State of Industry
After several decades of slow but steady progress, the commercialization of gene therapy has at last reached an inflection point. With now multiple modalities of gene therapy achieving regulatory approval in both the US and Europe, a growing body of pre-clinical and clinical experience suggests that there will be a sharp increase in new IND and BLA applications and approvals in and around the field. Given recent clinical successes, drug companies have shown significant investment in gene therapy technologies. However, given the prohibitive costs of vector development and subsequent regulatory approval, this investment has largely been limited to those indications for which sufficiently large patient populations exist to support a financially viable model of commercialization.
While legislative action has made some progress in stimulating investment in therapies for rare disease, today’s commercial R&D and governmental regulatory environments have yet to adapt to the unique needs and opportunities presented by gene therapy. Much dogma rooted in traditional small molecule pharmacology is still practiced. This dogma is at best unnecessary and expensive, and at worst is prohibitive to drug commercialization. There are many monogenic diseases that have robust pre-clinical proof-of-concept, but due to ultra-rare prevalence lack a viable commercial model under the current drug development paradigm.
In anticipation of FDA’s requirements for successful IND approval, companies may over compensate the amount of IND-enabling efficacy and safety testing performed, thus driving costs needlessly higher and causing lengthy delays in filing. Likewise, current clinical protocols for investigational gene therapies typically require dozens of patients to fulfill a typical Phase I/II + Phase III trial, a number that is simply unachievable for ultra-rare diseases wherein total patient populations approach the number of trial participants required. Ultra-rare disease, with prevalence often times less than 1000 people, needs to establish a new pre-clinical and clinical paradigm that is safe but recognizes the costs associated with bringing therapies for these diseases to clinical trials and eventual marketing approval. Rigid testing of many Platform Vectors Gene Therapy technologies (PVGT) have proven these delivery systems safe and effective. PVGT affords an opportunity to leverage the efforts of previous studies, allowing investigators the ability to cross-reference previous work which can save valuable time and money.
Under the current modality of preclinical and clinical testing, each company designs and pays for their own studies related to vector biodistribution, immunogenicity, shedding, etc. – possibly, but not always, cross referencing these studies for future filings. By cross referencing previous studies, the time and cost of the studies are largely ameliorated. However, these studies are generally kept proprietary. We believe PVGT is an excellent opportunity to realize economies of scale in pre-clinical and clinical vector development, especially regarding raw material manufacture and generalizable vector toxicity testing. In addition, PVGT may enable smaller, more efficient clinical trials, including a modality of combined phase I/II/III clinical trials utilizing as few as a dozen patients to achieve provisional marketing approval. However, there currently exists no defined path to enable this potentially transformative approach.
To advance PVGT, Odylia and its pre-competitive members work closely with the Center for Biologics Evaluation (CBER) within FDA, where Odylia serves as a single-center clearinghouse for PVGT-enabling data, physical materials, pre-contracted service providers, and knowhow related to advancing generalizable AAV therapies into and through clinical trials for specific indications. The resources within the platform are available on an a la carte basis to qualified Odylia members in good standing. By working together in a pre-competitive landscape, Odylia and its members are ushering in a new era of efficiencies and economy of scale in pre-clinical and clinical gene therapy vector development.
Need for Change
Novel approaches to developing strategies for IND applications and clinical trial design are necessary, especially for rare and ultra-rare diseases. By coming together to use Odylia’s status as a non-profit as a central sponsor, the ability to cross-reference studies, reuse of physical materials such plasmids and GMP grade vectors, and redefinition of lean clinical trial design, there are cost and time savings to be realized. Using Odylia as the sponsor, a platform delivery system could have one comprehensive study conducted to test toxicity and safety and hold a letter of cross-reference to make available that platform for use with other indications. In addition, by standardizing the manufacturing method used for AAV production within the Odylia network, a temple CMC section, including reduced burden for adventitious agent testing, may be developed for the use of all Odylia members which may be used whenever an Odylia AAV manufacturer is selected for GMP virus manufacture.
