The Oncology Drug Race Has Reached a New Height

How to become the leader in the field of oncology? In the past few years, Johnson & Johnson has taught the market a lesson in the field of multiple myeloma.

From monoclonal antibodies to CAR-T and then to bispecific antibodies, the treatment lines have been extended from first-line to last-line: Through a progressive, broad yet precise layout, Johnson & Johnson has built a higher moat for itself while leaving less room for newcomers to break through.

The Growth of Multiple Myeloma Leadership in Progress. Currently, Johnson & Johnson's well-structured transition is taking shape, with related product revenue breaking through the 10 billion USD mark in 2023.

But such a story is destined not to belong only to Johnson & Johnson.Any powerful pharmaceutical company has its own unique core capabilities, corresponding to a smooth product portfolio梯队 management system and "approach."

It can be seen that many capable pharmaceutical companies are also telling such stories, such as the well-known BeOne Medicines in the market.

In the field of hematological tumors, with the BTK inhibitor zanubrutinib as the foundation, BeOne Medicines' BCL2 inhibitor, BTK CDAC, and other pipelines are advancing rapidly, revealing a broader landscape.

This perhaps also suggests that the competition in cancer drugs has unconsciously reached a new level.

/ 01 / Promote Significant Uptrend

In the era of great technological exploration, new drug combinations are emerging endlessly, posing higher demands on the incumbents; naturally, the "incumbents" will not sit idly by but will prepare in advance and proactively adapt to changing demands.

Under this logic, the competition in tumor drugs continues to intensify. BeOne Medicines' layout in hematological tumors also offers a clearer view of this trend.

Especially in the field of CLL, as the largest indication for BTK inhibitors, competition is fierce. At this year's ASH Annual Meeting,AMPLIFY Phase 3 Study Evaluates "Acalabrutinib (Akecitinib) + Venetoclax" Combination as Fixed-Duration Therapy for Previously Untreated CLL, Drawing Significant Attention.

Although the "A+V" combination logic remains to be validated, in the meantime, BeOne Medicines is signaling to the market that a new variable has emerged.

At the ASH Annual Meeting, the Phase 1/1b study data published by BeOne Medicines showed,The "BCL-2 inhibitor sonrotoclax + zanubrutinib" (hereinafter referred to as ZS) combination has the characteristics of "rapid onset" and "deep and durable relief."

Specifically:

Combined regimen undetectable minimal residual disease (uMRD)High incidence and early onset, the uMRD4 rate at 24 weeks of treatment had already reached 78%, with the depth of response continuing to improve over time until 48 weeks (91%). AndAs of the data cutoff date (median follow-up time was 19.4 months), no patients converted from MRD4-negative to MRD4-positive.

Since the uMRD4 rate is closely related to patients' progression-free survival (PFS) and overall survival (OS), serving as a crucial parameter for evaluating treatment efficacy and prognosis, the aforementioned data reflects the "ZS" combination's effectiveness and also suggests potentially higher dominance in the future.

In contrast,At similar time points, patients receiving ZS treatment achieved more favorable uMRD4 compared to those receiving AV/AVO/chemotherapy.Although not head-to-head data, considering that the Phase 1/1b study is one of the clinical trials with the highest inclusion of high-risk characteristic groups globally, it has relatively strong persuasiveness.

The prominent safety data further guarantees this point. In the Phase 1/1b study,Most TEAEs in the ZS combination were low-grade, and the most common ≥3 grade TEAEs were mostly transient.

Adding the ZS combination for the TN CLL registration clinical trial, isThe only global Phase 3 trial aimed at demonstrating superior PFS compared to the standard treatment of venetoclax + obinutuzumab, which is expected to further solidify BeOne Medicines' position in the TN CLL market.

The logic driving the heightened industry competition is also reflected in BeOne Medicines' BTK CDAC BGB-16673.

In the past few years, the biggest disruptor in the BTKi market has undoubtedly been the emergence of the non-covalent BTK inhibitor pirtobrutinib, which not only addresses the needs of patients with drug resistance, achieving a differentiated competitive edge, but also has the potential to overturn the landscape of covalent inhibitors.

Based on this, BeOne Medicines has strategically played the BGB-16673 card. At this year's ASH Annual Meeting, BGB-16673 also showed its prowess.

Specifically, BGB-16673 still demonstrated promising results in the population of R/R CLL/SLL patients who had received multiple prior lines of therapy.Excellent safety and tolerability, with no cardiac toxic side effects typically associated with traditional BTK inhibitors observed so far, and a relatively low incidence of bleeding.

Meanwhile, BGB-16673 demonstrated significant anti-tumor activity. In the cohort of CLL/SLL patients (median number of prior treatment lines: 4),BGB-16673 Achieves an ORR of 94% at a 200mg Dose, with a More Favorable Predicted PFS Compared to Pirtobrutinib.

In patients with more difficult-to-treat Richter’s transformation, it also demonstrated good activity, with an ORR rate of 58.3%, potentially superior to pirtobrutinib.Also at this year's ASH annual meeting, the ORR for pirtobrutinib in this patient population was announced to be around 50%. Based on the data from relevant studies, BeOne Medicines plans to initiate a head-to-head study of BGB-16673 versus pirtobrutinib in 2025.

Obviously, the emergence of BGB-16673 has provided more answers regarding the direction of the BTKi dynasty's transition. As for BeOne Medicines itself,Through the layout of three core products, it has covered the entire treatment process for CLL patients.

