Five routes to market
for novel therapies

Next-generation therapies were headline news long before the arrival of SARS-CoV-2, the virus that causes COVID-19. But the successful development of COVID-19 vaccines, including mRNA vaccines, has thrown next-generation therapies into the spotlight and renewed the prospect of a boost to the advanced therapy medicinal products (ATMPs) sector.

Although ATMPs are very promising, exploiting the technology has been challenging. The marketing model for ATMPs is markedly different from conventional development paradigms, so organisations must adopt multidisciplinary strategies as early in development as possible.

Advanced therapy medicinal products (ATMPs), to use the EU and UK term, or cell and gene therapy products (CGTPs) as they are called in the US, are game changers for treating severe conditions that at present have no or 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 $21.2bn by 2028.

With this momentum, the pharmaceutical industry is facing a new era in patient treatment and disease prevention and management. The ATMP sector, currently considered to be at an adolescent stage by analysts, has great potential to make personalised medicine a reality and to improve global health through wider access to innovative medicines and devices.

Nevertheless, there are challenges as well as opportunities within the sector, particularly when it comes to commercialisation of products. Innovative therapies employ a model that differs considerably from conventional development paradigms – and one which requires a more tailored approach. At heart, the ‘traditional’ clinical development paradigm is often not applicable because ATMPs are dealing with smaller patient populations – they have special requirements for manufacturing where patients’ lives can depend on the speed in which a therapy can be made available and they offer pricing models that payers might see as prohibitive.

Companies need to do three things in order to plan for – and mitigate – the risks along the way:

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
3. Analyse the healthcare landscape to determine a market access model that appeals to decision-makers and payers.

With advanced therapies, there are many complexities to consider in the commercialisation process. The smaller and more targeted patient populations typical of this sector also have specific logistical requirements. For instance, 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 if shelf-life is very short.

Advanced therapies might be potentially transformative, but pricing for them may ultimately put off some payers. The underlying quality, regulatory and manufacturing guidelines that apply to traditional drug development must still be considered. Companies should therefore:

1. Undertake a risk/benefit assessment: Advanced therapies offer considerable benefits but they also come with risks, many of which are unique to this product class. Therefore, risk needs to be considered from an early stage, both for patients and for 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 its quality attributes, manufacturing process steps and therapeutic administration procedures.
2. Develop an Integrated Product Development Plan (IPDP): All development disciplines such as manufacturing, non-clinical 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 all be considered. The IPDP will be updated as development progresses, promoting organisational prioritisation and speeding up decision-making. Defining the patient population and the target stage for a given disease, for example, could have an impact on the design of non-clinical studies, etc.
3. Consider models to scale manufacturing: It can be a challenge to move a therapy from the lab to scaling it for supply to patients and producing a sterile drug product in sufficient quantities. To ensure scalability without needless expense, organisations need to align manufacturing readiness with the regulatory pathway, the patient population and the planned dosing regimen.
4. Accelerate commercialisation with an effective regulatory strategy: There are distinct aspects to the regulatory plan – all of which take place 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
   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 arrives regarding the competitive environment, study results, and interactions with regulatory agencies.
5. Initiate a market access strategy: For developers to gain market access, they have to be able to demonstrate clinical and economic evidence to providers, healthcare decision-makers and payers. Given the complexities of healthcare payment systems, it’s important to understand who will finance the therapy and how care will be reimbursed. Developers must consider strategies that offer a strong value proposition for decision-makers, ideally at proof-of-concept phase, so that later considerations on risk-benefit and cost-benefit converge.

Rushing from research to development without an integrated product development plan is risky. Organisations must go through the planning process with the understanding that this will just be a starting point and that the plan will adapt as the science evolves. More importantly, through upfront structured planning the company will avoid road bumps and move faster as it progresses toward commercialisation of the product.

Developers of innovative therapies face challenging and complex considerations. But with proper strategic planning, organisations can clear the obstacles that lie ahead and move closer to commercialising the novel – even curative – therapies that patients require.

Christian K. Schneider is head of Biopharma Excellence and Chief Medical Officer (Biopharma) at PharmaLex. Go to www.biopharma-excellence.com