Christian K Schneider, M.D.- Head of Biopharma Excellence and Chief Medical Officer (Biopharma) at PharmaLex
Advanced therapy medicinal products (ATMPs), as they’re called in the European Union and the UK, or cell and gene therapy products (CGTPs) as they are called in the US, have long been considered game changers for the treatment of severe conditions with limited or no current treatment options. Driven by scientific innovations, impressive clinical outcomes, and a succession of new product approvals, the market for such therapies is projected to be worth almost $21.2 billion by 2028. The industry, now considered to have reached ‘adolescence’ by many analysts, also holds great promise in making personalized medicine a reality, and improving global health through wider patient accessibility to suitable treatments.
For all their exciting potential, however, innovative therapies employ a model that is markedly different from conventional development paradigms - and one for which more tailored approaches are needed. The usual clinical development paradigm is very often simply not applicable to ATMP developers, for instance. That’s because these companies are targeting smaller patient populations - often with acute needs for the emerging treatment - with pricing models that may be prohibitive for many payers.
To address and overcome likely challenges, companies need to 1) plan early, building bridges between quality (CMC; chemistry, manufacturing and controls), non-clinical and clinical disciplines; 2) develop a regulatory strategy as soon as drug development begins; and 3) analyze the healthcare landscape to determine the market access model that will provide a strong value proposition for decision makers and payers. Overall, the goal should be to build an agile approach to planning that minimizes delays or risks of failure.
Five Strategies to Minimize Risks and Accelerate Development
Strong strategies are rooted in proper planning. This needs to start on Day One, with an integrated approach that involves quality, non-clinical and clinical disciplines pulling together.
With advanced therapies, there are many complexities to consider in the commercialization process. Patient populations are very often smaller and more targeted and even though that means product quantities can be low, they also have very specific logistical requirements. For example, manufacturing considerations and patients’ lives can depend on the speed at which a product moves from the bedside to the facility and back again, especially in cases where shelf-life is very short.
Although advanced therapies might be potentially transformative, pricing for them may ultimately prove prohibitive for some payers. At the same time, the underlying quality, regulatory, and manufacturing guidelines that apply to traditional drug development must still be considered – and those guidelines can be nuanced depending on country or region, which can make them challenging to navigate.
- Conduct a risk/benefit assessment. New therapies have considerable potential to provide significant treatment options, perhaps even with curative intent, but they also come with significant known and unknown risks, many of which are unique to this product class. Therefore risk, too, needs to be considered from an early stage - with a primary focus on not only safeguarding the patient, but also minimizing risks to healthcare professionals and caregivers. The risk/benefit assessment should be designed as a gate to go/no-go decisions at each stage of development. Sometimes, the “go” will require a change in direction so the process should be agile with an eye toward risk identification, evaluation, and mitigation. That agile approach should apply not only to the biological activity of the ATMP, but also the quality attributes, the manufacturing process steps, and the therapeutic administration procedures.
- Develop an Integrated Product Development Plan (IPDP). For a holistic approach to the creation of an IPDP, all development disciplines such as manufacturing, nonclinical and clinical development as well as regulatory affairs need to be involved. Even for early-stage programs, commercial aspects such as targeting specific countries for commercialization, the competitive environment as well as pricing/reimbursement aspects should all be considered. The IPDP is a living document that will get continually updated as development progresses, promoting organizational prioritization and decreasing time-to-decision. Defining the patient population, and the target stage for a given disease, for example, are important considerations, and these could have an impact on the design of non-clinical studies etc.
- Consider models to scale manufacturing. The path to commercialization should be in view right from Day One. Moving the therapy from the lab to scaling it for supply to patients, which means producing a sterile drug product in sufficient quantities, can be challenging. To ensure scalability without burning cash as you go, organizations must align manufacturing readiness with the regulatory pathway, the patient population, and the dosing that is being pursued.
- Accelerate commercialization with an effective regulatory strategy. There are distinct aspects to the regulatory plan – all happening in parallel – which should evolve as development progresses. These include: 1) documenting the goal, which can be visualized via the Target Product Profile (TPP); 2) keeping pace with competitive therapies; 3) maintaining regular checkpoints with regulatory agencies; and 4) considering regulatory pathways, depending on markets or regions, indication areas, and classification of the therapy. The regulatory strategy should evolve along with development, and as new information about the competitive environment, study results, and interactions with regulatory agencies progress come in.
- Initiate a market access strategy. To gain market access, developers must be able to demonstrate clinical and economic evidence to providers, healthcare decision-makers, and, importantly, payers. Given the complexities of the way healthcare is paid for, it’s crucial to understand who will finance the therapy and the mechanisms by which the care will be reimbursed. Developers must consider strategies that take a more holistic view of patient treatment and provide better real-world evidence, therefore offering a stronger value proposition for decision-makers. This planning must begin at the onset of an idea, during the proof-of-concept phase, so that later considerations on risk-benefit and cost-benefit converge and can be derived from overlapping evidence generated throughout the development.
Don’t Cut Corners
Hurrying from research to development without an integrated product development plan is a risky move. Organizations must go through the planning process with the understanding that this will be a starting point only, and that the plan will adapt as the science evolves. More importantly, through upfront structured planning – even while acknowledging things will change – the company will avoid road bumps and move faster as it progresses toward commercialization. Developers of innovative therapies may be charting new waters, but with proper strategic planning, their horizons could be unlimited.
About the Author
Christian K Schneider, M.D. , is Head of Biopharma Excellence and Chief Medical Officer (Biopharma) at PharmaLex. He was previously interim Chief Scientific Officer at the UK’s MHRA, where he was also Director of the National Institute for Biological Standards and Control (NIBSC) for five years. He has also held leading positions at the Danish Medicines Agency and at the Paul-Ehrlich-Institut, Germany’s Federal Agency for Vaccines and Biomedicines.
At EMA, he has chaired the Committee for Advanced Therapies (CAT) as well as the Biosimilar Medicinal Products Working Party (BMWP), and served as a member of the Committee for Medicinal Products for Human Use (CHMP). He is one of the key architects of EMA’s advanced therapies and biosimilars framework. As a regulatory scientist, Christian has published 50+ articles in international, peer-reviewed journals. Christian [email protected], www.biopharma-excellence.com
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