Overall survival: A trusted benchmark, but not always best

The preferred clinical endpoint in oncology clinical trials, OS serves as a trusted benchmark, offering wide ranging advantages over other endpoints^[1][2]. Defined as the time from randomization to death, OS is precise, objective, and relatively easy to measure. Given its clinical robustness and patient relevance, OS is universally accepted by regulators and health technology assessment (HTA) bodies alike^[2][3].

However, in some disease settings, OS is associated with important limitations^[2]. The need for long studies makes OS an unsuitable endpoint in the case of slowly progressing and early-stage cancers, for example. Measurement of OS is also susceptible to confounding, particularly when involving multiple lines of therapies, patient crossover, and the occurrence of non-cancer related deaths. Furthermore, OS does not capture the broader priorities of patients and physicians; for example, when quality of life is a priority over prolonging survival^[2]. For pharmaceutical companies, these limitations can translate into time and financial constraints.

Alternative oncology-relevant endpoints provide opportunities to address these concerns, allowing the collection of data at earlier time points than with OS (Figure 1)^[1]. Such endpoints allow measurement of outcomes before starting subsequent therapies, giving a more direct measure of treatment efficacy. Some endpoints also offer broader value to patients too – besides being surrogate endpoints for OS, non-OS endpoints can provide standalone information, including on symptoms, function, treatment burden, and quality of life^[4].

Figure 1: Alternative oncology-relevant endpoints

Source: Modified from Delgado and Guddati 2021^[1]
Abbreviations: EQ-5D, EuroQol 5-dimensions index; NSCLC-SAQ, Non-Small Cell Lung Cancer Symptom Assessment Questionnaire; PROs, patient reported outcomes.

Why aren’t alternative oncology-relevant endpoints used more widely?

Despite their potential value, alternative oncology-relevant endpoints remain underused in clinical trial design. In 2021, non-OS endpoints accounted for just 16% of primary endpoints in Phase II or Phase III oncology trials, with the most common being pathological complete response, relapse rate and disease-free survival^[5].

Major barriers to the broader adoption of alternative oncology-relevant endpoints in clinical trials include a lack of agreement on their value and the uncertainty among payers that they accurately capture treatment benefits for patients and healthcare systems^[4][6]. While regulators are generally more receptive towards non-OS endpoints, accepting measures that are reasonably likely to predict clinical benefit, HTA bodies typically require validation of surrogacy^[4][6]. In general, guidelines published by HTA bodies indicate a preference for OS data or consider surrogate endpoints only where validation studies demonstrate strong correlation with survival^[6]. From a payer perspective, this caution is arguably expected; several therapies approved on the basis of improvements in outcomes such as progression-free survival (PFS) have not demonstrated OS benefits^[2]. Despite this, few agencies provide detailed methodological guidance for surrogacy validation^[7].

This uncertainty is further confounded by differences in the willingness of national HTA bodies to evaluate even well-established alternative oncology-relevant endpoints such as PFS^[6]. The resulting complexity feeds a vicious cycle: a lack of standardized methodologies for evidence generation leads to insufficient evidence to quantify the long-term benefits of non-OS endpoints, deterring HTA bodies from giving due consideration to these outcomes in decision making^[6].

Moreover, while HTA bodies continue to place particular importance on mortality, patients and clinicians often consider outcomes such as the avoidance of surgery or pain equally or more important than OS in some treatment settings^[6]. HTA bodies and payers can perceive patient reported outcomes (PROs) as more subjective, a point of difference that is reflected in the regional variations in the way PRO evidence is reviewed and considered in global HTA decision-making^[6]. This lack of alignment contributes to a lack of clarity around PRO requirements, reinforcing uncertainty among stakeholders.

Towards stakeholder alignment on alternative oncology-relevant endpoints

Overcoming the uncertainties and inconsistencies limiting broader adoption of alternative oncology-relevant endpoints requires concerted efforts from all stakeholders and a more harmonized approach towards their use^[4][6]. There is growing consensus that, by working together, the oncology community can move closer towards establishing sets of appropriate endpoints for specific cancer types and stages that have wide buy-in from regulatory authorities, reimbursement bodies, pharmaceutical developers, and patients themselves.

A key step towards this goal will be agreeing upon the endpoints that matter most to patients, which will almost certainly differ by cancer type and stage^[4][6]. For example, while extending survival may remain a priority in treatment settings with poor prognoses, for cancers where prognosis is improving, disease progression and quality of life may prove more valuable. Once alignment is reached on which outcomes are most valuable to patients, appropriate endpoints and PROs should then be defined through consultation with clinicians and healthcare professionals^[6].

There also exists an opportunity for greater harmonization in the methodologies used to validate endpoints and generate data^[4][6]. This is particularly important for PROs where there is lack of standardization in data collection methods, analysis and interpretation. Alignment on the levels of uncertainty that are acceptable to regulatory and HTA decision-makers and other stakeholders is also important, requiring greater transparency on the evidence needed to support regulatory approval and reimbursement in specific treatment settings^[4][6]. Much work has already been undertaken to establish the surrogate and standalone value of alternative oncology-relevant endpoints. However, the use of real-world evidence and other health economics and outcomes research (HEOR) studies to evaluate the long-term clinical and economic impact of treatments may help accelerate efforts to bridge these gaps^[6].

Global HTA bodies and professional organizations are already taking steps towards a more harmonized approach to assessing the surrogate and standalone value of non-OS endpoints. For example, an ongoing collaboration between HTA bodies including the National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC) and Canadian Agency for Drugs and Technologies in Health (CADTH) is developing methodological guidance and a new joint scientific advice procedure on the use of surrogate outcomes for cost-effectiveness analysis^[8]. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) has also established a taskforce to set good practices for surrogacy evaluation and validation of the relationships between outcomes informing HTA decisions^[9]. These initiatives run alongside broader efforts to harmonize HTA decision-making processes within the European Union under Joint Clinical Assessment, providing an opportunity to promote greater standardization around non-OS endpoints^[10][11].

