Specialist
Director at a biomedical research organisation and medical school
Agenda
- Notable driving trends and developments within gene therapy, including overall industry growth-inducing factors
- Overview of clinical risks and uncertainties associated with gene therapy delivery, highlighting a field emphasis on risk mitigation and unwanted immune responses associated with viral vs non-viral delivery methods
- Innovation and technological advancement in gene therapy delivery, highlighting higher-quality improved capsids
- Therapeutic outlook and best-suited delivery methods for indications across CNS (central nervous system), oncology and cardiovascular disease
- 2023 industry outlook and future potential
Questions
1.
What developments and trends have taken place in the gene therapy industry that you believe are particularly noteworthy?
2.
How have you been assessing the uptake of AAV [adeno-associated virus] gene therapy methods, which you mentioned are approved and marketed? How have they disrupted the historical paradigms in these disease indications? Have we seen that shift in the industry towards using these therapies more so in the first line compared to other treatment options?
3.
Traditional pharmacology, such as the use of small molecules, has been proven to have its advantages, but there are disease cases where they’ve proven to be ineffective, prone to unwanted side effects, and overall not an effective approach due to the pathology of a specific disease. As we’ve discussed, and as a result, the industry has witnessed an innovative shift towards the use of more gene therapy- and gene editing-based approaches. Can you just further elaborate on the mechanistic advantages of new and emerging therapeutic tools and approaches that have the potential to treat disorders for which small molecules have either failed or cannot be developed to treat, focusing on the disruptive effects of approaches involving gene transfer, such as gene therapy and genome editing?
4.
Although there’s a lot of excitement around the therapeutic potential, as you’ve outlined, around gene therapy and the clinical advancements that have been made already within the industry, such as Vertex and Crispr Therapeutics’ even near-term completion of an FDA submission of Exa-cel [exagamglogene autotemcel], which is more on the gene editing-based side, there are still clinical unknowns around gene therapy and gene editing. Could you outline the clinical risks and overall uncertainties that remain and that can hinder the adaption and overall utilisation of the two approaches?
5.
What risk mitigation strategies can be deployed, or have we seen be deployed by companies during the developmental stages to offset potential risks such as unwanted effects, toxicity concerns and off-target effects?
6.
Can you expand on risk mitigation efforts and advancements that have been made regarding retroviral integration for gene therapies?
7.
In January 2023, Pfizer reported its intent to trim early-stage research in rare diseases and is seeking to externalise development by licensing out programmes, including viral vector gene therapies. How are you viewing the company’s strategy to out-license to maximise success with its potential medicines? As we’ve discussed, it’s a theme in the industry to minimise risks, given the highly innovative and niche programme it has in development with regards to gene therapy.
8.
Are there any risks associated with outsourcing vs insourcing development?
9.
Is this out-licensing approach something that we see a lot of within the industry? Do we see more companies in-license vs out-license, or vice versa?
10.
How does the complexity of the manufacturing process impact costs, scalability and the overall timeline of gene therapy development?
11.
How does the need to personalise and customise gene therapies impact their manufacturing?
12.
We talked about the cost aspect of manufacturing gene therapies. How does the need for long-term stability and storage of gene therapies play into cost but also impact the manufacturing process?
13.
You mentioned that gene therapy delivery systems can be classified into viral vector-based and non-viral vector-based, including chemical and physical and also vaccination. Could you outline key points of differentiation of clinical applicability potential between viral and non-viral vector-based delivery systems, including factors such as efficiency and efficacy and any others that you feel are important?
14.
How does the risk of unwanted immune responses vary between viral and non-viral gene therapy delivery methods? You just pointed out there is more of an immune response with the viral methods.
15.
How should we be viewing the varying gene delivery systems on their flexibility and versatility for different disease indications and target tissues? How does the delivery method impact the specificity of gene therapy delivery for various disease indications?
16.
Could you highlight specific therapeutic indications that are best-suited for a specific delivery system?
17.
We’ve discussed the handful of AAV-approved gene therapies already on the market. Most notably, in 2022, Bluebird Bio, a major player in the segment, won FDA approvals for two gene therapies and will soon seek regulatory endorsement for a third. What is the current state of insurance coverage and reimbursement considerations for gene therapy?
18.
As previously noted, Vertex and Crispr Therapeutics Therapeutics started submissions of Exa-cel in sickle cell disease and beta thalassaemia in November 2022. If approved, it would be the first gene-edited-based gene therapy approved. How should companies go about managing correlated risks associated with potential commercialisation failures of gene-edited- and gene therapy-based approaches?
19.
What’s your risk-benefit analysis for the use of gene therapy?
20.
How is the state of competition in the development of gene therapies expected to evolve in the coming years and into the future?
21.
Is there a specific disease indication where there is not a lot of presence in development of gene therapies, which you believe will really benefit from a gene therapy to treat patients?
22.
Is there anything we haven’t discussed around gene therapies that you believe should be highlighted further or that is particularly noteworthy?
23.
Can you pinpoint 2-3 aspects from our Interview that are most important for our audience to take away and be aware of going forwards, with respect to gene therapy?
