the population in different member states, it was the most common single cause of liver transplantation in the EU, and about 15 million people in Europe were chronically infected. Because the infection is considered of major public health interest in terms of therapeutic innovation, both medicines were evaluated under the accelerated assessment mechanism, which aims to speed up patients' access to new medicines where there is an unmet medical need. The CHMP's opinions went to the European Commission for the adoption of decisions on EU-wide marketing authorisations through an accelerated procedure.
Oxlumo (lumasiran) was reviewed under the accelerated assessment procedure, which allows patients' access to medicines to be sped up. It was recommended on 16 October 2020 as the first treatment for primary hyperoxaluria type 1, a condition for which no medicine had been approved in the EU. Beyfortus (nirsevimab), recommended on 16 September 2022 to prevent respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants during their first RSV season, was evaluated under accelerated assessment because preventing RSV infection in all infants is considered of major public health interest. Abrysvo, a vaccine against RSV recommended in July 2023, was evaluated under the same mechanism because preventing RSV disease is considered of major public health interest. Emblaveo (aztreonam-avibactam), recommended in March 2024 for complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia and infections caused by aerobic Gram-negative bacteria where treatment options are limited, was evaluated under accelerated assessment because it is considered to be of major public health interest.
The CHMP reviewed the application for Evrysdi (risdiplam) under an accelerated timetable to enable faster patient access, and Evrysdi was recommended on 26 February 2021 as the first treatment that can be given orally to patients with certain types of spinal muscular atrophy. The CHMP did the same for Trodelvy (sacituzumab govitecan), recommended in October 2021 for adults with unresectable or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one of them for advanced disease. Chemotherapy was then the standard treatment for metastatic triple-negative breast cancer, but only an estimated 10 to 15% of patients responded to it and the time without their disease worsening was only 2 to 3 months, so there was a high unmet medical need for new treatments. Kimmtrak (tebentafusp), recommended in February 2022 for adults with uveal melanoma, a rare type of eye cancer, was also reviewed under an accelerated timetable, in view of the high unmet medical need.
Conditional marketing authorisation
Conditional marketing authorisation is one of the EU's regulatory mechanisms to facilitate early access to medicines for patients with an unmet medical need. It allows a medicine to be approved early on the basis of less complete clinical data than normally required. It is open to a medicine that addresses an unmet medical need and targets a seriously debilitating or life-threatening disease or a rare disease, or is intended for use in emergency situations in response to a public health threat. The available data, while less complete, must still demonstrate that the medicine's benefits outweigh its risks, and the applicant should be in a position to provide comprehensive clinical data after authorisation within a timeframe agreed with the CHMP. The benefit to public health of the medicine's immediate availability to patients must also outweigh the risk inherent in the fact that not all the data are yet available.
A conditional marketing authorisation is valid for one year. As part of the authorisation, the company is obliged to carry out further studies to obtain complete data, and the CHMP assesses the data these specific post-authorisation obligations generate at least annually to ensure that the balance of benefits and risks remains positive. At the end of its assessment the committee recommends renewing the conditional authorisation, not renewing it, or converting it into a standard marketing authorisation.
The revision of the guideline proposed in 2015 emphasised the importance for developers of planning a conditional marketing authorisation prospectively and of engaging in early dialogue with the agency and other stakeholders, for example through parallel scientific advice with health technology assessment bodies, which was expected to help translate conditional authorisations into early access for patients. It also updated the guidance on the extent and type of data required in annual renewal submissions.