By supporting more transparent and consistent approaches for the evaluation of alternative oncology-relevant endpoints, these programs have the potential to promote more predictable outcomes in HTA decision-making – a necessary step towards building confidence in the value and suitability of alternative endpoints in clinical trial design.

Looking beyond overall survival

Overall survival remains an important measure of the value of cancer therapies, yet there exists a growing role for oncology-relevant endpoints beyond this ‘gold standard’. By considering patients’ needs, addressing uncertainties, and building consensus around the best outcomes to use in specific treatment settings, oncology-relevant endpoints beyond OS have the potential to facilitate faster and more cost-efficient access to novel cancer treatments.

Clarivate has supported our clients bring the next generation of innovative oncology treatments to market, empowering early-stage R&D and robust clinical trial design, through to navigating regulatory and market access pathways. Within Clarivate’s Evidence, Value and Access consultancy, our reimbursement dossiers, value stories, and objection handlers have supported clients achieve their market access goals in breast cancer, bladder cancer, leukemia and beyond, and our team have expertise with novel technologies such as CAR-T therapies. To learn more about our capabilities and how we can support you, please get in touch here.

This post was written by Richard Massey, Director, Value Communication and Clara Ricci, Senior Medical Writer.

References

^[1]Delgado, A. and A.K. Guddati, Clinical endpoints in oncology – a primer. Am J Cancer Res, 2021. 11(4): p. 1121-1131.

^[2]Cimen, A., et al., Shifting perspectives on the value of non-OS endpoints and PROs: Considerations across stakeholder groups to support oncology HTA decision-making. Journal of Clinical Oncology, 2023. 41(16_suppl): p. e13646-e13646.

^[3]McKee, A.E., et al., The role of the U.S. Food and Drug Administration review process: clinical trial endpoints in oncology. Oncologist, 2010. 15 Suppl 1: p. 13-8.

^[4]Fameli, A., et al., Looking Beyond Survival Data: How Should We Assess Innovation in Oncology Reimbursement Decision Making. Values & Outcomes Spotlight, 2023. 9(5): p. S5.

^[5]IQVIA report, Evolving oncology endpoints – a new horizon for health outcomes 2021.

^[6]European Federation of Pharmaceutical Industries and Federations report, Improving the understanding, acceptance and use of oncology–relevant endpoints in HTA body / payer decision-making 2023

^[7]Grigore, B., et al., Surrogate Endpoints in Health Technology Assessment: An International Review of Methodological Guidelines. PharmacoEconomics, 2020. 38(10): p. 1055-1070.

^[8]NICE, International health technology assessment collaboration expands

^[9]ISPOR, Surrogate Endpoint Statistical Evaluation for HTA Decision Making

^[10]European Commission, Questions and Answers: Adoption of Regulation on Health Technology Assessment

^[11]European Commission, Health Technology Assessment

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As a result, 2023 saw an upsurge in merger and acquisition (M&A) and deal activity. According to BioWorld, M&A values in 2023 jumped 80% over 2022, and deal values reached BioWorld’s highest level ever recorded.

Doubling down on strategic therapeutic areas

Pharma once again finds itself having to narrow its sights on partnerships that deliver the next blockbuster and enable differentiation from the competition—all while navigating increasing regulatory scrutiny and shifting patient and payer expectations.

A prime example of strategic spending is Merck & Co./MSD, which continued its spending spree to strengthen its oncology portfolio. Following high-dollar deals in 2022 for antibody drug conjugates (ADCs) in the oncology space with Mersana Therapeutics and Kelun-Biotech, Merck/MSD once again led biopartnering activity in 2023. This time, the company paid top dollar for ADCs targeting solid tumors from Daiichi Sankyo, with the value of this single deal equaling all of its 15 deals in 2022. Other oncology-related deals for Merck/MSD included its acquisitions of Image Biosciences Inc and Harpoon Therapeutics.

In the neuroscience space, Bristol Myers Squibb acquired Karuna Therapeutics to gain access to KarXT. Initially under regulatory review to treat schizophrenia, KarXT is also being investigated for Alzheimer’s disease psychosis, Alzheimer’s disease agitation and bipolar I disorder. The acquisition complements BMS’s existing programs tackling neurodegenerative and neuromuscular diseases, including 20 programs in the discovery space and five in the clinic. Contributions to these programs come from BMS’s partnership with Evotec SE for neurodegeneration therapies, which the company renewed for the second time in 2023 at a value that landed the deal in the top 10 for the year.

Extending revenue through biologics

Under the IRA, small molecule drugs become eligible for price negotiation after nine years, while biologics are granted a safe harbor of 13 years. This could further fuel interest in ADCs and other antibodies for companies looking to maximize revenue, and ADCs and polyspecific antibodies have featured in many of the recent top deals.

The top ADC deal was that between Merck/MSD and Daiichi Sankyo. Coming in second place, Bristol Myers Squibb bolstered its oncology pipeline, which previously consisted of only two acquired ADCs, through ADC-related deals with Mainland China-based SystImmune, a Sichuan Biokin Pharmaceutical Co Ltd subsidiary, and with Germany-based Tubulis. This represents the first partnership for Tubulis, moving its ADC technologies closer to clinical proof of concept and opening the doors for future collaborations.

