What are the global innovations in cell and gene therapy? What opportunities and challenges are emerging and can therapies get to market faster? DDW’s Megan Thomas finds out.
Bruce Levine, International Society for Cell & Gene Therapy (ISCT) Immediate Past President and Chair, Strategic Advisory Council, says a critical challenge that has become apparent for the CGT sector is the need for workforce development and training resources. He says: “In recent years, the field has seen exponential growth, which has outpaced the rate at which new professionals enter. This has created significant skill gaps which urgently need to be addressed to support the continued and sustained growth of the field. This issue has become a key focus for the ISCT, and we have been working to identify and develop initiatives to help alleviate these shortages.”
He continues: “ISCT has also embraced the opportunity to foster collaboration among the CGT community to enable successful process development and regulatory compliance. Many developers encounter multi-year delays in programme development because they fail to invest in the development of later stage processes critical to scale-up while collecting early clinical data. The regulatory burden with respect to both comparability and the expectations of process and analytical robustness is ever-increasing during development. The deeper the understanding of product and process from a characterisation standpoint, the smoother the regulatory conversations and development pathway will be.”
According to Stuart Curbishley, Chief Manufacturing and Development Officer at adthera bio and previous Head of Business and Project Development at the University of Birmingham’s Advanced Therapies Facility, the academic CDMO considers one of the most pressing challenges year-on-year to be the attraction, and retention, of the best talent in the CGT arena. He adds: “Allied to talent acquisition, the need for adaptable and sustainable training to equip the growing workforce in CGT will be central to our, and the wider sector’s, success.”
Curbishley explains that as the wave of new therapies in development continues to increase, global pressures on manufacturing availability will become more acute. Whilst this is a challenge for the sector, it presents opportunities for small centres like the university’s to attract new business and diversify its portfolio. Moreover, he says that global supply chain pressures will continue into 2023, combined with instability in the financial markets that will make cost of goods high on his watchlist of risks to manage. He says: “Whilst 2023 brings new and additional challenges, I remain positive that the outlook is exciting and anticipate a successful year for our centre and the CGT community.”
In 2023, Matthieu de Kalbermatten, CEO of CellProthera, looks forward to presenting the final safety and efficacy results of the company’s Phase II clinical trial, and for moving into Phase III. He says: “Significantly, there is a new scheme set up in France whereby innovative biotherapies that address unmet medical needs can enter the market following a successful Phase II clinical, while running a Phase III in parallel. This will give us the opportunity to open dialogues with the regulatory body and gain invaluable experience in the marketing of our CGT product.”
For the industry, especially in Europe, initiatives and government regulatory reforms represent a great opportunity for companies such as CellProthera to bring their therapies to patients more easily. De Kalbermatten says the accelerated regulatory pathways will be key to getting more CGTs to market, however, in order to make it to approval pathways, many start-ups and smaller biotechs need to secure investments. He says: “The investment landscape has been tough this year and that looks to be carrying over into 2023. However, there is solid hope that the situation should come back to normal by the end of 2023 according to the usual ‘up and down’ cycle in the industry.”
Industry at crossroads
According to Jason Foster, Chief Executive Officer and Executive Director of Ori Biotech, the CGT industry is at an important crossroads: “We have clinically proven cures for cancer and rare diseases that are unfortunately, all but inaccessible for patients. The first-generation CGT companies have failed to achieve market access and therefore have not generated the necessary return on the investment made in their programmes. Without commercial success soon, we fear that CGT might be relegated to the dustbin of history as an interesting science project that never really made it.”
The solution? According to Foster, the industry needs to work together to address the problems from the earliest phases of pre-clinical development. “Entering pivot trials with a low-throughput, high-cost, highly variable, paper-based process is no longer acceptable. Clinical endpoints are no longer the only things that matter. Manufacturability matters. Cost of goods (COGs) matter. Accessibility and affordability matter. Doing all the hard work to get a product approved that is too hard to make and too expensive to reach patients is no longer an acceptable outcome. The only endpoint that really matters is how many patients can be successfully treated (per year) with a therapy. If we use that as the measuring stick, we still have a long way to go.”
Vered Caplan, CEO of Orgenesis, shares that the company has spent 2020-2022 setting up its global point-of-care (POCare) platform/network. She believes that 2023 will be a banner year for decentralised processing as Orgenesis and its partners move projects into clinical trials all over the world. She says: “In 2023, CGT will continue its rapid growth, and several more candidates will be approved. However current processing methods (and associated cost) will continue hampering the global availability and accessibility of these life changing therapies. In addition to processing complexities and associated cost, recruiting/training the workforce will remains a significant issue.”
Caplan says that this is why Orgenesis has created an accredited Master’s Degree programme in the EU – both wet lab training in person and virtual/in-person classwork. She says: “To solve processing issues, many technology companies will continue working on the tools/equipment of the future but those solutions are still a long way away from approval for commercial use, so the field will need to look at shorter term solutions to address the disparity between demand and supply of CGTs globally.”
Lentiviral vectors demand
Naiara Tejados, Head of Marketing and Technology Development at VIVEbiotech & Natalia Elizalde, Chief Business Development Officer at VIVEbiotech, anticipate that 2023 will be a very good year for VIVEbiotech, due to the increasing demand for lentiviral vectors. They note that the gene therapy market in general, and the lentiviruses market by association, is growing enormously. However, ATMPs are highly personalised medicines whose productions often need to be tailored to each patient. While this often translates into longer delivery times, the initial dedication is well worth it.
