Demonstrating the value of gene therapy in rare disease

Written by Charlotte Richards, Customer Strategy Director, OPEN Health Evidence and Access on Tuesday 17th August 2021

*This article was first published in Rare Revolution Magazine, Issue no. 013, Autumn, 2019.

Since the introduction of the gene therapy concept in the 1960s, significant advances have been made to bring this potentially life- hanging treatment approach to market; however, the introduction into clinical practice has not been without its challenges. Here we discuss these challenges, and potential strategies to over come them.

The life science industry has been investing heavily to accelerate advanced therapy medicinal product (ATMP) development and provide renewed hope to patients with rare and life-threatening conditions. Thanks to continuous scientific advancements and an increased understanding of targeted delivery, there is now a better understanding of how genes and cells can be effectively extracted, manipulated and delivered to patients in order to change the course of certain conditions. The vision that some rare diseases will be cured appears to be within reach. 

I bet you are thinking "well, that all sounds very positive", and you would be right. However, organisations planning to commercialise an ATMP will need to consider their route to market very carefully to ensure that their therapy is made available to the maximum number of patients who will benefit most. To achieve this, a number of factors need to be considered. In this article, we discuss the importance of demonstrating the value of ATMPs across the spectrum of stakeholders.

The value chain
The roadmap to launching a specialist medicine is relatively well defined. Implementation of tried-and tested launch frameworks supports a standardised yet customisable approach; reimbursement pathways and timelines are well understood; and there are widely reported parameters that support understanding of what constitutes a successful launch. However, the same cannot be said of ATMPs – there is no one-size-fits-all approach and the route to market is multifaceted

1. The manufacturing process and supply chain are complex
At present, there are few standardised processes that support timely and cost-efficient manufacture of ATMPs. Given the small target patient populations of current ATMPs, economies of scale are not an option. A centralised manufacturing approach is often taken, resulting in unfamiliar quality control and logistical considerations. The consequence of these factors alone includes a long lead time, high cost of goods and, ultimately, a high acquisition price.

2. The reimbursement pathway is not well defined

Given the high acquisition price, life science organisations need to develop innovative pricing strategies to support patient access to treatment. The clinical, patient and societal value of treatment needs to be demonstrated to all stakeholders and cross-border reimbursement strategies may need to be considered in some instances.

3. The burden of treatment needs to be considered 

Patients and their parents and carers need to be educated to fully understand what the preparation and administration process will involve, the common adverse effects post administration and the need for long-term monitoring to ensure continued effectiveness. In addition, they may be required to travel long distances to access treatment, stay away from home for prolonged periods of time to facilitate pre-treatment preparation and comply with peri-administration monitoring requirements.

4. Long-term efficacy and safety are unknown

Strategies to collect long-term outcomes data are critical to demonstrate sustained efficacy and a tolerable long-term safety profile, with regulatory authorities requiring 13–15 year patient follow-up data to assess long-term safety in some instances. Innovative approaches to data collection and stakeholder engagement will need to be considered to drive confidence in therapy, demonstrate long-term value and prevent loss to follow-up.

Putting plans in place to overcome all these challenges may be daunting and result in internalisation of teams during critical planning phases. Consequently, development and evolution of a value story that resonates across core stakeholder groups, clearly articulating the clinical and cost rationale for treatment and readying the market for implementation, may not be given due consideration.

Not adequately demonstrating and communicating value could delay market access, restrict the target patient population and result in low demand. At OPEN Health, we understand the importance of building a strategy that is underpinned by the needs of stakeholders across the value chain, and fuse value demonstration and communication in order to build a cohesive communications platform that drives a unified message through all stakeholder groups.

Demonstrating value to patients

The passive patient is becoming a thing of the past; now, more than ever, patients are the navigator of their own destiny when it comes to decisions regarding their treatment and healthcare. This is especially true for patients with a rare disease who, along with their parents and carers, must become the expert in their condition to ensure that they receive the right care that is aligned to their individual needs. Patient advocacy groups are hugely influential in this area, and their activity has been a key driver of health technology appraisal decisions in the past.

The introduction of gene and cell therapies is seen as a lifeline to some – a chance for a better future. Those with a rare disease, as well as their parents and carers, are keen to understand the good, the bad and the ugly to support them in deciding whether pursuing ATMP treatment is the right approach for them. Life science companies need to engage with patient advocacy groups early in the development journey to identify meaningful patient-centric clinical trial endpoints, build the narrative around immediate and long-term treatment considerations, and develop an appropriate patient support programme that openly discusses the complexities of ATMP treatment and provides materials to support patients to overcome the likely challenges in their treatment journey.

Demonstrating value to payors
With significant price tags, life science companies are under pressure to develop innovative pricing strategies that share the risk of treatment inefficacy. This risk needs to be balanced against the potential long-term benefit of treatment with an ATMP. Many national reimbursement systems implement a one-size-fits-all approach to assessing value, the parameters of which may prevent accurate representation of the burden of disease and impact on quality of life. These factors should be acknowledged during value assessments where there is a high medical unmet need and high levels of healthcare utilisation, both of which may be reduced by effective therapy. Life science companies need to find ways to demonstrate and quantify the value of ATMP treatment to the healthcare system over the long-term, and engage with payors to find ways to incorporate these into the value dossier and co-create appropriate pricing and value-based outcome models. Evidence generation strategies should be considered and carefully crafted with the end goal of ensuring access to the maximum number of patients who would benefit most.

Demonstrating value to clinicians
The efficacy of ATMPs continues to be the core driver of value for clinicians. When ATMPs demonstrate incremental benefit over current standard of care, as opposed to overall cure, clinicians will balance efficacy with safety and, importantly, the complex treatment process commonly associated with ATMPs. This may restrict the use of ATMPs to specific patient types in the minds of clinicians, which accentuates the need for a great first-use experience. With small patient populations currently the target for ATMPs, there is a core communication challenge for organisations trying to implement targeted educational campaigns aimed at clinicians most likely to be involved in patient selection for treatment. With an average of 7.3 physicians seen over the diagnostic period, it is critical that life science organisations fully understand the diagnostic and referral pathway to develop relevant targeted communication strategies. These strategies should aim to increase awareness of the symptoms of specific rare diseases, support patient identification through implementation of appropriate initiatives and enhance understanding of the potential value of ATMP treatment. In addition, there needs to be a dedicated support package for clinicians within centres implementing ATMP treatment strategies, ensuring clear communication of the complex processes involved in ATMP preparations and administration, supporting an evolution of the service model required to deliver ATMP treatment and developing a process for ongoing monitoring and assessment of long-term efficacy.

OPEN Health: supporting companies commercialising an ATMP

It is well documented that bringing an ATMP asset to market is no easy task, and there is little advantage in making an ATMP available if the patients who can benefit the most are unable to access it. At OPEN Health, we bring together expertise from across evidence generation, market access, healthcare professional communications and patient engagement to support companies commercialising an ATMP in navigating the route to market and create meaningful value strategies that consider the needs of all core stakeholder groups in order to facilitate successful market entry and ongoing uptake.

With broad expertise in bringing therapies to the people who need them our rare disease capabilities cover the full lifecycle. From improving diagnostic and treatment pathways, to impactful scientific and value communications through to innovative patient support and outcomes monitoring.


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