Using Odylia’s non-profit status there is opportunity to make both the pre-clinical and clinical regulatory process more efficient as the FDA may be more approachable with a smaller, non-profit entity. Holding letters of cross-reference, making and storing larger batches of platform vectors and plasmids, using Odylia’s network of discounted services and utilizing Odylia’s independent, non-profit status to make these available and collaborate with development companies are only a few of the opportunities to change the ability to bring rare and ultra-rare indications from the lab into the clinic.
By taking a cross-section of pre-competitive Odylia Members with the common goal of strategizing and developing a new protocol for rare and ultra-rare IND submissions and clinical trial design, there is opportunity to dramatically change the frequency and costs associated with bringing novel therapies to trial. Through working together in a pre-competitive landscape, Odylia members are defining where non-competitive synergies exist, providing value for all and helping advance the field as a whole.
Who’s Included
Odylia’s pre-competitive consortium is open to entities both directly and indirectly supporting the development of AAV therapies. We welcome members from the following spaces:
- Industry GMP manufacturers:
- Plasmid manufacturers
- For-profit viral manufacturers
- Non-profit/academic viral manufacturers
- Pre-clinical research CROs
- Drug development companies
- Regulatory experts
- Clinical CROs
- Clinical trial centers
- Patient advocacy groups
Acceptance to the consortium is at the discretion of the Executive Committee. Each participant will be asked to sign a CDA.
Goals
Kickoff will be a one-day symposium to be hosted by Odylia with a resource provided to document the process. Design of the kickoff meeting will be to:
- Have open dialog and detailed discussion on how best to produce standardized preclinical and clinical protocols
- Develop a timeline for completion of the suggested protocol
- Produce an outline for a suggested protocol with general agreement from each participant
- Full collaboration of members is expected
A document will be sent to each participant after the meeting for review and comments. A final document outlining suggestions, solutions and detailing the protocol will be provided to each participant at the end of the symposium.
Following the kickoff symposium, Odylia will monitor progress to meet the following goals within the agreed upon timeline:
- Finalize a novel protocol to streamline IND submissions for rare and ultra-rare disease that can be used to gain efficiencies to save money and time allowing more indications into the clinic
- Develop a standardized template CMC including reduced burden for external adventitious agent testing from product to product
- Finalize a novel clinical protocol and endpoints where appropriate to allow more rapid marketing approval of novel therapies
- Allow consortium members to continue to monitor progress of the protocol to use in their own advancement of products
- Make available any centrally developed products and studies via Odylia to the consortium to use
Future
While the initial consortium focuses on a small number of pre-competitive members, we recognize the need for global cooperation within the gene therapy space. Upon completion of the goals of the pre-competitive consortium, we propose it to additionally function as a precursor to a gene therapy trade association open to the broad array of entities who engage in activities directly or indirectly supporting human gene therapy. Members of the pre-competitive consortium will be invited to join the steering committee to form the trade association. This association will be formed to fulfill the following functions:
- A central representative body to put the views of human gene therapy companies to government departments and agencies
- A central body to engage with insurers and government agencies to determine best practices for reimbursement for gene therapy products
- Establish public good will toward human applications of gene therapy
- A research and statistical center, to aggregate and publish statistics, and to provide analysis on human gene therapy and other relevant market information
- A technical center providing commentary, guidance and advice on all legal and other regulatory developments of relevance to human gene therapy.
- A forum for the exchange of non-competitive information.
- Promote the human gene therapy industry
Non-competitive Consortium Value Proposition
The novel protocol will allow more targets to reach the clinic faster and much more economically.
- Participants will be given first rights to bid on services or share in IP when applicable
- If Odylia is sponsoring the trial, participating Members will be given preference on negotiating pricing and sharing in IP
- Direct exposure and collaboration to other consortium members will provide opportunity for Members to offer services, find and promote new products and learn more efficient ways to bring IND’s to market
- Streamlined path to INDs and BLAs will enable novel therapies to reach market faster and at lower costs than previously possible
- Membership in steering committee to launch a gene therapy trade association
For more information, please contact Consortium@odylia.org.