In January 2017 the agency published a report on its experience with conditional marketing authorisation, based on the data collected over the ten years since 2006. In that period 30 medicines received a conditional authorisation, and none had to be revoked or suspended. They targeted seriously debilitating or life-threatening conditions such as HIV infection, breast cancer, severe epilepsy in infants and multi-drug-resistant tuberculosis, and 14 were orphan medicines, giving patients with rare diseases new therapeutic options. The report found that generating the additional data and converting a conditional authorisation into a full marketing authorisation took four years on average, and the agency took this to mean that patients with life-threatening or seriously debilitating conditions can access promising medicines earlier. The report identified possible areas for improvement:
- prospective planning of conditional authorisations and early dialogue with the agency to support the generation of high-quality data, timely discussion of additional post-authorisation studies and their feasibility, and better data generation for completing the specific obligations
- engaging the other stakeholders involved in bringing a medicine to patients, in particular health technology assessment bodies, so that all the data needed for decision-making are generated through one development programme
Medicines authorised conditionally
In February 2017 the agency recommended a conditional marketing authorisation for Natpar (parathyroid hormone), the first replacement therapy with parathyroid hormone for chronic hypoparathyroidism, a rare condition for which no treatment options were available, in patients who cannot be adequately controlled with standard treatment with calcium and vitamin D. In a trial of 124 participants randomised to Natpar or placebo in addition to standard treatment, 54.8% of those on Natpar reduced their calcium and vitamin D supplement doses by more than 50% while maintaining acceptable blood calcium, against 2.5% of those on placebo. As part of the conditional authorisation, the applicant was required to conduct a 26-week trial to study the medicine's safety and efficacy further, confirm the dosing schedule and assess the effects of treatment on symptoms and on quality of life, and the study was also to look at how calcium and phosphate are processed during treatment.
In December 2017 the CHMP recommended a conditional marketing authorisation for Crysvita (burosumab) for X-linked hypophosphataemia with radiographic evidence of bone disease in children from 1 year of age and adolescents with growing skeletons, a disease for which no medicine was authorised. The recommendation rested on two phase II studies, a main study in 53 children aged 5 to 12 and a second in 13 patients aged 1 to 4 whose response was similar, and on that basis the committee considered that the efficacy results in the older group could be extrapolated to the younger. As part of the conditional authorisation, the applicant was required to complete three ongoing studies to investigate the medicine's safety and efficacy further, with the data from all three planned for submission by 2020.
In March 2019 the agency recommended a conditional marketing authorisation for Waylivra (volanesorsen), the first medicine for familial chylomicronaemia syndrome, a rare disease for which no medicine was authorised and new treatments were urgently needed. The evidence was one phase III study in 66 patients, in which blood triglycerides fell on average by 77% after three months of treatment, against an increase of 18% on placebo. Because a number of cases of severe platelet reduction were seen in the trials, which may increase the risk of bleeding, additional risk minimisation measures were to be implemented, among them strict dosing guidance based on regular platelet monitoring and specific information for patients and their carers. As part of the conditional authorisation, the applicant was also required to conduct a study of the medicine's safety and efficacy and of the feasibility of those measures.
In July 2019 the CHMP recommended a conditional approval for Vitrakvi (larotrectinib) for adults and children with solid tumours that display a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, whose disease has spread or cannot be surgically removed and who have no other satisfactory treatment options. Its efficacy and safety were studied in three single-arm trials, with no control group, in a total of 102 evaluated adults and children who had already received standard therapy, would otherwise have had to undergo disfiguring surgery, or were unlikely to respond to available therapies. Of these, 67% responded, the response lasting six months or longer in 88% of responders and twelve months or longer in 75%, and tumour responses were seen both in rare tumour types such as infantile fibrosarcoma and salivary gland tumours and in common ones such as lung and colon cancer.
In October 2019 the CHMP recommended a conditional marketing authorisation for Ervebo, the first vaccine for active immunisation against Ebola virus disease of people aged 18 and over at risk of infection, a disease for which no therapy was approved. Data from clinical trials and compassionate-use programmes showed that Ervebo protects against the disease after a single dose. It had been tested in about 16,000 people in several clinical studies in Africa, Europe and the United States, where it proved safe, immunogenic and effective against the Zaire Ebola virus that circulated in West Africa in 2014–2016. In the 2019 outbreak in the Democratic Republic of the Congo it was used under an expanded access protocol, or compassionate use, to protect the people at highest risk of infection, such as healthcare workers, people who had come into contact with infected patients and contacts of those contacts, by a ring vaccination strategy, and preliminary data suggested that it was effective in that outbreak. Additional efficacy and safety data were being collected through the expanded access protocol and should be included in post-marketing safety reports, which the agency reviews continuously.