Amsterdam-based Synaffix B.V., a Lonza company, had a busy 2023. It entered multiple partnerships to provide access to its clinical-stage antibody conjugation technology, GlycoConnect, and ADCs developed from the platform. Two of its five agreements, with MacroGenics Inc and Amgen, fell within the top-valued deals for 2023, and other lucrative deals occurred with SOTIO Biotech, Hummingbird Bioscience and ABL Bio Inc. These add to the company’s previous licensing agreements with Genmab A/S, Kyowa Kirin Co Ltd, ProfoundBio, Innovent Biologics Inc, ADC Therapeutics SA, Emergence Therapeutics AG and others.

With regulatory approvals of bispecific antibodies reaching double digits, biopharma is building on the ability of these therapies to overcome the limitations of monoclonal antibodies by continuing to innovate and partner in this space. Two of the top five polyspecific antibody deals in 2023 involved trispecific or tetraspecific antibodies — between Mainland China-based WuXi Biologics and GSK plc and between Celltrion Inc and Cyron Therapeutics Co Ltd, both for oncology targets.

Other partnerships of note include one for a couple of Shanghai-based Elpiscience Biopharma Ltd’s preclinical bispecific antibody assets, licensed by Tokyo-based Astellas Pharma Inc, with the option to license two more. Both products are based on Elpiscience’s Bispecific Macrophage Engager (BiME®) platform and will undergo collaborative early-stage research between the two companies. This continues work between the companies that started with a shared interest in the concept of macrophages and a desire to investigate Claudin18.2 as a target for the BiME platform.

In addition, BioNTech signed a deal with Biotheus Inc for exclusive options to a preclinical-stage bispecific antibody candidate for oncology. This adds to the multiple high-value ADC deals BioNTech signed in 2023 for oncology targets and aligns with its plans to diversify and grow its pipeline of oncology candidates to include ADCs, cancer vaccines, cell therapies and more.

Partnering at the heart of innovation

Pharmas rely on biotechs to fill gaps in expertise, technology and resources, which will continue to drive opportunities for biotechs to partner or pursue acquisition to further their assets and continue innovation. As pharmas are increasingly selective about how they spend their money, biotechs would benefit from aligning their strengths with pharma companies’ priorities.

For more on how pharmas and biotechs are navigating a challenging financing environment, please view our recent webinar, Raising money in uncertain times: How private life science companies can overcome fundraising challenges.

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Discover how the Web of Science Research Intelligence platform will revolutionize research evaluation by driving responsible innovation and demonstrating societal impact.

At Clarivate, we recognize the pivotal role that research plays in shaping the future. That’s why we’re excited to announce the development of Web of Science Research Intelligence, a next-generation software solution powered by AI that will empower researchers to accelerate breakthroughs and research institutions to better measure and showcase the impact of their research.

Empowering innovation in a changing landscape

In today’s rapidly evolving research landscape, institutions face increasingly complex challenges that demand innovative solutions and strategic approaches. Clarivate conducted extensive research throughout 2023 to better understand current priorities and pain points among university research office executives. In addition to the Research Offices of the Future report from Research Professional News, product teams also conducted a series of in-depth qualitative interviews with leaders around the world. From mounting pressures to secure research funding to an urgent imperative to demonstrate societal impact beyond publications, the hurdles are diverse and ever present. University leaders and researchers must navigate increasing cost pressures, adapt to new technologies such as AI, and maintain the integrity of research outputs to remain competitive and relevant. Web of Science Research Intelligence represents the next generation of tools designed to empower institutions to meet these challenges head-on.

Currently being developed in partnership with leading academic institutions, Web of Science Research Intelligence is an AI-native platform that embodies a vision centered on three pillars: unification, innovation and impact. It seamlessly integrates funding data with research outputs that include publications, patents, conference proceedings, books, policy documents and more. Based on these data, the platform identifies relevant funding opportunities within emerging research areas, equipping institutions and researchers to innovate.

• A conversational assistant powered by generative AI enables all users to gain insights and create qualitative narratives for more balanced impact assessment, from data scientists to those with limited analysis experience.
• Tailored recommendations for collaboration and funding help early career researchers build their networks and all researchers position themselves to win.
• A new framework for measuring societal impact beyond traditional citation metrics will empower researchers and institutions to showcase the broader impacts of their work.

Unlocking the societal benefit of research 

Research funders and policymakers are increasingly placing a premium on the societal benefits derived from research investments. This shift underscores the growing imperative for research institutions to deliver findings that not only meet rigorous academic standards but also yield tangible contributions to the public. The Institute for Scientific Information (ISI) recently discussed the challenges of assessing the societal impact of publicly funded research and announced the forthcoming release of our proposed framework. With Web of Science Research Intelligence, institutions gain the ability to unearth and spotlight their sociological, economic, environmental, political, technological and sustainability impact at various levels — be it at the organizational, departmental, or researcher level — and the flexibility to define their own impact. This capability not only enriches the research narrative but also strengthens the case for continued support and recognition in an increasingly competitive landscape.

Web of Science Research Intelligence isn’t only about driving innovation; it is also about enhancing institutional efficiency and effectiveness. Recent studies have underscored the inefficiencies inherent in traditional research management processes. Researchers and administrators spend countless hours re-keying publication and grant information into university systems, while only a fraction of institutions effectively utilize data for decision-making. By streamlining administrative tasks of collecting, unifying and tracking faculty research outputs, our platform reduces friction so that researchers and administrators can focus on advancing knowledge and driving change— a fundamental aspect of our mission.

Shaping the future together

As part of our commitment to innovation, we recognize the invaluable role of collaboration with the research community. That’s why our approach to developing Web of Science Research Intelligence is centered on partnerships with research institutions. This partnership not only fosters trust in the technology and its applications but also ensures that our solution remains relevant and impactful in meeting the evolving needs and addressing the most pressing challenges of the research community.

