Advancing clinical development in haematology oncology

In the past couple of months, BeiGene has experienced regulatory progress for two of its oncology assets in clinical development. The BTK inhibitor BRUKINSA^® (zanubrutinib) was recommended by the EMA’s human medicines committee last month. Additionally, the company’s anti-PD-1 antibody achieved EU approval for oesophageal cancer in September 2023.

According to Data Bridge Market Research, the haematology/oncology market will value $14.83 billion by 2029.¹

In this Q&A, Vice President of Medical Affairs, Europe at BeiGene, Dr Jan-Henrik Terwey, covers the upcoming data presentation for the company’s BCL-2 inhibitor sonrotoclax at the upcoming 2023 American Society of Hematology (ASH) meeting, the impact drug shortages are having on clinical trials for haematology/oncology, as well as the major changes he anticipates will impact Europe clinical development within the next five years.

What is the main challenge in advancing a drug through the clinical development process? How can this be overcome?

Developing a new medicine is one of the most R&D-intensive and complex processes across all industries, requiring heavy investment. Clinical trials account for over 90 percent of the cost and time of developing a new medicine.²

One of the challenges that we have in treating cancer is that the human immune system is highly complex. This requires modulating different components of the human immune system in a way that can address different patient segments, as the immune system is dysregulated in different ways across different tumour types.

However, advancements in genomics and molecular profiling allowed for more precise and personalised treatment strategies treating sub-populations of patients with the aim to deliver the right drug to the right patient. While this is great progress, it is also associated with higher complexity regarding clinical trial design and potential regulatory challenges.

Can you share an exciting development of a recent/ongoing BeiGene clinical trial?

Freshly arrived at BeiGene, I am truly excited by our robust and diverse pipeline. From 2024, we anticipate bringing ten new candidates into clinical trials per year, spanning many mechanisms, modalities, and targets, and addressing solid tumour and haematological malignancies.

We have already established a strong foundation in the haematology space with zanubrutinib. BeiGene will be sharing exciting data for two further assets at the upcoming ASH meeting in December 2023: sonrotoclax, our BCL-2 inhibitor, and our BTK-targeted protein degrader, BGB-16673.

One recent highlight for the sonrotoclax development programme includes an encouraging 100 percent overall response rate in 56 assessed patients, with no progression reported, in our ongoing Phase I/II trial of sonrotocax in combination with zanubrutinib in patients with treatment naïve chronic lymphocytic leukaemia /small lymphocytic lymphoma. Based on these data, BeiGene is planning to initiate a pivotal Phase III in this setting.

What is the top consideration for generating valuable evidence in clinical trials?

One key objective in late-stage clinical development is to generate clinical data that supports the assessment of the benefits and risks of a medicine in the population who will ultimately receive the treatment. It is crucial that the subjects studied in clinical trials are sufficiently diverse and representative to inform decision-makers globally and support the clinical case for our treatments in different patient subgroups and well as in diverse health care systems. We are addressing this at BeiGene by delivering a clinical trial footprint that is truly global; our trials run in over 45 countries thereby aiming at supporting more equitable access to healthcare.

What is the primary step the industry can take to mitigate the impact of drug shortages on clinical trials in Europe?

Drug shortages and supply chain issues are a major challenge in the haematology/oncology space for multiple reasons; this is also reflected in clinical trials. We seek to address this by operating our own manufacturing facilities for both small molecule medicines and large molecule biologics to support ongoing clinical research and global commercialisation of our internally developed medicines. It is an area BeiGene is continuing to invest in. We are currently building a flagship US biologics manufacturing and R&D facility in Hopewell, New Jersey to complement BeiGene’s existing capabilities and offer state-of-the art, clinical- and commercial-stage biologics manufacturing.

What are the three main changes you foresee impacting clinical development in Europe in the next three to five years?

Firstly, I believe that clinical trial designs will become more complex, generating even greater data volume and diversity. We will be tapping into a wider range of rare diseases and demographics.

Secondly, I believe that the evolving regulatory landscape will impact clinical development. Regulatory bodies continuously update their guidelines and processes. The introduction of the new Clinical Trials Regulation (CTR) in the European Union, announced in March 2023, is expected to streamline and harmonise clinical trial processes across Member States.

Thirdly, I think we will be seeing more aspects of digital and technological capabilities entering clinical trial design – the likes of wearable devices and remote monitoring could make clinical trials more patient focused.

References

1. Hematology Oncology Market. [Internet] Data Bridge Market Research. Year. [cited 2023Nov]. Available from: https://www.databridgemarketresearch.com/reports/global-hematology-oncology-market.
2. Martin L, Hutchens M, Hawkins C. et al. How much do clinical trials cost? Nat Rev Drug Discov. 2017; 16, 381–382