BeiGene Moves Fast, Stays In-House To Conduct Its Cancer Clinical Trials

A conversation with Mark Lanasa, MD, Ph.D., chief medical officer, solid tumors, BeiGene

The clinical trials industry understands that it is a delicate balance of time, money, and talent (and likely a little bit of luck) that makes the pursuit of a promising new pharmaceutical drug successful, let alone possible. The industry also understands that though there are successes, they are preceded and surrounded by many failures.

That’s why BeiGene is taking a somewhat paradoxical approach to the traditional industry R&D models, essentially building a large early-stage pipeline that enables them to take “multiple shots on goal” and run dozens of clinical trials, says CMO, Solid Tumors Marka Lanasa, MD, Ph.D.

In this Q&A, discover how Lanasa and his team uphold their mission of getting innovative medicines to more patients around the world — enabled in part by an ability to realize strategic cost and time advantages of a unique (and fast) R&D approach and a decision to bring clinical operations in-house.

Clinical Leader: You’ve appeared to flip the industry model on its head. How is this “multiple shots on goal” approach efficient?

Mark Lanasa, MD, Ph.D.: Drug development is a challenging and failure-prone endeavor, and we view clinical proof of concept (PoC) as the biggest value inflection point for a molecule. Industrywide, more than two-thirds of the cost of developing a cancer drug is spent in late-stage clinical trials, and it’s our view that early clinical signals are the most informative data on which to base those investment decisions. Our discovery research team has established a “Fast to PoC” initiative to quickly explore the clinical potential of many molecules in parallel, at a low incremental expense. We believe this model will yield better quality data in shorter timelines and at lower cost, which we can translate into more affordable innovation for cancer patients globally.

Having been founded in 2010, we are still a fairly young company, but in our first 11 years, we brought three internally discovered molecules to market, including two globally approved cancer medicines, BRUKINSA and TEVIMBRA. As we’ve matured, we have built out a full range of pharmaceutical development functions that we are now in a position to leverage and realize what we sometimes call “innovation at scale” — and you can see this in the growth of our pipeline. We have advanced more than 10 new molecules into the clinic in the last year, with several more on deck to enter Phase 1 before the end of 2024.

“Proof of concept” can have various meanings across the industry. When you talk about a “Fast to PoC” strategy, what does that mean for BeiGene?

For us, Fast to PoC is a portfolio management initiative to streamline several critical steps in early drug development. The goal is to generate clinical data that inform our later-stage program investments, both in terms of go/no-go decisions as well as dosing, combination therapies, and indications. Depending on the molecule and its intended development path and indication, we establish criteria for success based on current standards of care, so that we are targeting clinically meaningful patient impact. These criteria are established prior to starting the clinical trial, and we must retain discipline and stick to these criteria to enable high-quality decisions. Generally, in addition to acceptable tolerability, we look for activity demonstrating proof of mechanism and signs of potential efficacy, which then give us further confidence in a novel molecule we are developing. 

Now that we understand the foundation for your Fast to PoC strategy, tell us more about it. What does that approach look like in action?

BeiGene’s Fast to PoC strategy is inclusive of several elements covering the progress of a program, from preclinical candidate nomination through early clinical development data readout. Our Fast to PoC initiatives incorporate program management activities, metrics, and gating criteria to support efficient decision-making.

Some of the areas of focus for Fast to PoC include:

• accelerating preclinical cycle times, which means doing as many things as we can in parallel during preclinical development of a molecule
• manufacturing of clinical material in-house, which does require a large up-front cost but has tremendous value over time in accelerating our programs
• running clinical operations in-house and using protocol automation technologies, which help streamline study initiation and execution
• reducing cycle times for dose escalation cohorts, with avid attention to sites and patient screening activities to keep the cadence going
• optimizing the dose concurrent with dose escalation, meaning that within physiologically relevant ranges, we continue to enroll at lower dose levels while also enrolling at the higher levels to gain the best understanding of exposure responses
• minimizing white space from dose escalation to dose expansion, which involves being ready with amendments as data come in to ensure we are moving seamlessly to dose expansion phases.

How is this different from the remainder of BeiGene or other pharmas’ approaches to clinical programs? 

