Reflecting on the World Orphan Drug Congress USA 2022 – Accelerating Patient Access: How Much Faster Should We Go?

This year’s World Orphan Drug Congress (WODC) USA annual meeting took place in Boston, where I was delighted to be joined by my colleagues Sarah Neubert and Cameron Costello from our growing USA office. I often attend the European WODC, but this was my first time at the USA meeting. As expected, there was a clear increased focus on pushing the pace of drug development and access. Innovation in real-world data (RWD) and gene therapies was inspiring to see, however, further work is needed to demonstrate the practical utility of these approaches, particularly beyond the USA setting. Furthermore, we have a continued responsibility to ensure that a focus on “speed” does not come at the expense of high-quality evidence and well-informed decision-making. ?

Maximising the Potential of Real-World Evidence

In line with discussions at ISPOR International earlier this year, WODC USA 2022 picked up on the theme of RWE and its use in regulatory and reimbursement decisions. Specifically, how RWE can reduce the burden of data collection on patients and how innovative data analysis platforms and methodologies can accelerate the generation of evidence that is needed for regulatory decisions was discussed.

Over the course of the conference, we heard from multiple companies who are developing collaborative data sharing platforms. These platforms aim to reduce the need for patients to repeat burdensome and sometimes invasive data collection activities, and maximise the impact and value of the data these patients provide. Jason Colquitt, Founder and CEO of Across Healthcare, passionately described his data platform that allows different researchers to access and share data from rare disease patient populations who have consented to their data being used on the platform. He also emphasised that platforms like his enable the sharing of analysis results with patients who have contributed their data through plain language summaries. This would be one way to indirectly encourage patients to continue contributing data, which organically increases the amount of RWD available.

Using innovative data analysis methods such as artificial intelligence (AI) and novel biomarkers was presented numerous times as a tool to increase rare disease patient sample sizes. Additionally, novel efficacy biomarkers that could be analysed earlier in the data collection process was discussed. Both topics were presented as opportunities to use RWD as additional sources of evidence to demonstrate safety and efficacy in regulatory submissions. Multiple AI companies spoke of their ability to identify additional patients from electronic medical records as a way to increase clinical trial and cohort study sample sizes. Contrary to these presentations, other attendees reported that their attempts at using AI to identify additional rare disease patients has yet to be successful. While the ability of AI to identify additional patients seems feasible, the mixed opinions in the community left us feeling that these methodologies will still need validation (e.g. by reviewing patient charts by hand) for the foreseeable future.

Another common topic throughout the conference was the idea of “de-risking” how investors see orphan drugs through increased sources of evidence. Emil Kakkis, Founder, President and CEO of Ultragenyx, spoke to the use of primary “disease activity biomarkers” in both the clinical trial and RWE setting to generate efficacy evidence earlier in the development pipeline. He argued that these markers are just one way that we could take calculated efficacy assessment risks to accelerate orphan drug development. That being said, he also emphasised the critical importance of preserving safety standards and developing these data with a high-quality clinical programme. While inspiring examples from phenylketonuria (PKU) and mucopolysaccharidosis (MPS) were presented, we share the concerns which were raised by payers about the suitability of these endpoints as evidence for meaningful patient outcomes upon which long-term decisions can be made.

At the Frontier of Next-Generation Therapies

Questions around next-generation cell and gene therapies centred around ways the rare disease community can ensure patient access to these revolutionary therapies promptly, while upholding clinical and safety standards. One overarching theme was streamlining and standardising across the thousands of gene therapy products and trials in development. Each product is treated as a unique therapy, manufactured at different sites and through different methods, and is held to different standards in different markets across the globe. The keynote panel focused on advancing cell and gene therapies for rare disease patients in the pre-commercialisation stage, calling for standardisation of international guidelines and even proposing creating global standards that are specific to small, rare disease populations. Philip Brooks, acting director from the Bespoke Gene Therapy Consortium, also advocated for the development of unified guidelines and practices for gene therapy development in the USA and described their initiative to incentivise companies developing platforms of products rather than singular therapies. It was clear, however, that from the payer perspective there are not enough gene therapy products in the market to warrant a fundamental change to long-standing reimbursement systems. While there may not be power in numbers yet, it is clear there is power in unification. Such streamlined approaches could allow companies to not only lower costs, but speed up access through formalised processes.

Uncertainty around long-term efficacy and safety of next-generation therapies is also limiting approval, reimbursement, and in effect prompt access for rare disease patients. Understandably, regulators and payers want to evaluate long-term data before approving and reimbursing these novel, high-cost therapies. Several attendees stressed the importance of selecting informative, measurable and clinically meaningful endpoints in order to demonstrate efficacy when long-term data are not available. Francis Pang, Senior VP of Global Market Access and New Market Expansion at Orchard Therapeutics, pointed out that these endpoints are not only crucial for demonstrating efficacy in a clinical trial setting, but can also serve as the successful basis for alternative payment models. Although there was support for innovation when it comes to efficacy measures, it was reassuringly clear that the same flexibility does not apply to safety.

Looking ahead to the coming years, the rare disease community will continue to be at the forefront of innovation, driving fundamental change and increased access to revolutionary next-generation therapies. By pushing for a streamlined approach to manufacturing and regulation, and innovating methods for efficacy assessments, rare disease stakeholders hope to create opportunities to promptly bring gene therapies to market in disease areas that were once not considered commercially viable. Currently, the concerns around safety and long-term efficacy are limiting the speed of this access. While the community is in agreement that patient safety should not be compromised in order to speed-up access, reimbursement systems may be willing to accept greater uncertainty with respect to long-term efficacy in order to accelerate access and make gene therapies a less risky investment.

Annabel, Sarah and Cameron are employees at Costello Medical, who provides scientific support to the healthcare industry in the analysis, interpretation and communication of clinical and health economic data. Due to growing demand across an increasing range of service offerings and geographies, Costello Medical has grown organically since its foundation in 2008 to a team of over 350 based in Cambridge, London, Manchester, Bristol, Boston, Singapore and Shanghai. Alongside our evolving technical and creative capabilities, we remain committed to our core values of high-quality scientific work coupled with exceptional customer service at competitive and transparent prices. For more information on our services, please visit our?website. If you would like any further information on the themes presented above, please do not hesitate to contact?Annabel, Sarah or Cameron.