“The University of Manitoba looks forward to being a strategic partner in the development of next-generation methodologies for assessing global research performance and emerging trends.”

“We are pleased to partner with Clarivate and peer institutions in the development of a novel technological solution to harness the power of research intelligence. Web of Science Research Intelligence has the potential to transform the way we map, fund and measure research opportunities and societal impact. This collaboration is a strategic move to integrate our collective expertise to benefit the global research enterprise.”

As we continue to develop Web of Science Research Intelligence in collaboration with academic partners around the world, we’re excited about the impact it will have on the future of research. With our platform, institutions will not only enhance their funding prospects and global visibility but also cultivate stronger research teams and solidify their position as leaders in innovation and academia.

We invite you to join us in shaping the future of research with Web of Science Research Intelligence. Together, we can unlock new opportunities, drive responsible innovation and shape the future of research and research management.

Learn more about Web of Science Research Intelligence here. To become an early adopter, contact us at wosripartners@clarivate.com

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For some products, the point of failure is a single oversight or miscalculation. Others stumble across multiple hurdles before finally calling it quits. However, not all product missteps end in outright failure –some companies are able to learn from their mistakes in real time, salvage their development efforts and emerge triumphant.

From each of these scenarios, valuable lessons can be learned and folded into the next development cycle. A review of multiple product setbacks and failures by Clarivate analysts revealed that they stemmed from a few common reasons:

• Lack of early communication and collaboration across departments: Scientific discovery alone is often not sufficient to guarantee market success, yet R&D and early-phase trials continue to operate independent of clinical development, regulatory, commercial and market access teams. Without insight from across the company about what will drive success when the product emerges from the lab, issues occur when it can be too late or cost-prohibitive to implement countermeasures. Early due diligence informs a program design that addresses concerns across the entire development lifecycle.
• Misinterpreting or not anticipating stakeholder expectations. It is not sufficient to assume that what worked during the last product market launch will meet the ever-evolving priorities of patients, physicians, governments, regulators and payers at the next product launch. Furthermore, what is considered appropriate for one country or region might not apply to others. Keeping a finger on the pulse of stakeholder demands helps identify products (molecules, platforms and devices) that answer unmet needs; establish clinical trial designs to collect the data needed to demonstrate efficacy, safety and benefit beyond merely clinical outcomes; and communication strategies to effectively differentiate the product.Even for biotech companies looking to be acquired after promising early-phase results, investors and potential partners are seeking confirmation that the product will be viable once it reaches the market—will it be acceptable to use, considered reimbursable, and does the value outweigh its risks? These stakeholders want to avoid inheriting poor choices that have already become part of the fabric of the product development process.
• Not addressing red flags as they occur. Early regulatory feedback about additional data needed, competing developments in the same drug class/therapeutic area and criticisms of pricing are all examples of pending roadblocks that companies have ignored along the way to submission and market launch. The cost of continuing, in both resources and company reputation, was often higher than if the companies had paused to re-evaluate and adjust their strategies or to make crucial go/no-go decisions earlier.

Reviewing and analyzing past failures and recoveries highlight the types of data that can inform future product and clinical trial design as well as commercial launch, helping future-proof product candidates from early R&D through commercialization. These include real-world data about:

• Patient unmet need
• Biomarkers and disease/patient segmentation
• Clinical trial sites in patient and physician-dense areas
• Safety and efficacy signals of possible concern
• Geographic differences in regulatory requirements
• Evolving government policies and initiatives
• The clinical and competitive landscape surrounding a developmental product
• How to accurately value product candidates to secure funding and inform pricing and market access strategy

Hear from Clarivate analysts about specific examples of products that were overlooked, failed to gain market approval or struggled at launch in our Learning the Lessons of Failure: How to improve the economics of life sciences R&D webinar and how these roadblocks could potentially have been overcome with earlier, better-informed planning and monitoring.

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In this era of real-world data (RWD) and precision medicine, the quest to unlock the mysteries of rare diseases and tailor treatments to individual patients has never been more promising. Data from a rising tide of sources can empower pharma executive decision making from R&D, clinical studies, health outcomes, drug safety, and market access.

With the wealth of data generated from diverse sources comes the challenge of extracting meaningful insights from the pool of available databases and translating them into actionable strategies. Where the amount of unstructured data is enough to drown you, think of machine learning as your personal flotation device that, when used correctly, can pull you safely to shore.

This begs the question: What computational and analytical tools are available for mining and interpreting rare disease data, and how can companies bridge the gap between data generation and actionable insights?

This subject is discussed in a forthcoming white paper from Clarivate. Hemanth Nair, Director of Real World Evidence Engagement and Innovation at Clarivate, discusses how to apply machine learning to RWD to make foundational decisions on the course of clinical trials, site recruitment and patient identification, while giving real life examples from a recent project with a rare disease client.

From data deluge to actionable insights

Computational tools, databases and platforms are increasingly being used for the enhancement of rare disease therapies, including data mining, data integration, data standardization and quality assurance, as well as visualization and interpretation. With this in mind, what is available, and why should you consider it as part of your rare disease product development?

• Data mining

Machine learning algorithms, including supervised and unsupervised learning methods, can uncover patterns, correlations, and associations within complex datasets. AI-powered approaches such as deep learning, natural language processing (NLP), and neural networks enable advanced data analysis and predictive modeling, offering insights into disease mechanisms, patient outcomes, and treatment responses.

Bioinformatics tools facilitate the analysis of genomic data, including DNA sequencing, gene expression profiling, and variant annotation.

Genomics databases and resources ̶ such as NCBI’s GenBank, the DNA DataBank of Japan, and the European Nucleotide Archive ̶ provide access to annotated genomes, genetic variants, and functional annotations for rare disease research.