In the competition within the BTKi market, as the subtle shift between "offensive" and "defensive" strategies occurs, the complexity and difficulty of the competition have significantly increased.

/ 02 / A Grand Narrative

In fact, for leading oncology pharmaceutical companies, the focus is not just on a single pipeline but on their ability to work collaboratively. These companies often maximize the potential of each pipeline through powerful combinations. This is the core reason why top oncology pharmaceutical companies carry out extensive and precise strategic layouts.

BeOne Medicines is no exception. It can be seen that the three key products launched by the company — zanubrutinib, sonrotoclax, and BGB-16673 — are not just for defense but also for "offense," aiming to achieve more "market capture" plans in the field of hematological tumors.

The core idea is to achieve different combinations through these three differentiated molecules.On the one hand, it meets the treatment needs of various lines, and on the other hand, it expands to areas with significant unmet needs.HealthcareNew indications for demand.

For example, in BeOne Medicines' vision, the goal of sonrotoclax is to become the BCL-2 inhibitor with the broadest range of indications:

In addition to maintaining and enhancing its leadership position in CLL and other B-cell malignancies, it will also expand into AML and is expected to be the first approved BCL-2 inhibitor for MM with t(11,14).

As shown in the figure below, the phase 3 clinical trials of sonrotoclax for untreated CLL/SLL (TN CLL/SLL) and relapsed or refractory MCL (R/R MCL) are both accelerating. These studies are all conducted in combination with zanubrutinib.

In addition, sonrotoclax has also been put on the agenda for Phase 3 clinical trials targeting indications such as TN WM and 1L AML through different combinations.

In the CaDAnCe-101 clinical trial, we can also see BeOne Medicines' high expectations for BGB-16673.

First,"It's about 'moving forward' to address resistance issues across multiple indications."In its CaDAnCe-101 clinical trial, a total of 7 cohorts were set up, comprehensively covering different types of B-cell hematologic malignancies.

Secondly, it is "moving forward." The 1C cohort in the CaDAnCe-101 clinical trial is already exploring the earlier-line treatment of BGB-16673 as a monotherapy in the BTK-naïve cohort. Furthermore, in the future, it may advance further by combining with agents including sonrotoclax, zanubrutinib, and CD20xCD3 bispecific antibodies.Promote the "chemotherapy-free" approach in B-cell tumors.

In other words, BeOne Medicines aims to elevate the overall competition in the field of hematological tumors to a new strategic level through a carefully planned pipeline combination strategy.

Although it remains to be seen whether BeOne Medicines' ambitions can be realized, one thing is certain: they have provided us with another dimension to understand the competition in hematological tumors—ecosystem-based strategies lead to a higher ceiling.

/ 03 / A Trend of the Times

The emergence of BeOne Medicines' sonrotoclax, BTK CDAC, and other pipelines is not accidental. In previous plans, the company had already clearly mentioned that the future growth of hematological tumors would follow a "multi-step strategy."

The first step is to consolidate the leadership position through zanubrutinib.

The second step is to expand the leadership position through sonrotoclax and BTK CDAC.

The third step is to expand the portfolio through different combinations of three differentiated molecules.

Step Four: Maximize Its Influence in the Field of Hematological Tumors.

And nowAs BeOne Medicines continues its rapid rise, it has reached a stage of accelerating strategic advancement and embracing the next wave of products.

On the one hand, zanubrutinib has shown strong performance as the next-generation BTK inhibitor with the broadest globally approved indications and a leading position in the newly diagnosed CLL market, supporting BeOne Medicines' expansion logic.

On the other hand, its globally unique clinical quality and efficiency ensure that while it expands its reach, it can also widen the gap with competitors.

A typical example is,The number of patients enrolled in the key clinical trials of sonrotoclax has expanded from 800 at the end of the first quarter to over 1,600 currently.In other words, BeOne Medicines ensuredApproximately 100 people per monthThe enrollment efficiency.

This is an astonishing speed. According to the McKinsey report, even for large varieties like PD-1 globally,The average number of patients enrolled per month is around 0.3 to 0.5, while for patients like those with GLP-1, the average is about 2 per month.And for sonrotoclax, which targets hematological tumors, the patient population is relatively smaller, and the difficulty of enrollment will also be greater.

Because of this, the pipelines laid out by BeOne Medicines, such as sonrotoclax and BTK CDAC, will accelerate their appearance in the public eye. Moreover, it is not only in the field of hematological tumors but also includes more pipelines in the field of solid tumors.

At the recent San Antonio Breast Cancer Symposium, the leading lineup featuring the CDK4 inhibitor BGB-43395 showcased the comprehensiveness and rapid progress of BeOne Medicines in the breast cancer field. To date,More than 120 patients have been enrolled in the BGB-43395 clinical trial within one year of its initiation.，enough to keep pace with competitors.

This also means that the story of increasingly fierce competition is not only unfolding in the field of hematological tumors but also in solid tumors.

This also reflects a trend of the times:

In the era of great technological exploration in the biopharmaceutical industry, the iteration of technology is extremely rapid, and the mindset and level of competition are constantly evolving. With the emergence and maturation of more ambitious pharmaceutical companies like BeOne Medicines, this process has been further accelerated.

How pharmaceutical companies can do more is driven by "certainty," a natural outcome of the accumulated advantages from years of efforts by the company and its team. This requires more pharmaceutical companies to comprehensively enhance themselves. Only by building more core competencies can they create more possibilities for the future.

       Title: Oncology Drug Competition Reaches New Heights