One such promising novel modality for treatment is the use of oncolytic virotherapy. However, as with all new therapy advances, there are many challenges to be addressed to ensure that oncolytic viruses (OVs) are successfully brought to market. With such innovation accelerating across the globe, Kai Lipinski, CSO at Vibalogics, explains how these challenges can be overcome.
With approximately 10 million deaths reported every year, cancer remains a leading cause of worldwide mortality and is a significant healthcare burden.1
The global OV market is projected to reach $962 million by 2030 at a compound annual growth rate (CAGR) of 26.28% during the forecast period from 2020 to 2030.2
With this in mind, it is clear that novel treatments are desperately needed to improve patient outcomes as well as relieve the financial burden and impact on healthcare system resources.
Alongside other traditional cancer therapies, OVs have the potential to greatly enhance the effectiveness of existing therapies and create new ones within the oncology space.
Oncolytic virotherapy is a form of immunotherapy that directs viruses to infect and destroy cancer cells, thereby activating the patient’s immune system to recognise the cancer cells as “foreign tissue.”
Many viruses are inherently oncolytic, which means they can replicate and destroy cancer cells while sparing normal, healthy cells. With many sophisticated molecular biology tools available, viral genomes can be bioengineered by researchers to direct and enhance their cytotoxicity towards specific cells, such as those present in tumours.
There are several examples of diverse OVs already in development that use a vast array of naturally occurring or genetically designed forms of common viruses as a platform.
These include HSV, adenovirus, vaccinia virus, Newcastle disease virus, poliovirus or reovirus. Thanks to steadily increasing virology knowledge, the number of new, innovative oncolytic virus platforms is continuously expanding, with a number of recent additions, such as vesicular stomatitis virus (VSV) and arenaviruses.
The OV market is rapidly growing as these products increasingly pass from trials into development, with up to 200 companies now working within this space.
Forecasts predict that the global market for OVs is set to hit $24 million by 2026, showing a compound annual growth rate of 6.8% for the next 5 years.3
From SMEs to Big Pharma, there is now a need for solutions to overcome barriers to development and streamline OV production. As with all emerging products, the journey to commercialisation comes with many challenges. But what are these obstacles and how can they be successfully overcome?
The challenges
From diverse viral immune responses, OV development and production to analytical and stability issues and regulatory approval hurdles, OVs present a number of challenges.
Creating the panacea OV: Although OVs hold great promise, developing an OV that meets all or at least many of the criteria needed for broad spectrum oncology treatment is extremely difficult.
There are many virus platforms available and each one offers unique advantages for therapy, as well as its own distinctive pitfalls. Every type of cancer cell also has a unique profile. Therefore, finding a single OV that exhibits broad spectrum infectivity of cancer cells is extremely challenging.
Alongside the mechanism of action, the overall immune responses to OV infection can differ between patients. Not every patient’s immune system will not mount an effective immune response against the cancer cell.
Some may have pre-existing immunity to OVs, such as those using influenza virus or measles virus as a vector.
Lack of dedicated resources: There is also a lack of development, scale-up and commercialisation resources available to OV developers. As all viruses behave differently, expertise is needed to comprehend their optimal manipulation and development.
Manufacturing experience and capacity, as well as advanced equipment and operational excellence is then required for their effective production. Not only that, viruses exhibit novel production and product stability issues that need innovative solutions.
For example, transporting and storing such products can be challenging because of cold chain requirements.
Difficulties with clinical trials: In addition to all of this, clinical trials pose a significant hurdle. Owing to the novelty of this modality, there are many aspects of OV trial development that require optimisation.
From the search for the optimal viral delivery platform, vector design and therapeutic gene selection to patient selection and biomarker analysis, trials require additional expertise.
Solutions for OV market entry
So how can these challenges be overcome? Developers are focusing their resources on the research and development (R&D) of promising viral platforms and the optimisation of development methods and processes.
These include developing methods to select the best virus candidates and cell-line for viral production. Regarding OV and manufacturing platform selection, there are some key considerations that can help to improve the process.
OV platform selection: When selecting an OV platform, making proper use of the strengths and weaknesses of platforms already in clinical trials or optimised for development can help to streamline the development process and simplify regulatory approvals.
Manufacturing platform: Making use of already established virotherapy processes is a crucial step to creating a manufacturing platform for your selected OV candidate.
Partnering with a contract development and manufacturing organisation (CDMO) that specialises in virotherapy can really help. They have the subject matter experts and established manufacturing platforms into which you can plug your new OV candidate.
A CDMO’s expertise in preapproved cell lines to optimise seed material is critical for speed to commercialisation. As is experience scaling-up from clinical to commercial quantities.
Specialised infrastructure and personnel can drive the development of streamlined processes and quality analysis procedures. Creating this in-house can be a drain on resources; by contrast, a CDMO could provide immediate access, drastically reducing development timelines and initial investment costs.
Finally, the industry is moving away from scale-limiting and labour-intensive traditional scale-out manufacturing processes (T-flasks, cell stacks, roller bottles) towards scalable, suspension-based, single-use bioreactor platforms and also working toward closed systems operation to minimise contamination risks.
This is increasing process control, reducing batch variability, facilitating cGMP-compliant production and ensuring the financial viability of commercialisation.
A true partnership to fight cancer
Now is a crucial time for cancer patients throughout the world as new treatments move from development to manufacture and commercialisation. Working alongside expert partners with GMP capabilities and commercialisation expertise will accelerate this innovation to market.
References
- www.who.int/news-room/fact-sheets/detail/cancer.
- www.prnewswire.com/news-releases/global-962-million-oncolytic-virus-therapies-market-to-2030-301276790.html.
- www.marketwatch.com/press-release/global-oncolytic-virus-therapy-market-size-2021-2025-with-top-countries-data-key-leaders-analysis-segmentation-growth-future-trends-gross-margin-demands-emerging-technology-by-regional-forecast-2021-04-19.