On 26 June 2020 the agency recommended a conditional marketing authorisation for Idefirix (imlifidase), the first treatment for adults waiting for a kidney transplant who are highly sensitised against the donor's tissue and have a positive crossmatch test against an available kidney from a deceased donor, a result that makes them ineligible for transplant. Idefirix should be used complementary to existing allocation programmes, for patients with a very low chance of finding a matching kidney despite those programmes. It was studied in three open-label, single-arm, six-month trials in which 46 sensitised patients were transplanted: all patients who were crossmatch positive at inclusion converted to negative within 24 hours of treatment, and the studies showed excellent results on kidney function and graft survival after six months. The company must submit additional efficacy and safety data from one observational follow-up study and one post-approval efficacy study.
In July 2020 the CHMP recommended a conditional marketing authorisation for Blenrep (belantamab mafodotin) for adults with relapsed and refractory multiple myeloma who no longer respond to an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody, patients who needed new treatments to improve survival beyond the three months or less then observed. The main study behind the recommendation was an open-label, randomised, two-arm phase 2 study of two doses in patients whose disease was still active after three or more lines of therapy. To characterise the medicine's effectiveness and safety better, the company has to submit the results of a randomised confirmatory phase 3 trial comparing Blenrep with pomalidomide plus low-dose dexamethasone, a standard treatment option for relapsed and refractory multiple myeloma, and the final results of the pivotal phase 2 study.
On 16 October 2020 the agency recommended a conditional marketing authorisation for Tecartus (autologous anti-CD19-transduced CD3+ cells) for adults with mantle cell lymphoma that has relapsed or is refractory after two or more lines of systemic therapy. In a multicentre trial, 74 patients received Tecartus, and 12-month follow-up showed an objective response rate, the proportion of patients with a certain reduction in tumour size, of 84%, and a complete response, the disappearance of signs of cancer, of 59%. The Committee for Advanced Therapies (CAT), the agency's expert committee for cell- and gene-based medicines, found that the benefits outweighed the possible risks for patients who had received more than two prior regimens including Bruton's tyrosine kinase inhibitors, and the CHMP agreed with that assessment and recommended conditional approval. Additional efficacy and safety data are being collected through long-term follow-up of the main study and through a registry-based study that will also collect data on long-term efficacy and safety in specific subgroups: the elderly, females and patients with severe disease.
In June 2021 the agency recommended a conditional marketing authorisation for Abecma (idecabtagene vicleucel) for adults with relapsed and refractory multiple myeloma who had received at least three previous therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and whose cancer had worsened since the last treatment. The main study was a phase 2, multicentre, open-label, single-arm trial in 140 such patients, of whom about 67% responded and maintained remission for about 11 months on average, and 30% responded completely. Additional efficacy and safety data are being collected through follow-up of the main trial and through an ongoing study comparing the medicine with standard triplet regimens.
In March 2022 the agency recommended a conditional marketing authorisation for Carvykti (ciltacabtagene autoleucel), a chimeric antigen receptor (CAR) T-cell medicine, for adults with relapsed and refractory multiple myeloma who had received at least three prior therapies and whose cancer had worsened since the last treatment. As an advanced therapy medicinal product it was assessed by the CAT, and the CHMP recommended approval on the basis of the CAT's assessment. The main study was a single-arm, open-label, multicentre trial in 113 patients who had received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, of whom about 84% responded durably and around 69% responded completely. Additional risk minimisation measures required of the marketing authorisation holder are to ensure that the centres dispensing the therapy are qualified to recognise and manage cytokine release syndrome and neurotoxicity. Further efficacy and safety data are being collected through follow-up of the main trial and through an ongoing study comparing the medicine with standard triplet regimens in relapsed and lenalidomide-refractory multiple myeloma.
