The advanced therapy medicinal products (ATMPs) sector holds great promise. However, multidisciplinary strategies that begin early in the development process should be adopted, says Christian Schneider, head of Biopharma Excellence and Chief Medical Officer at PharmaLex. He outlines five strategies for avoiding pitfalls and boosting the success rates of development programmes.
SARS-CoV-2 and the successful development of Covid-19 vaccines, including mRNA vaccines, have thrown next-generation therapies into the spotlight. They have also given a boost to the long-term projections for the growth of the advanced therapy medicinal products (ATMPs) sector.
But although ATMPs hold promise, exploiting the technology has been challenging. Since their marketing model is different from conventional development paradigms, organisations need to adopt multidisciplinary strategies that begin early in the development process.
Novel therapies, known as ATMPs in the EU and the UK, or cell and gene therapy products (CGTPs) in the U.S., are game changers for treating severe conditions that have no appropriate therapies or limited treatment options. Driven by scientific innovations, impressive clinical outcomes, and a succession of new product approvals, analysts believe the market for advanced therapies is set to be worth almost $21.2 billion by 2028.1
Medicine is at a new threshold of how patients are treated and how disease can be prevented and managed. The ATMP sector offers potential in making personalised medicine a reality and improving global health through wider accessibility of innovative medicines.
However, that promise brings challenges. Innovative therapies employ a model that is different from conventional development paradigms — and one for which more tailored approaches are needed. One issue is that the ‘traditional’ clinical development paradigm is often not applicable to these organisations. 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.
To plan for – and mitigate –risks along the way, companies should:
- Plan early, building bridges between quality (CMC; chemistry, manufacturing and controls), non-clinical and clinical disciplines;
- Develop a regulatory strategy once drug development begins;
- Analyse the healthcare landscape to determine the market access model that will provide a strong value proposition for decision-makers and payers.
Importantly, organisations should initiate and consolidate interactions with regulatory authorities early on. Because ATMPs are complex biological entities, current regulations around them are complex and evolving. Sometimes, regulatory guidance can be too general for a developer to know how exactly to apply it to a given novel product. This is because regulators are unable to anticipate future developments when they draft guidance documents.
Regulatory agencies should be involved throughout a development programme so they stay in lockstep, and so organisations can incorporate their insights into the programme. Regulators are open to dialogue for immature and early programmes 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 minimises delays or risks of failure.
Five strategies to facilitate development
When it comes to novel therapies, there are many complexities to consider in the commercialisation process. Patient populations are often smaller and more targeted and even though that means product quantities can be low, they also have 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.
Pricing for advanced therapies may prove prohibitive for some payers. At the same time, the underlying quality, regulatory and manufacturing guidelines that apply to traditional drug development must be considered – and those guidelines can be nuanced, depending on country or region, which can make them challenging to navigate. Organisations need to:
- Undertake a risk/benefit assessment
These treatments come with risks, many of which are unique to this product class. Risk needs to be considered from an early stage – with a primary focus on safeguarding the patient but also minimising 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 programmes, commercial aspects such as targeting specific countries for commercialisation, the competitive environment and pricing /reimbursement aspects should be considered. The IPDP document will be updated as development progresses, promoting organisational prioritisation 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
Moving the therapy from the lab to scaling it for supply to patients can be challenging. To ensure scalability without burning cash, organisations must align manufacturing readiness with the regulatory pathway, the patient population and the dosing that is being pursued.
- Set up an effective regulatory strategy
There are distinct aspects to the regulatory plan – all happening in parallel – which should evolve as development progresses:
a. Documenting the goal, which can be visualised via the Target Product Profile (TPP);
b. Keeping pace with competitive therapies;
c. Maintaining regular checkpoints with regulatory agencies; and
d. 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.
- Instigate a market access strategy
To gain market access, developers must 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 holistic view of patient treatment and provide better real-world evidence, offering a stronger value proposition for decision-makers. This planning must begin 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.
Clearing the obstacles
Rushing from research to development without an integrated product development plan is dangerous. Organisations must go through the planning process understanding that this will be a starting point and that the plan will adapt as the science evolves. Through upfront structured planning – even acknowledging that things will change – the company will avoid road bumps and move faster towards commercialisation.
Navigating these concepts can be challenging but with strategic planning, organisations can move closer to bringing groundbreaking, curative therapies to vulnerable populations.
Volume 23, Issue 1 – Winter 2021/22
About the author
Christian K Schneider, MD, 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.
References
1. Advanced Therapy Medicinal Products Market Worth $21.2 Billion By 2028: Grand View Research, Inc, May 2021: https://www.grandviewresearch.com/press-release/global-advanced-therapy-medicinal-products-market
2,3. Next-generation therapeutics thrust into the spotlight, biopharma dealmakers, September 2021: https://www.nature.com/articles/d43747-021-00105-y
