Weighing Up the Value of Next-Gen Therapies

Despite the numerous challenges facing the development, manufacture, and commercialization of next-generation therapies, the end value proposition they offer is significant and worth the effort from stakeholders.

Next-generation therapies offer significant promise for patients; however, perseverance is required by industry stakeholders to overcome the hurdles associated with their development and manufacture. To find out more about the challenges facing the development, manufacture, and commercialization of next-generation therapies, as well as the utility of advanced technologies and criticality of CDMOs in driving innovation, The Pharma Navigator sat down with Miguel Forte, President, ISCT, board member of ARM and CEO of Kiji Therapeutics.

Many Associated Challenges

TPN: Could you give an overview of the specific challenges pertaining to the development and manufacture of next-generation therapies?

Forte: The challenges for the development, manufacture, and commercialization of next generation gene therapies are multiple. These challenges relate to science and technology, clinical evidence, manufacturing and scalability, regulation and access, and finally talent.

From the technological perspective we have seen enormous developments over the past few years and have enabling technologies for gene delivery and gene editing. Nevertheless, we need better delivery systems in terms of payload, targeting, and safety. Gene editing technologies have and are still progressing as we need further precision and capacity.

The generation of clinical evidence is a must, and we are progressing from small indications and orphan diseases to larger patient population needs. It is important to expand the generation of relevant clinical data supporting the eventual use of these products done in a focused and ethical way.

Manufacturing ability and scaling capacity still represents a challenge and is associated with relatively high costs. Developments in making the manufacture of gene therapies more affordable and with higher capacity is also a must to enable the translation of these products in therapeutic realities.

The regulatory environment has followed and evolved with the field, and we see strong partnering with developers in the assessment and support of the development of new generation therapies even if the element of access, namely reimbursement and payment for these products is still lagging behind the expectations.

Finally, it is important to be conscious of the need to have the right talent for the multiple translation steps in development of these therapies. From research to patient management, we need to focus on expanding the right expertise. Multiple organizations, including ISCT, have a focus on talent development to enable faster and better development of new products.

One aspect to point out is the innovative approach of enabling the targeting of single gene mutations based on a platform regulatory approach. Indeed, a critical success factor for this is to adapt the processes all along the value chain of translation to the specific realities of these products. Only by adapting in this way can we make these therapies available to patients in need in a timely manner.

Multiple Approaches Being Explored

TPN: What tools are helping to overcome these development and manufacturing challenges?

Forte: Two main aspects are critical in gene therapy; gene delivery and gene editing. The development of new gene delivery approaches is needed to deal with tissue specificity, dose management, payload capacity, and safety aspects. Multiple approaches are being explored and transformed in viable products with viral vector optimization. In addition, alternative means of gene delivery, line lipid nanoparticles, are also being delivered. The vision is to develop optimized approaches for different pathologies, conditions, and tissues; this will improve efficiency, cost and capacity, and safety!

Gene editing technologies that will enable precision editing are also being developed to address not only monogenic but also polygenic conditions.

Future Areas of Innovation

TPN: Are there any potential areas where further development is needed?

Forte: The areas at the forefront of innovation are cell sourcing in cell therapy, where the use of iPSCs [induced pluripotent stem cells] will represent a progressively alternative solution to donor-based approaches. Also opening the door to more allogeneic approaches and further cell gene edits for optimization of the cell-based therapy products.

For gene therapy the ability to do poli-gene edits and consider epigenetic approaches are still not reachable but will eventually possible.

One point to make is the fact that at this stage we are not in a position to do heritable gene editing approaches because the risk/benefit ratio is not favorable as there are alternatives for the therapeutic needs and we do not have the knowledge and control of the risk implications. This approach should be under moratorium for the foreseeable future.

Translating Knowledge and Experience

TPN: Why is flexibility particularly important for the increasingly complex development pipelines?

Forte: As the advanced therapies represent new development challenges, from the basic science to the clinical translation and regulatory discussions it is important that we all, with the right talent development, are prepared to consider also innovative approaches that require adaptability and flexibility. It is a matter of translating the knowledge and experience of other field to the scientific and innovation reality of these new therapies.

Worth the Commitment

TPN: How are CDMOs utilizing advanced technologies to drive forward innovation in next-gen therapies in your opinion?

Forte: CDMOs are critical partners in this process as they have the ability to cut across multiple approaches and be partners from early stages of product development. The process development part of their value proposition is key, particularly to early-stage start-ups that need a partner that helps channel the product development and has access to multiple innovative technological approaches.

Several companies are developing new technological solutions and approaches, equipment and processes, that will represent improvements that if implemented early in the product development path will increase the value proposition of the therapeutic solution from quality aspects to capacity, speed, and cost.

Overall, the next generation of therapies represent opportunities of long-term benefit and cures. The passion of that vision makes us engage in the innovative efforts of developing these products.

It is important to stress that because of all the challenges of these new technologies, needing new solutions and development options, we must be resilient and persevere towards the objective and rely on partners and stakeholders that enable the effort. In particular, it is key to have access to funding, be it non-dilutive grant type as well as equity risk based. It takes an entire ecosystem to be successful but the value opportunity for patients, and the business case associated, are significant and worth the commitment!

Photo by Elena Mozhvilo on Unsplash