The CHMP reviewed the application for Tecvayli (teclistamab) under an accelerated timetable to enable faster patient access, and the agency recommended a conditional marketing authorisation for it for adults with relapsed and refractory multiple myeloma who had received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and whose cancer had worsened since the last treatment. The recommendation rested on a phase 1/2, multicentre, open-label, single-arm trial in 165 patients, of whom 63% responded and lived without their disease getting worse for about 18 months on average. To characterise the medicine's safety and effectiveness better, the company has to submit data from a randomised phase 3 confirmatory study comparing teclistamab with subcutaneous daratumumab against daratumumab, pomalidomide and dexamethasone or daratumumab, bortezomib and dexamethasone, and the final results of the pivotal study.
On 13 October 2023 the CHMP recommended a conditional marketing authorisation for Elrexfio (elranatamab) as monotherapy for adults with relapsed and refractory multiple myeloma who had received at least three prior therapies and whose cancer had worsened since the last treatment. The pivotal part of an open-label, single-arm, multicentre phase 2 trial included 123 participants who had received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, but no prior therapy directed at B-cell maturation antigen: 61% responded, and more than 70% of those who responded have a probability of living without their disease getting worse for an average of 15 months. To confirm the results of the pivotal trial, the company has to submit data from a randomised phase 3 trial comparing elranatamab alone and with daratumumab against daratumumab, pomalidomide and dexamethasone in adults with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy, including lenalidomide and a proteasome inhibitor, and the final results of the pivotal phase 2 trial.
On 15 December 2023 the agency recommended Casgevy (exagamglogene autotemcel), a gene-editing therapy, for a conditional marketing authorisation. It is indicated for beta thalassaemia and severe sickle cell disease in patients aged 12 and over for whom haematopoietic stem cell transplantation is appropriate and no suitable donor is available. The recommendation was based on two ongoing single-arm trials in patients aged 12 to 35. Of 42 patients with transfusion-dependent beta thalassaemia in the primary efficacy set, including 13 adolescents, 39 were transfusion-free for at least one year. Of 29 patients with severe sickle cell disease, including six adolescents, 28 had no vaso-occlusive crises for at least 12 consecutive months. Safety was evaluated in the same two trials and a long-term follow-up study, in which 97 adolescents and adults were treated. The CAT found that the benefits outweighed the possible risks in patients with beta thalassaemia and sickle cell disease, and the CHMP agreed with that assessment and recommended approval. To confirm efficacy and safety, the company must submit the final results of the ongoing pivotal trials by August 2026, together with results from the long-term follow-up study and other studies of the product. Treated patients will be followed up for 15 years, and the company must also conduct a study based on data from a patient registry.
In May 2025 the agency recommended a conditional marketing authorisation for Aucatzyl (obecabtagene autoleucel), a genetically modified autologous CAR T-cell therapy, for adults from 26 years of age with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. The recommendation rested on the single-arm, open-label FELIX study in 113 patients, in which about 64% had a durable response, with a median duration of 14 months, and around 49% a complete response. The CAT found that its benefits outweighed the possible risks, and the CHMP agreed with that assessment. To confirm the medicine's safety and efficacy, the company was requested to submit long-term follow-up results of the FELIX study and to conduct a non-interventional study based on a patient registry.
In June 2025 the agency recommended a conditional marketing authorisation for Zemcelpro (dorocubicel/unexpanded umbilical cord cells) for adults with haematological malignancies who require an allogeneic haematopoietic stem cell transplantation following myeloablative conditioning and for whom no other type of suitable donor cells is available. The recommendation rested largely on a pooled analysis of two single-arm, open-label studies in 25 patients, of whom 21 (84%) achieved neutrophil engraftment within a median of 20 days and 17 (68%) platelet engraftment within a median of 40 days. The CAT found that its benefits outweighed the possible risks in patients with haematological malignancies requiring an allogeneic haematopoietic stem cell transplantation for whom no matched donor cells are available, and the CHMP agreed with that assessment. To confirm the medicine's safety and efficacy, the company was requested to submit long-term follow-up results of the single-arm studies and to conduct a randomised controlled study and a study based on a patient registry.
