Virotherapy platforms are increasingly being used in the development of novel and transformative therapeutics, offering the potential to drastically change the lives of patients. From gene therapies to vaccines, and oncolytic virotherapies (OVs), the biopharmaceutical industry has grasped the vast potential of virus-based drug modalities.
With growing numbers of virotherapies in the development pipeline, the pressure to deliver new drugs to critical milestones on the journey to market is rising. Demands for accelerating timelines to investigational new drug (IND) application in particular stem from a desire for critical medicines to reach patients faster and a drive for return of investment (ROI).
However, developing and manufacturing these emerging and often complex technologies is a considerable challenge. Successfully bringing new virotherapies to phase I clinical trial and beyond requires specialist expertise to overcome.
Here, we cover the trends driving the intense desire for accelerated time to IND in the growing market and highlights ways in which these pressures can be eased with the right support.
An urgent need for alternative cancer treatments
Cancer was estimated to have caused approximately one in six deaths in 2020 alone, highlighting the urgency for continued improvements in current treatment methods .
Although traditional cancer therapies have successfully improved survival rates, all of these have drawbacks. Being inherently invasive, surgery can pose its own risk to the patient, potentially resulting in post-surgical complications and chronic pain. Chemotherapy is often associated with harmful side effects that can be disabling in the short term. Radiation therapy can cause damage to healthy tissue surrounding the target tumor.
Immunotherapy approaches, including immune checkpoint blockade (ICB) and chimeric antigen receptor T cell (CAR-T) therapies, have demonstrated promising results. However, the heterogeneity of cancer, challenges in tumor cell targeting, and the immunosuppressive tumor microenvironment (TME) limit the consistency and effectiveness of these treatments alone.
New promise with advanced treatments
With the ability to specifically target and infect cancer cells, OVs promote the expression of genetic markers that trigger an immune response to these cells. OVs are therefore an ideal combination option with immunotherapies, as well as other traditional therapies, offering the ability to target a wider range of tumors and promote therapeutic efficacy .
The biopharmaceutical industry is continuously looking to develop OV technologies to improve treatment outcomes. Although only four OVs have been approved currently, there are over 100 in the development pipeline . Reflecting the potential of these therapies, the global OV market is predicted to grow at a compound annual growth rate (CAGR) of 26.2% between 2021 and 2028, reaching a value of $609.7 million .
Trending pressures for faster pathways to IND application
Offering the possibility to dramatically improve the lives of cancer patients and reduce mortality, progressing new OV products through the development pipeline quickly is largely driven by the need to provide urgent care. However, there are also several other pressures the biopharma industry is witnessing that are fueling this need:
- A desire to gain a market share
In a fast-growing therapeutic area with many competitors in the pipeline, it is becoming developers must act rapidly to deliver their molecule to market within unprecedented timelines to ensure a market share.
- Pressure from investors for return of investment (ROI)
Investors providing seed funding to develop new therapeutics will often outline key milestones they require the project to reach in a certain timeframe. If this cannot be guaranteed, there is the chance that there will be no further support with additional capital.
Although accelerating timelines may seem like a simple solution to meet these demands, the complexity involved in the development of OVs and reaching the IND application stage will naturally lead to various challenges.
Obstacles to speed on the road to IND application
Successfully transitioning OVs from the pre-clinical stage to phase I trials and beyond necessitates a proactive approach to decision making, looking ahead to understand the difficulties that could arise as the project progresses. This is highlighted by the need for developers to provide the proposed manufacturing methods and processes in IND applications to begin phase I clinical trials.
For OV projects, there are a number of difficult decisions that must be made in these early stages that could ultimately impact the potential for commercial success, including:
- Choosing between suspension and adherent cell lines
- Determining whether cell lines will be adapted to serum-free conditions
- Understanding the regulatory impact of using animal-derived raw materials in upstream processing
- Considering Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) regulations surrounding cell cultures derived from protected animals
- Conducting pre-GMP feasibility studies
- Proving genetic stability
- Determining the virus recovery and virus purification strategies
These decisions will ultimately impact all further downstream stages. For example, choosing adherent producer cell lines for OV production could result in difficulties when the project begins to scale, with larger requirements for floor space as compared with suspension cultures.
Finding the right support
Easing the pressures manifested by demand for speed to IND application combined with a myriad of intricate decisions that must be made during OV development and manufacturing can be achieved by seeking expert support. Finding those with extensive experience producing products in this new therapeutic area, with an understanding of the implications of each decision, can simplify an often convoluted process.
As a global contract development and manufacturing organization (CDMO) with expertise in OVs, Vibalogics can help to advance your innovation through clinical trial phases and beyond. For more information on how Vibalogics could help your OV on its journey to IND application, contact us today.
 Zhang, B., Cheng, P. Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy. Mol Cancer 19, 158 (2020).