Oncolytic viruses: Overcoming hurdles in scaling and commercialisation

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All too frequently, early-stage companies are failing to get the drug they've developed to market. Scaling up and commercialising new products comes with many challenges including: meeting commercial requirements; regulatory compliance; and securing funds for development and manufacturing. Kai Lipinski, PhD, chief scientific officer of Vibalogics, a Recipharm company, focuses on oncolytic viruses (OVs) to explain the considerations early-stage drug developers should make to help overcome these challenges and deliver their products to market successfully. 

Key insights:

  • Oncolytic viruses could be ideal for use in combination with other traditional treatments, as they have the ability to specifically target, infect, and lyse cancer cells, as well as trigger an immune response to these cells.
  • Oncolytic virus developers must make informed decisions at every step of production based on the needs of the project, from choosing between suspensions and adherent cell cultures to selecting the method of virus recovery.
  • Developers of oncolytic viruses must take time to ensure that there is a balance between quality and speed by incorporating Quality by Design (QbD) into processes as early as possible. 
  • Estimations and considerations into the volumetric production that will be needed at the final clinical or commercial scale should be made early, to prevent unexpected changes and setbacks in the more costly later stages.

Unique challenges with new oncolytic virus therapies

Advances in molecular engineering and innovative new technologies in the past 10 years have drastically broadened the drug product landscape, offering a diverse array of new or alternative therapeutics.

As we saw following the onset of the Covid-19 pandemic, novel drug modalities like mRNA vaccines can quickly and fundamentally change the way we approach challenging diseases. Similarly, new oncology therapies such as oncolytic viruses have the potential to transform the prognosis of those with cancer. Having the ability to specifically target, infect, and lyse cancer cells, as well as trigger an immune response to these cells, oncolytic viruses could be ideal for use in combination with other traditional treatments.

With an estimated 10 million deaths globally attributed to cancer in 2020 alone, the availability of new OV oncolytic virus therapies could not come soon enough. However, bringing these potentially revolutionary new therapeutics to market is not a simple task. There is always a learning curve when working with new technologies and the introduction of OVs has brought new challenges. Oncolytic virus developers have had to quickly familiarise themselves with intricate production systems and make informed decisions at every step of production based on the needs of the project. These decisions range from choosing between suspensions and adherent cell cultures to selecting the method of virus recovery and suitable analytical methods.

Considering these difficulties in mind, it is not surprising that, despite over 100 oncolytic viruses in the development pipeline, only one is currently approved for use by the FDA for metastatic melanoma (T-VEC; Imlygic).

Commercialising new oncolytic virus therapies under pressure

On the journey to market, scaling up and commercialising new OV products can raise further challenges. These difficulties can be hard to predict, particularly for those taking this path for the first time.

Critically, the product must hit critical milestones, such as a successful IND application to progress to first-in-human clinical trials. Pressure to hit these goals at an accelerated speed not only stems from the need for vital drugs to reach patients faster but from investors that wish to see a return as quickly as possible. Often, securing further funding from these groups will come with the stipulation that the project has progressed to a certain point within a set period.

As a result, there has been a growing tendency amongst developers and manufacturers of emerging technologies to take calculated risks to increase speed. Consequently, in 2020, the FDA raised several publicly acknowledged issues concerning problems relating to CMC vulnerabilities leading to serious delays.

Developers of oncolytic viruses must learn from these lessons, taking time to ensure that there is a balance between quality and speed by incorporating Quality by Design (QbD) into processes as early as possible. 

Preparing for commercial scales

Taking a proactive approach will also stand oncolytic virus developers in good stead when faced with the challenges of scaling from pre-clinical up to commercial levels. Estimations and considerations into the volumetric production that will be needed at the final clinical or commercial scale should be made early, as well as determining cell-substrate and production systems that support this scale. This will prevent unexpected changes from causing setbacks in these more costly later stages.

The production system scale and the final yield of the drug product should also be modeled to align with the intended clinical needs for patient treatments and clinical study variations. If partnering with an expert contract development and manufacturing organisation (CDMO) to support production, evaluations of scale and compatibility should also be considered early due to limitations on capacity or volumetric capability.

Looking ahead

Considering the many challenges faced by new therapeutic developers when bringing their product to market, it is no surprise that so few oncolytic viruses are currently approved for use by the FDA. Those taking on the challenges must be proactive, considering scaling early and ensuring that speed is balanced with quality. With so many factors to take into account, finding support in the form of an experienced CDMO partner could help to navigate the hurdles ahead.