In January 2026 the agency recommended a conditional marketing authorisation for Rezurock (belumosudil) for chronic graft-versus-host disease in adults and in children aged 12 years and older weighing at least 40 kg, to be used when other treatment options provide limited clinical benefit, are not suitable or have been exhausted. The recommendation rested on an open-label study in patients whose condition was not sufficiently controlled with corticosteroids and at least two prior lines of systemic therapy, in which 73% responded over a six-month period, with 44% still showing a response at six months. To confirm the medicine's efficacy, the company committed to carrying out a confirmatory randomised controlled study.
A confirmatory study that failed
On 26 May 2023 the CHMP recommended revoking the marketing authorisation of Adakveo (crizanlizumab), granted in October 2020 to prevent painful vaso-occlusive crises in patients aged 16 years and older with sickle cell disease. At the time of authorisation the data showed that Adakveo reduced the number of painful crises, but they were limited and there was some uncertainty about the size of the effect, so the agency requested the STAND study as a condition of the authorisation. The STAND study did not confirm the benefit: patients on Adakveo had on average 2.5 painful crises with a subsequent healthcare visit over the first year of treatment, against 2.3 on placebo, and 4.7 crises requiring a healthcare visit or treatment at home, against 3.9. It raised no new safety concerns but showed a higher rate of severe and serious treatment-related side effects with Adakveo than with placebo. Data from other studies, a managed access programme and real-world data had limitations, such as the lack of a comparator, and could not show the effect of Adakveo or counterbalance the negative results of the STAND study, so the committee concluded that the benefits did not outweigh the risks. Its opinion went to the European Commission, which issues a final legally binding decision applicable in all member states.
Authorisation under exceptional circumstances
A marketing authorisation under exceptional circumstances allows patients access to a medicine for which comprehensive data cannot be obtained under normal conditions of use, because there are only very few patients with the disease, because collecting complete information on the medicine's efficacy and safety is not possible or would be unethical, or because there are gaps in the scientific knowledge. Such medicines are subject to specific post-authorisation obligations and monitoring.
The CHMP recommended an authorisation under exceptional circumstances for Qalsody (tofersen), for adults with amyotrophic lateral sclerosis (ALS) who have a mutation in the superoxide dismutase 1 (SOD1) gene. The committee based its opinion on the totality of evidence, including the targeted way the drug works, effects observed in a SOD1 animal model, biomarkers and clinical data. The clinical data came from a 28-week, randomised, double-blind, placebo-controlled study in which 108 patients were randomised 2:1 to intrathecal Qalsody or placebo for 24 weeks. Plasma neurofilament light chain, a marker of damage to axons, fell by approximately 60% against placebo, suggesting reduced neuronal injury, and the patients' physical abilities on the ALS Functional Rating Scale–Revised (ALSFRS-R) improved numerically. The CHMP requested post-authorisation data to characterise the medicine's long-term efficacy and safety further, from an open-label long-term extension study, collaboration with two disease registries and an observational registry-based study. Whether tofersen can delay or even prevent the emergence of clinically manifest ALS in presymptomatic patients with SOD1-ALS is also to be investigated.
On 14 October 2022 the agency recommended a marketing authorisation under exceptional circumstances for Ebvallo (tabelecleucel) for adults and children with Epstein-Barr-virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy and whose disease has come back after treatment or not responded to it. Patients whose first-line therapies fail have a significant unmet need, as they survive only weeks to a few months after the failure and other treatment options are limited. Tabelecleucel is an advanced therapy medicinal product. The recommendation was based on an ongoing multicentre, phase 3, single-arm, open-label trial in 43 patients. About half achieved partial or complete remission, and a significant number had a durable response of six months or more. The CAT found that the benefits outweighed the risks in patients with EBV+ PTLD, and the CHMP agreed with the CAT's assessment and positive opinion and recommended approval under exceptional circumstances. The CHMP asked the applicant for data further characterising long-term efficacy and safety in the trial patients, and for a post-authorisation observational safety study in patients treated in Europe, whose protocol must be submitted within three months of the marketing authorisation.
