Putting Patients First: The Quest to Make Anticancer Cell Therapy Accessible to All

As cell therapies continue to rank among the most expensive of cancer treatments, BeiGene is quietly charting a different path that would enable more equitable access for all.

With the inauguration of a new state-of-the-art cell therapy lab in early 2022, BeiGene is looking to broaden collaboration and expand capability in the field of anticancer cell therapy. Founded in 2010, BeiGene, a commercial stage global biotech company focused on the development of cancer treatments, already has three new molecular entities approved in several countries/markets around the world, and possesses a diverse pipeline of novel oral small molecules and monoclonal antibodies in varying stages of development. BeiGene only made its first foray into anticancer cell therapy in June 2021, via a collaboration agreement signed with Shoreline Biosciences, a California-based biotech company specializing in natural killer cell therapies.

The cell therapy unit at BeiGene is currently headed by Dr. Alex Huang, Vice President and Head of Cell Therapy, a 20-year industry veteran whose career spans some of the biggest names in biotech and pharma, including Novartis, Sanofi, Genentech, Bristol-Myers Squibb, and AbbVie, during which he participated in or oversaw the development of several new anticancer drugs and biomarker-based diagnostics. Dr. Huang strongly believes that cell therapy could be the spearhead to a transforming breakthrough in cancer treatment, not just in hematological oncology, for which the vast majority of cell therapies are currently approved, but also against solid tumors.

Related article: Cell Therapy as a Pillar of Future Therapeutics, an Interview with Alex Huang, Vice President and Head of Cell Therapy at BeiGene

Charting a New Path in Cell Therapy Development

“At BeiGene, it’s all about putting patients first,” stated Dr. Huang, and this philosophy is deeply integrated across the entire R&D process, from enhancing the efficiency of research and development to reduce the cost of treatment, to designing truly global trials that include developing countries in addition to developed countries, and to displaying a respectful willingness to listen and respond to feedback and suggestions from collaborating clinicians. Dr. Huang emphasized that BeiGene not only sought to develop effective anticancer cell therapies, but was also committed to making such treatments affordable and accessible to all patients in need.

Cell therapies can be broadly classified into two types: “autologous,” meaning therapies developed with the patient’s own cells, and “allogeneic,” therapies developed with cells derived from individuals other than the patient. Among the 23 cell therapies approved by the US FDA at the time of this writing, 15 are indicated for use in hematological oncology. Of these, only 6 approved therapies can actually target and clear cancer cells to effect a cure, all of which are autologous chimeric antigen receptor T-cell (CAR-T) therapies. In CAR-T therapy, T cells are extracted from the patient, genetically edited in the lab to recognize markers or receptors specific to cancer cells, then expanded to increase cell numbers, and finally infused back into the patient to hunt down and eliminate the targeted cancer cells. Following CAR-T therapy, complete response, defined by the absence of all signs of cancer, has been reported in 40-98% of patients, depending on the type of cancer and CAR-T treatment. However, this comes with a hefty price tag, with the average cost of care reported to be over US$ 600,000, a figure out of reach for all but the wealthiest of patients.

In light of the varying response levels and high costs of current anticancer cell therapy, Dr. Huang noted that BeiGene was not limiting research to natural killer cells or any specific platform, as there was no single best approach, and different platforms all had their own respective strengths and weaknesses. However, to make cell therapies widely affordable, allogeneic cell therapy based on induced pluripotent stem cells (iPSC) was likely to be an important focus of research going forward.

Pivoting Longstanding Collaborations to Address New Challenges

The concept of allogeneic CAR-T or other anticancer cell therapy is not new, and a handful of products have advanced to early clinical trials, but challenges such as maintaining the integrity of allogeneic cell cultures, ensuring patient compatibility, and preventing allorejection continue to hold the field back. In spite of these challenges, Dr. Huang believes that allogeneic cell therapies developed from iPSC may be able to avoid the problems of patient compatibility and allorejection, while also enabling culture, manufacturing, quality control, and clinical application to become standardized, and even automated to some extent. To this end, BeiGene has been reaching out to longstanding collaborators to explore possibilities and develop R&D strategies going forward.

Recently, Dr. Huang invited Professor Constantine S. Tam, Professor of Hematology at Monash University and Head of the Lymphoma Service at Alfred Hospital Health in Melbourne, Australia, to visit the new BeiGene cell therapy lab and engage in a high-level dialogue on the future development of cell therapy. Professor Tam is a renowned clinical hematologist who has served as principal investigator for several important clinical trials of new therapies in Australia, including the BeiGene-developed Brukinsa (zanubrutinib) and Tislelizumab. Importantly, Professor Tam noted that, “no single approach can achieve complete eradication of cancer,” and future treatment strategies could likely involve combinations of cell therapy and various targeted therapies to attack cancers from different pathways simultaneously, thereby increasing the chance of breaking through cancer cell defenses while also reducing the likelihood of resistance.

Can Cell Therapies become Widely Accessible?

Although Dr. Huang and Professor Tam hail from very different backgrounds, their respective decades of expertise had brought them together to BeiGene’s newest R&D facility for cell therapy research. Professor Tam was impressed that the science is already moving quite quickly even though it had been in operation for just a short while. Here, the industry-renowned “BeiGene Speed” of bringing medicines as quickly as possible to patients was apparent. About 10 years ago, Professor Tam began collaborating with BeiGene on conducting clinical trials for the novel BTK inhibitor Brukinsa, which has since been approved in over 65 countries and regions worldwide as of today, benefiting tens of thousands of patients. Now, 10 years later, it is exciting to see if the previous success can be replicated to develop effective and affordable cell therapies that are widely accessible.

Professor Tam was confident that allogeneic cell therapies represented the future. “Currently, there is too much variability in autologous cell therapy,” stated Professor Tam. “From the start, the number and quality of cells obtained during the extraction process varies between patients. This can affect subsequent processing and expansion, and eventually, the number of genetically modified cells that each patient receives is different as well. Since each treatment has to be tailored to the condition of each individual patient, the entire process is inefficient, costly, and not really standardized.” Dr. Huang concurred, noting that “allogeneic cell therapies would allow us to standardize and streamline the production process, thereby lowering costs and enabling us to develop treatments that are readily accessible and easily affordable for patients.” Dr. Huang also noted that this had the potential to make cell therapy an attractive and worthwhile reimbursement option for both public and private insurance, further reducing expenses for patients.

As for the potential regulatory hurdles to gaining approval for allogeneic anticancer cell therapies, Professor Tam responded, “If regulatory agencies can accept the level of variability associated with autologous CAR-T, then there is no reason why they would not approve an allogeneic therapy that has standardized production and quality control parameters, standardized dosing, and strong clinical evidence to guide its effective and safe use.” He also drew on his extensive experience of conducting clinical trials in the Melbourne public hospital system, where he has spent almost his entire medical career, noting that the relative openness of the Australian regulatory authorities to clinical trials of new medicines, together with the strong network of the Melbourne public hospital system, where patients that are eligible for specific clinical trials can be readily referred between different hospitals, as contributing to a conducive environment to validating new therapies and approaches.

A Patient-Centered Approach to Ensuring Equitable Treatment Access

At a time when excessive drug pricing and the high cost of novel cell and gene therapies dominate the headlines, the patient-first approach of BeiGene is refreshing, and the successful collaboration between Dr. Huang and expert clinicians such as Professor Tam could spark a revolution in healthcare, to enable equitable access to cutting-edge therapies for all those in need.

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