• Data integration

Data integration platforms enable the aggregation and harmonization of heterogeneous datasets from disparate sources, including electronic health records (EHRs), patient registries, and omics data.

These platforms facilitate comprehensive data analysis and enable researchers to correlate clinical, genetic, and molecular information, offering a holistic view of disease biology and patient phenotypes.

There are several platforms and solutions available in the market catering to data integration needs in the pharmaceutical industry, each with its own unique features and capabilities. It’s essential to evaluate these platforms based on specific requirements and use cases to determine the best fit for a particular organization’s needs.

• Data standardization and quality assurance

Establishing standardized protocols for data collection, curation, and validation ensures data integrity and interoperability across different platforms and institutions. The Clinical Data Interchange Standards Consortium (CDISC), for example, develops and promotes global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.

CDISC standards cover various aspects of clinical research data, including study design, data collection, data representation, and data exchange. It has standards like SDTM (Study Data Tabulation Model) for organizing and standardizing clinical trial data, ADaM (Analysis Data Model) for analysis datasets, and CDASH (Clinical Data Acquisition Standards Harmonization) for standardizing case report forms (CRFs) and data collection.

Implementing robust quality assurance processes mitigates the risk of errors and inconsistencies, enhancing the reliability and trustworthiness of data-driven insights. Tools are available that have been specifically designed for regulated industries and helps companies to maintain product quality, adhere to regulatory requirements, and improve overall operational efficiency through standardized and automated quality processes.

• Data visualization and interpretation tools

Data visualization tools such as interactive dashboards and heatmaps facilitate the exploration and interpretation of complex datasets, enabling stakeholders to identify trends, outliers, and actionable insights. Advanced analytics platforms offer customizable analytics pipelines and visualization options, empowering users to extract meaningful insights from raw data and communicate findings effectively.

Tools such as RapidMiner, SAS Visual Analytics, Tableau, and TIBCO Spotfire are all popular among the biopharmaceutical and medical device industries to visualize, analyze, and interpret data from various sources.

For more on how Clarivate uses AI and machine learning to help companies develop innovative medicines, devices and diagnostics, generate knowledge and safeguard intellectual property, please visit us here.

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In the research and development space, we help companies advance their drug discovery, preclinical proof-of-concept, and regulatory activities.  Clarivate’s translational science expertise, regulatory and commercial experts and assets combine to complement client teams in generating long term value.

I’m therefore particularly proud of this newly published case study where Gedeon Richter and Clarivate worked closely to transform regulatory workflow, connect data and improve decision making.

Our client is a major pharmaceutical company headquartered in Budapest, Hungary, with an expanding presence in Western Europe, Mainland China, Latin America and Australia. Its product portfolio covers many important therapeutic areas, including women’s healthcare, central nervous system and cardiovascular health.

53% of pharma CEOs report regulatory changes as a top disruptive trend*

Gedeon Richter had a need to streamline regulatory monitoring and impact assessments. Each day, thousands of regulatory and industry-related documents are released from different regions and companies all over the world. Before partnering with Clarivate, teams would spend hours manually triaging these regulatory documents to identify and communicate impacts across their organization.

This required a significant amount of time to sift through multiple regulatory intelligence sources to identify and locate essential data. Gedeon Richter staff would travel to the sites of EMA (European Medicines Agency), FDA (Federal Drug Administration) and other regulatory authorities to manually review updates in regulations or guidelines. These documents would be downloaded and sent manually via email to subject matter experts.

Gedeon Richter is one of the earliest subscribers to the Clarivate Regulatory Intelligence Tracking Application, an industry leading solution and companion to Cortellis Regulatory Intelligence.  This end-to-end solution helps organizations manage regulatory intelligence by providing a single source of truth, unifying and making that data more actionable.  Our consultants have helped empower professionals at Gedeon Richter to think and act more strategically by providing:

• Customizable dashboards that deliver the regulatory update data specific to regions and topics of interest
• Solutions powered by AI that automates the daily processing of new regulations and legislation
• A source for all departments to complete and view impact assessments.
• A notification and alerting system that keeps their experts up to date on the latest regulatory requirements around the world
• A searchable storage solution that consolidates regulatory updates

The impact of a trusted partnership

Now, with unified data sources from Clarivate, Gedeon Richter has more visibility into regulatory changes and can reinvest time on higher value activities such as actions and impact assessments.

Technology and regulatory consultants from Clarivate provided full support during Gedeon Richter’s transition into the tracking application.

“Clarivate has been very approachable and responsive to taking our business needs into consideration when working with the tracking application. We are now able to efficiently triage and manage our regulatory alerts, send out newsletters with ease, and so much more!”

Our worldwide roster of clients can call upon a 300-strong team of practice leaders, therapy area specialists, data scientists, industry experts and analysts who take the time to understand client needs so that we can co-create transformative solutions like this Gedeon Richter example.

If you would like to discuss your 2024 plans with any of our R&D, commercialization or technology enablement teams, please connect with our experts here.

*Source: https://www.nature.com/articles/d41573-022-00001-9

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R&D productivity fell in 2022, but late-phase cancellations are also trending down

The rise and fall of R&D productivity across the global biopharmaceutical industry is a well-documented and much discussed topic, with industry commentators quantifying productivity in many ways (e.g., forecast peak sales per asset versus the cost of developing an asset or an output measure such as the number of global first world launches).

The common thread in all these different metrics is that R&D productivity is measured as a function of an input – for example, R&D expenditure — versus an output, such as sales of newly launched products. In addition, R&D productivity analyses are in some way associated with actual or future launches or a consequence of the launch, such as resulting sales. So, a simple and obvious surrogate for R&D productivity, which considers an output component only, is the number of New Molecular Entities (NMEs) launched annually.