Accomplishing Fast to PoC is an organization-wide, cross-functional effort, and our established internal capabilities to fully control and coordinate preclinical, manufacturing, regulatory, and clinical development activities are key enablers. Clinical operations in particular is an area where BeiGene has taken a different approach from many of its pharma peers. Several years ago, we set out to reduce reliance on third-party CROs by extensively building out our internal clinical operations function, and we are now executing 100% of our clinical trials in-house. This not only allows us to ensure consistency and quality but also facilitates our operational urgency as we work directly with sites and investigators in over 45 countries across our portfolio of over 100 active studies.

Part of what drives our efficiency is the early clinical development network we have established, working directly with investigators, sites, and regulators in concert. Through engaging this model in Australia and the United States especially, we have been able to scale our Phase 1 clinical development capabilities to meet the demands of our growing pipeline and achieve our aggressive goals for study start-up and enrollment times. While most of our global first-patient-dosed milestones do come from these two countries, this network model is regionally customizable. This is important for targets where the epidemiology might lead you to a particular geography. For example, we recently started the development of GPC3 x 4-1BB bispecific for an indication in hepatocellular carcinoma, so for that we are initially focusing on-sites in central Europe and east Asia. This regional customization is also important so we don’t overload the same handful of sites with 10 different molecules per year, which would be a challenge for them to deliver on.

We have made other operational innovations that contribute to our efficiency. We have integrated the global clinical supply chain team within clinical operations, building a partnership that ensures the right medicines are available to the right patients at the right times. And we also have developed purpose-built technology solutions, including various digital tools and software platforms to transform traditional clinical document generation and data collection and handling practices and facilitate the most efficient data-driven decision-making.

What are the benefits of this approach as it relates to time, money, and likelihood of success? 

Our fully internal global clinical development function improves our efficiency across development, especially in the early stages as we meet our Fast to PoC metrics. Relative to industry benchmarks (within the Clarivate 2023 CMR International Pharmaceutical Factbook), BeiGene has been achieving faster study startups and trial enrollment, particularly in first-in-human studies, lower cost per patient, and improvement in overall clinical study cost and cycle times.

We’ve also been able to drive progress in increasing diversity among our clinical trial participants through initiatives in trial design, site selection, materials generation and education, patient and community engagement, and collaboration. Together, these actions have helped to address barriers to participation and ease logistical burdens, increasing the proportion of diverse patient populations enrolling and participating in our clinical trials. The integrated clinical supply chain has netted cost savings and prevented any stockouts, and consistent decision-making and execution have strengthened inspection readiness, leading to more than 75 successful health authority inspections carried out by over a dozen inspectorates across nine countries. We’ve seen quality improvements in clinical execution as well; as we transitioned from an external to an internal model, one metric I can share with you is that the average time to detection of a protocol deviation was reduced by over 100 days.

And one of the intangible benefits of our internal development model is that our investigators like it. They appreciate working directly with us, knowing who the program lead is, knowing who the medical monitor is, and knowing they can email me if they have a substantial concern. We think this enables the types of human relationships that underpin the success not only of the investigational program at hand but also of future pipeline programs.

It's too early to lay claim to improved probabilities of success, but we are certainly optimistic that our model will enable us to invest prudently in clinically impactful investigational molecules that will become the transformative medicines of tomorrow and that the development efficiencies we realize will support our mission of increasing access to innovation for cancer patients.

About The Expert:

Mark Lanasa, MD, Ph.D., joined BeiGene in February 2022 as senior vice president, chief medical officer for solid tumors. Prior to joining BeiGene, Dr. Lanasa served as vice president and global clinical head, late development oncology at AstraZeneca from 2019 to 2022. He previously held several positions at AstraZeneca, including global clinical lead and global development lead for immuno-oncology, senior medical director in clinical development, and medical director in early clinical development. Dr. Lanasa also worked as senior director of clinical development at Immunocore, where he contributed to the late-phase development of T-cell engager Kimmtrak (tebentafusp-tebn).

Dr. Lanasa earned his B.S. in chemistry from Pennsylvania State University, and both his Ph.D. in biochemistry and molecular genetics and M.D. in the Medical Scientist Training Program at the University of Pittsburgh School of Medicine. He completed his residency and was a post-graduate fellow at the Duke University Medical Center, where he was subsequently on the faculty in hematologic malignancies.