Next-generation therapies were already making headlines long before we heard anything about SARS-CoV-2, the virus that causes COVID-19. The successful development of COVID-19 vaccines, including mRNA vaccines, has thrown next-generation therapies into the spotlight with renewed promise that is giving a boost to the long-term projections for the growth of the advanced therapy medicinal products (ATMPs) sector.
While ATMPs hold great promise, the path to exploiting the technology has been challenging. With a model that is markedly different from conventional development paradigms, organizations must adopt multidisciplinary strategies that begin as early in development as possible.
Christian K. Schneider outlines the five strategies that must be considered to increase the success rates of development programs, while avoiding some of the common pitfalls.
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 United States, have long been considered game changers for the treatment of severe conditions that today have no appropriate therapies or very limited treatment options. Driven by scientific innovations, impressive clinical outcomes, and a succession of new product approvals, the market for advanced therapies is projected to be worth almost $21.2 billion by 2028.1
With this momentum, we stand at the threshold of a new era in how patients are treated and how disease and illness can be prevented and managed. The ATMP sector is now considered at an “adolescent stage” by many analysts, also holding great promise in making personalized medicine a reality, and improving global health through wider accessibility of innovative and personalized medicines and devices.
With promise, however, come challenges. Innovative therapies employ a model that is markedly different from conventional development paradigms — and one for which more tailored approaches are needed. At the core, the “traditional” clinical development paradigm is very often simply not applicable to these organizations. That’s because ATMPs are dealing with smaller patient populations; special requirements for manufacturing where patients’ lives can depend on the speed in which a therapy can move from bedside to manufacturing and back again; and pricing models that can make the therapy prohibitive for many payers.
In order to plan for – and mitigate – the risks along the way companies should 1) plan early, building bridges between quality (CMC; chemistry, manufacturing and controls), non-clinical and clinicaldisciplines; 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.
Perhaps most important, organizations should initiate and consolidate interactions with regulatory authorities from early on. Initiate discussions with regulators early in development planning. Because ATMPs are complex biological entities, current regulations around them are also omplex — and constantly evolving. Sometimes, regulatory scientific guidance can be too general in certain aspects, for a developer to know how exactly to apply it to a given novel product. This is because, inherently in this field, regulators are unable to anticipate future developments when they draft their guidance documents.
Regulatory agencies should be involved throughout a development program so they stay in lockstep, and so that organizations can incorporate their insights into the program. Regulators are increasingly open to dialogue for immature and early programs, and they see their roles as enablers in addition to their more traditional roles as gatekeepers.
Ultimately, the goal is to build an agile approach to planning that minimizes delays or risks of failure.
Strategies are rooted in proper planning that starts on Day One and is designed to build bridges between quality, non-clinical and clinical disciplines.
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: Certainly these treatments 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 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 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: 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.
Rushing from research to development without an integrated product development plan is a dangerous proposition. 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 are charting new waters, therefore navigating these complex considerations can be challenging. But with proper strategic planning, organizations can clear the obstacles that lie ahead and move us closer to bringing ground-breaking, curative therapies to people in need.
1. Advanced Therapy Medicinal Products Market Worth $21.2 Billion By 2028: Grand View Research, Inc, May 2021.