Figure 1 illustrates the trend in the number of NMEs first launched onto the world market between 2013 and 2022. Looking at NMEs launched globally in 2022 paints a gloomy picture at first sight, with a 28% drop from 2021 to 2022. While some industry observers read this drop as a clear decline in productivity, others take a more optimistic view, attributing the decline to FDA submission calendar fluctuations and noting that 2022 numbers were not very different from the ten-year average. In fact, the number of NMEs has grown by 65% between 2013 and 2022.

Figure 1: Number of NME launches from 2013 to 2022

Analyses from the 2023 R&D Factbook also indicate that the number of late phase terminations has consistently declined in recent years. Together, these trends paint a positive picture for the biopharmaceutical industry, suggesting that the industry is getting better at “doing more with less” and progressing only the more promising compounds, thereby improving productivity.

Spend is growing, but ROI is TBD

However, when looking at the potential commercial value of this R&D activity, some challenges remain.

R&D spend is steadily growing and is expected to reach approximately $200 billion by 2025. This amounts to approximately 20% of sales revenues which are reinvested into developing pipelines. However, only 10% of global biopharmaceutical sales were derived from products launched in the preceding five years, the rest of revenues coming from established products. CMR analysis suggests that this trend is likely to continue in the near term.

The industry is focusing on newer technologies and modalities to drive innovation, including cell and gene therapies, antibody drug conjugates, AI and machine learning, along with novel targets, predictive biomarkers and newer, more complicated study designs. However, their full impact on value remains to be realized.

Altogether, the data highlight an improvement in the volume of R&D productivity, while the value of this innovation remains uncertain.

The 2023 CMR International Pharmaceutical R&D Factbook features metrics and analyses on R&D productivity and many other key topics relevant to the biopharmaceutical industry, such as R&D resources and pipelines, patents and generic drugs. Learn more about purchasing it here.

For over 20 years, CMR International has been a trusted partner to the largest and most innovative pharmaceutical companies to help them assess R&D productivity and provide insights and decisions on industry trends. To learn more about how Clarivate and CMR International help pharmas future-proof their portfolios, please visit us here.

Jasmin Mehta is a Senior Manager within the Life Science Professional Services team at Clarivate. She has over 19 years of experience within Pharmaceutical R&D analytics and currently leads a broad array of assignments including Pharma R&D industry benchmarking, competitive landscape analysis and building business intelligence platforms within the R&D development space. She has extensive experience working with the business intelligence teams of leading pharmaceutical companies on topics such as R&D productivity , portfolio risk and protocol complexity. Prior to joining Clarivate, she has held a consulting role within the market research and data analytics team of a strategy consulting firm.

Jasmin has a Masters degree in Corporate Governance from Kingston University, London and a Bachelors degree in Economics and English Literature from the University of Mumbai.

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According to the Gartner report, “By 2025, R&D organizations that use IP analytics to conduct continuous technology intelligence will be 80% more likely to outperform direct competitors in revenue growth.”

That is also why Clarivate offers an integrated IP research and management solution that combines Innography IP intelligence with our IPfolio IP management software to provide R&D teams with a powerful solution for analyzing and managing inventions throughout the innovation lifecycle.

Two products, one solution

With Innography, IP and R&D professionals are able to explore the world’s patent data to analyze white space opportunities, evaluate state of the art, and find collaborators and development partners. AI-powered semantic search allows users to conduct research using a description of an existing or proposed invention. Powerful analytics tools including text clustering, heat maps and landscape visualizations help users expand or refine their analysis to capture the right insights to inform critical decisions. Integrated access to Derwent World Patents Index (DWPI) accelerates review of patent documents with abstracts that clearly state an invention’s novelty, use and advantage.

IPfolio enables R&D teams to leverage the power of connected data and services for innovation management throughout the entire IP lifecycle. This powerful and flexible SaaS solution simplifies innovation management and maximizes operational efficiency with process automation and embedded tools for seamless collaboration with stakeholders across the IP value chain. Enriched Clarivate data and embedded analytics help users easily uncover actionable insights and create custom reports.

The power of integration

The full value of these solutions for R&D lies in their integration. Records in both solutions are connected by custom fields.

An IPfolio user can apply a custom field to patents that may present a freedom-to-operate risk for a new product or a patentability obstacle for a new invention. The R&D user can then find the records matching their project using the custom field and analyze and review the documents in Innography. Private matters, such as invention disclosures and unpublished applications, can be synced between IPfolio and Innography. This enables R&D users to search and analyze relevant private publications alongside published patent records.

With Innography’s AI-powered semantic search engine, R&D users can enter a simple description of their invention and retrieve relevant documents from both IPfolio and Innography. This is extremely useful for assessing whitespace around an invention, identifying internal and external collaborators, and spotting potentially duplicative internal inventions.

Start with an expert assessment

The Gartner report also offers some recommendations for evaluating IP research and management solutions for R&D teams, including this recommendation: “Assess your current processes to isolate workflow steps where bottlenecks frequently occur or are likely. Use the insight gained from this analysis to compile a list of the desired software solution capabilities.”

Clarivate can help. With our IP Diagnostic Consulting service, Clarivate IP experts evaluate the IP management processes, identifying opportunities for improving both efficiency and effectiveness. Our team focuses on best practices in four key areas: People, Process, Information and Technology. In our experience, implementing the recommended changes can yield significant improvements. Our IP Diagnostic Consulting is the first step toward creating a modern and efficient IP management function.

Looking to give your R&D team every advantage when researching and managing innovations? Contact us today to learn more about our integrated solution for R&D or to schedule your IP Diagnostic.