Adaptive pathways
Adaptive pathways are a planned, progressive approach to bringing a medicine to patients, not a new route of marketing authorisation, and they make use of existing regulatory tools. In particular they use conditional marketing authorisation, in operation in the EU since 2006, and they build on the experience gained with the strengthened post-marketing monitoring tools introduced by the 2012 pharmacovigilance legislation. Under the approach a medicine is first approved early for a small, restricted patient population likely to benefit most from it, on the basis of small initial clinical studies, and evidence gathered over time from its use and from additional studies leads to progressive adaptations of the marketing authorisation that expand access to broader populations or restrict its previously authorised indications. The approach is not meant for all medicines, but only for medicines likely to address an unmet medical need, and the development also needs to meet the characteristics of adaptive pathways.
A key aspect of adaptive pathways is the involvement of all relevant decision makers across a medicine's lifespan, including those who decide about patient access in the member states. The agency considers it particularly important that all the stakeholders involved agree on a plan of post-licensing knowledge generation before the medicine is authorised, and that the marketing authorisation holder commits to carrying out the plan. Once the authorisation is granted, the post-authorisation plan becomes a legally binding regulatory obligation. In 2016 the agency described adaptive pathways as still a developing concept, to be refined as more medicines are considered for the approach. Cooperation between stakeholders and a strong pharmacovigilance system are the basis for systematically monitoring the safety and overall performance of a medicine in clinical practice.
The case for adaptive pathways
A number of scientists, including members of the agency and its scientific committees, hold that adaptive pathways should be the preferred approach in the near future to bring new medicines to patients. The key drivers they identify include:
- patients' demand for timely access to medicines, in particular where medical needs are unmet; with adaptive licensing, new treatments would reach some patients earlier, on a smaller evidence base, if efficacy has been observed in that population
- a better understanding of pathologies, which has identified subgroups of patients likely to respond better to certain medicines than others, and for many of these subgroups a progressive approach to licensing while learning from real-world experience may become the only viable route to new treatments
- the growing financial pressure on healthcare systems, and a call for more targeted use of medicines to increase their therapeutic value
- the pressure on industry to make the development of medicines sustainable, in particular for chronic diseases; development programmes targeting smaller, better-defined populations would lower the threshold for financing a drug's development and allow more medicines to be brought forward
As of 2015, developments fostering the transition from a traditional approach, with large trials and a marketing authorisation for broad groups of patients, to an adaptive one included innovative clinical trial designs, learning healthcare systems and the inclusion of patients in decision-making to understand better what level of uncertainty they are willing to accept.
The agency's pilot
The agency launched a pilot project on adaptive pathways in March 2014 to explore the approach with medicines already in development. It renamed the project from adaptive licensing to adaptive pathways to reflect a life-span approach in which clinical development, licensing, reimbursement, use in clinical practice and monitoring are viewed as a continuum. It invited companies to submit ongoing development programmes with the characteristics of adaptive pathways: a staggered approval from very small, restricted patient populations to increasingly wider ones, a binding plan of post-licensing evidence gathering, and the involvement of key stakeholders in the process. By November 2014 the agency had received and assessed 29 applications, nine of which had been selected for discussion with the applicant. Stage I was to close at the end of February 2015, after which the agency would focus on stage II and its in-depth face-to-face meetings with the selected applicants, and would still consider well-developed new applications for those meetings. Applicants could contact the agency for advice on the content and suitability of a request to be considered for stage II. The agency planned to publish a report on initial experience with the pilot by the end of 2014.
On 3 August 2016 the agency published the final report on the pilot, which had ended. The agency reported that the pilot showed that adaptive pathways can bring regulators, health technology assessment bodies, healthcare professionals and patients together to agree on a prospective plan for generating data on a medicine across its lifespan in areas of unmet medical need. It also held that adaptive pathways can support medicine development in therapeutic areas where evidence generation is challenging, such as infectious diseases, Alzheimer's disease, degenerative diseases and rare cancers. The pilot also identified aspects for further reflection: increased involvement of patients in selecting candidates for adaptive pathways, methodologically sound strategies for collecting real-world evidence to support the assessment of both efficacy and effectiveness, and the potential involvement of payers, the member states' organisations responsible for decisions on pricing and reimbursement, to give input on pricing strategies.