Tejados and Elizalde believe that as with any other sector, in gene therapy there are also threats that must be closely watched. But given that viral vectors are today the most efficient vehicle for successfully delivering healthy genes to diseased cells, we believe 2023 will be a promising year for viral vector manufacturers.
CGT growth and interest
Head of Strategic Marketing & Commercial Development for CGT at Lonza, Fatma Senkesen has observed tremendous growth and interest in the CGT space in recent years. She says: “We anticipate this will continue because of the unmatched levels of efficacy demonstrated by many CGTs. The drive to get to the clinic and the market first will be even more pronounced, especially in areas such as rare diseases, where there are smaller patient populations.”
Senkesen sees several opportunities: “First, we see more products reaching commercialisation and expanding into new indications and regions. In cell therapy, immune cell-based therapies dominate the market and viral vectors experience substantial growth as they can be therapeutics on their own or support cell therapies as raw materials. Cost of goods management emerges as an important topic relating to productivity, scalability, and raw materials. Furthermore, providing the flexibility needed to ramp manufacturing up or down depending on demand cycles has become more critical.”
Steven Henck, Vice President of R&D at Integrated DNA Technologies, observes: “From the larger industry perspective, we see increased attention from regulatory agencies with newly released in vitro diagnostics (IVD) regulations in the EU as well as ‘draft guidance for industry’ provided for Human CGT, particularly CAR-T therapies, from the FDA. There is a challenge to balance the time required to provide an appropriate focus on safety with the opportunity to treat patients in critical need. Lending to the time-to-clinic discrepancy, we also see increasing demands on manufacturing capacity for CGT reagents.”
Henck considers there to be a shared challenge to provide efficient, end-to-end manufacturing solutions for targeted CGTs by methods that are well-tolerated, enabling delivery to patients.
Aaron Dulgar-Tulloch, Head of R&D, Cell Therapy at Cytiva, observes continued growth in the CGT industry, despite the impact of Covid-19. In order to this to be sustained, he says: “There is a strong clinical trial pipeline that will need automated and integrated manufacturing technologies for advanced clinical trials and commercial production. We also recognise the growing pipeline of allogeneic cell therapies entering development and early clinical trials and have initiated collaborations to ensure these therapies have strong manufacturing platforms as they progress.”
Dulgar-Tulloch sees continued growth in autologous cell therapy, with a variety of new indications progressing through clinical development. He says: “This includes indication expansion for on-market therapies as well as potential opportunities beyond haematological cancer with new technical advances. Allogeneic cell therapy is also starting to accelerate in early development programs. However, the field is still working through Covid’s impact on clinical trial recruitment, supply chains challenges, and decreased funding availability.”
After many years, Clive Glover, General Manager of Gene Therapy at Pall, is seeing the therapeutic and scientific benefits of gene therapies being recognised. Despite this progress, he says the industry is continuing to feel the after-effects of Covid. Looking to 2023, he says Pall will continue working to develop the integrated solutions and tools needed to accelerate the development of these novel therapeutics.
He observes: “Like many industries, the gene therapy market is impacted by global financial markets. However, the change in financial markets can also be an opportunity for us. Previously, when investments were easier to access, companies focused a lot on speed to market without fully developing their manufacturing processes. Now, when companies must be more strategic with funding, it gives them an opportunity to step back and think longer term about their manufacturing processes and commercialising their pipeline.”
Kathie Scheider, Director, Global Commercial Lead, Cell Therapy Technologies at Terumo Blood and Cell Technologies, says that in order to keep pace with the rapidly changing CGT market, collaboration is needed.
Scheider highlights that scaling CGT manufacturing processes continues to be an industry challenge: “This is amplified when transitioning from development to commercial GMP manufacturing. There is a need for platforms and tools that provide flexibility in scale: smaller scale for use in process development and larger scale for production. The smaller scale would ease time and cost of testing various parameters of a process and larger size would provide efficiencies of scale.”
Eye on Asia
“The world of CGTs is incredibly exciting with so many differing therapies in development, with many currently looking very promising in clinical trials,” says TrakCel CEO Fiona Withey. “This represents opportunity but also potential challenges. With each of these therapies comes different support partners and supply chain processes.”
Withey notes that Asia is a hotbed for CGT development and predicts there will be opportunities and initiatives in the future. For her, this brings a new level of complexity to the global supply chain with different regulatory requirements – partners and languages, she gives as an example. She says: “We will all eventually be connected across a global ecosystem that needs to be carefully managed and controlled to ensure that patients get access to the best possible treatment options.”
eXmoor, a technical and strategic consultancy, says that the biggest opportunity for the company in 2023 will be the launch of its CGT clinical GMP manufacturing facility in the UK. The company’s founder and CEO Angela Osborne said: “We are developing infrastructure and building out a team to directly deliver the manufacturing capabilities that we know the sector needs. Adding capability to capacity for CGT manufacturing is another of the sector’s biggest challenges.”
Some of the challenges Osborne identifies include the current lack of investment opportunities in the current economic landscape following a boom during the Covid pandemic into 2021, as well as the ongoing post-pandemic and post-Brexit disruption to global manufacturing supply chains.
DDW Volume 24 – Issue 1, Winter 2022/23 – Cell and Gene Therapy Guide