Gartner, Market Guide for Intellectual Property Management Software With R&D-Specific Use Cases, Svetlana Golden, Shradha Sapra, 22 August 2023

GARTNER is a registered trademark and service mark of Gartner, Inc. and/or its affiliates in the U.S. and internationally and is used herein with permission. All rights reserved. Gartner does not endorse any vendor, product or service depicted in its research publications, and does not advise technology users to select only those vendors with the highest ratings or other designation. Gartner research publications consist of the opinions of Gartner’s research organization and should not be construed as statements of fact. Gartner disclaims all warranties, expressed or implied, with respect to this research, including any warranties of merchantability or fitness for a particular purpose.

The post Clarivate named as a Representative Vendor in the 2023 Gartner® Market Guide for Intellectual Property Management Software With R&D-Specific Use Cases report appeared first on Clarivate.

The treatment of diabetes is a perfect example of this. While there is still no cure for diabetes, the availability of increasingly effective medicines over the last century changed it from being considered a terminal diagnosis, particularly for those diagnosed in childhood, to a manageable, chronic disease.

Insulin: from radical innovation to standard of care

The key radical innovation that changed the course of disease for people with diabetes was the medical use of insulin in the 1920s. Before this, diabetes was managed with calorie restriction, which provided some benefit for those diagnosed in adulthood (those with what we now know as type 2 diabetes [T2D]) but did little for patients diagnosed in childhood (those with what we now know as type 1 diabetes [T1D]), who often died within days or weeks of diagnosis.^[2] Insulin provided a treatment option that allowed those with access to treatment to live for many years after diagnosis.

Although an incredible breakthrough, initially, insulin was not the effective, well tolerated, and relatively convenient treatment that it is today. It was derived from animal sources and its use was complicated by issues of insulin resistance and supply.^[3] Further innovation came with the introduction of human insulin and recombinant technology in the 1960s and 1970s, which helped to address these issues and make insulin more accessible and easier to use.^[2],^[3] Since these radical changes, a series of incremental innovations has resulted in availability of insulins that not only provide improved clinical outcomes, but also have varying durations of action to allow optimal glycaemic control while minimising the daily number of injections needed.^[2] Advances in blood glucose monitoring and in the delivery of insulin through insulin pens and, more recently, pumps have also helped to make diabetes management easier for patients. Despite the advances in insulin therapy, a treatment burden remains, which can deter people from initiating and adhering to it.^[4]

It’s not all about insulin

Innovation in the treatment of diabetes has not been limited to insulin. For those with T2D (approximately 90% of people with diabetes^[5]), several additional treatment options are available, which may delay the need for insulin. For example, among other treatments, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can be used for the treatment of T2D prior to initiation of insulin and can also be used in combination with insulin to improve disease control later in the treatment pathway.^[6]

GLP-1 RAs provide another example of the benefits that incremental innovation can bring to patients. In addition to differences in efficacy and cardiovascular benefit seen within the GLP-1 RA class, incremental innovation within the class has resulted in substantial reductions in the burden of treatment on patients. The first GLP-1 RA used for diabetes (short-acting exenatide) became available in 2005 (US)/2006 (Europe) and required twice-daily injection. Since then, two GLP‑1 RAs requiring only once-daily injection have become available, followed by three which require only once-weekly injection (Figure 1).^[7] Most recently, the first orally administered GLP-1 RA has become available, meaning that willingness and ability to self-inject is no longer a pre-requisite for GLP-1 RA therapy.^[7],^[8] These advances have the potential to improve patient uptake of and adherence to effective treatments, thereby improving outcomes.

Figure 1: Timeline of GLP-1 RA development^[9],^[10]

Abbreviations: EMA, European Medicines Agency; US FDA, United States Food and Drug Administration.

What’s next in diabetes?

Gene and stem cell approaches may eventually offer a cure for diabetes.^[2] In the meantime, incremental innovation continues to provide treatment advances. For example, alternative formulations of insulin are expected to become available, including those requiring only once-weekly administration^[11] and, potentially, even oral administration.^[2] In addition, building on the success of the GLP-1 RA class, a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA has recently become available and may provide even greater disease control than GLP-1 RA alone.^[12]

While the search for a cure continues, a combination of radical and incremental innovation continues to dramatically alter the outlook for people with diabetes, not only improving outcomes, but also reducing the burden of treatment. The radical steps in innovation are, of course, necessary, but the impact of building on these steps through incremental innovation should not be underestimated. Ultimately, when it comes to reimbursement for a medicine, it is not the level of innovation but the level of patient benefit that matters most.

At Clarivate, we recognise that demonstrating value to market access stakeholders isn’t always straightforward, particularly when a product is adding to an existing treatment class. Such value demonstration requires an integrated approach to evidence generation planning, and the development of value propositions that are tailored to specific patient populations and unmet needs in a changing treatment landscape.

The Clarivate Value Communication team, part of Evidence, Value and Access Consulting, specialises in the development of robust and compelling value communication materials, reimbursement dossiers, objection handlers and publications. We also have extensive experience in primary payer and KOL research, and in developing interactive client workshops and training. To learn more about our capabilities and how we can support you, please get in touch at https://clarivate.com/products/life-sciences-and-healthcare-consulting-services/evidence-value-access-consulting/.

This post was written by Sophie Doran, Senior Director, Head of Medical Writing, and Sophie Streeton, Principal Medical Writer.

References

^[1]Hofmann et al. A review of current approaches to defining and valuing innovation in health technology assessment. Value in Health. 2021; 24(12):1773-1783.
^[2]Buse et al. 100 years on: the impact of the discovery of insulin on clinical outcomes. BMJ Open Diabetes Research and Care. 2021; 9:e002373.
^[3]Hirsch et al. The evolution of insulin and how it informs therapy and treatment choices. Endocrine Reviews. 2020; 41:733-755.
^[4]Zhu and Harris. Therapeutic inertia in people with type 2 diabetes in primary care: a challenge that just won’t go away. Diabetes Spectrum. 2020; 33(1):44-49.
^[5]International Federation of Diabetes. Diabetes Atlas, 10^th 2021.
^[6]American Diabetes Association. Standards of Medical Care in Diabetes. 2023.
^[7]Trujillo et al. GLP-1 receptor agonists: an updated review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism. 2021; 12:1-15.
^[8]Aroda et al. A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Reviews in Endocrine and Metabolic Disorders. 2022; 23:979-994.
^[9]Food and Drug Administration. Drug approvals and databases. Available at: https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases [Accessed November 2023].
^[10]European Medicines Agency. Medicines. Available at: https://www.ema.europa.eu/en/medicines [Accessed November 2023].
^[11]Rosenstock et al. Weekly icodec vs daily glargine U100 for type 2 diabetes without previous insulin. New England Journal of Medicine. 2023; 389:297-308.
^[12]Frias et al. Tirzepatide versus semaglutide once-weekly in patients with type 2 diabetes. New England Journal of Medicine. 2021; 385:503-515.

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The global Clarivate clinical outcome assessment team is comprised of health psychologists and outcomes researchers who have extensive methodological and commercial experience. Our deep and broad knowledge of therapy areas such as oncology, immune disorders, respiratory, psychiatry, CNS, autoimmune, infectious diseases, pain, and women’s health enables sponsors to make informed decisions when selecting, developing and validating clinical outcome assessments (COAs) for use in clinical trials.

In this article, we highlight two case studies which address challenges faced by sponsors looking to incorporate COAs into clinical trials for a number of therapy areas. Data and insights gleaned from these projects have most recently been presented at industry conferences and events, including ISPOR.

The purpose of clinical trials is to understand the efficacy and safety of treatments for the patients who need them. To understand treatment efficacy, it is necessary to measure the impact of the treatment on patients’ signs/symptoms, functioning and overall health-related quality of life. A clinical outcome assessment is a measure that describes or reflects how a patient feels, functions or survives.

COAs include patient-reported outcome (PRO) measures, clinician-reported outcome (ClinRO) measures, observer-reported outcome (ObsRO) measures and performance outcome (PerfO) measures. Including fit-for-purpose measures in clinical trials can allow sponsors to generate critical evidence for regulators to evaluate the efficacy and safety of their product, and after approval these data can inform cost-effectiveness analyses for payer decision making.

Qualitative data and quantitative data are required to develop/modify COAs and demonstrate their measurement properties. These data can take several years to generate, requiring methodological expertise, deep disease understanding, substantial input from patients and other key stakeholders (e.g., clinical experts), and converting regulatory guidance into practical application.

The landscape around COAs is fast evolving

The evidence standards that a COA must meet to support key clinical trial endpoints have become increasingly stringent in recent decades, following the introduction of the United States Food and Drug Administration (FDA) Patient Reported Outcomes (PRO) draft guidance in 2006, followed by the full guidance in 2009. More recently, the FDA has developed the Patient Focused Drug Development (PFDD) Guidance Series, which provides sponsors with guidance on how to collect and submit patient experience data in medical product development for regulatory decision making. The PFDD series will eventually take the place of the PRO Guidance for Industry.

Last year alone the Clarivate COA team conducted over 300 interviews with patients, caregivers or healthcare professionals. We developed or explored over 100 COAs and achieved ethical approval in multiple countries including the U.S., U.K., Mainland China and Japan. These incorporated a variety of methodologies including literature reviews, patient preferences, exit interviews and FDA dossier development.

Patient focused drug development in alopecia areata clinical trials

The Clarivate COA team worked with a sponsor to develop COAs for evaluating key clinical trial endpoints in alopecia areata clinical trials.

The team interviewed patients and clinical experts to conceptualize the disease experience and develop content valid PROs and ClinROs, with accompanying photo guides to assess disease-defining signs/symptoms. Quantitative data from clinical trials informed the psychometric performance of the COAs and thresholds for interpreting within-patient meaningful change. All data were collated in FDA COA Evidence Dossiers.

Several years of evidence generation culminated in the FDA’s approval of the first systemic treatment for alopecia areata with data from the COAs developed by the Clarivate team was included in the approved labelling. Most importantly, newly approved treatments can address significant unmet needs for patients living with severe alopecia areata. The work, said lead investigator Brett King, Associate Professor at Yale Dermatology, “helped change the landscape of alopecia areata forever.”

A qualitative interview study into the experiences of fatigue and depression in chronic hepatitis B

Our experts helped the client to conceptualize the experience of chronic hepatitis B (CHB)-associated fatigue and depression amongst individuals living with CHB in the U.S. Patients participated in semi-structured qualitative interviews with COA experts, designed to elicit concepts important to measure in individuals living with CHB. The results led to the expansion and refinement of a previously developed conceptual model to document the multifaceted experiences of fatigue and depression for patients living with CHB. These findings can inform a patient-centred PRO measurement strategy for clinical trials in CHB.

Clarivate experts can streamline your clinical development strategy with fit-for-purpose PROs and other COA instruments to support regulatory, communication, and reimbursement strategies. To learn more about COA, our broader evidence, value and access offerings or view our industry expert profiles, please visit our website.

About the author

Helen Kitchen is the Vice President of Clinical Outcome Assessment at Clarivate. Helen has 15 years’ experience of selecting, developing, and validating COAs, including PROs, for pharmaceutical clinical trials.

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