BeOne Medicine has initiated a Phase 3 clinical trial in Korea for its next-generation targeted protein degrader (TPD), BGB-16673, targeting chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The move marks a significant advance in the increasingly competitive Bruton tyrosine kinase (에볼루션 바카라) inhibitor market.

The company received regulatory approval for two Phase 3 trial protocols on July 3 and 30. One trial targets CLL/SLL patients previously treated with both BTK and BCL2 inhibitors, comparing BGB-16673 to investigator’s choice therapies: (① duvelisib + rituximab, ② bendamustine + rituximab, or ③ venetoclax + rituximab). The second trial directly compares BGB-16673 with Eli Lilly’s Jaypirca (pirtobrutinib) in patients with relapsed or refractory disease.

Currently approved BTK inhibitors in Korea include BeOne’s Brukinsa (zanubrutinib), Janssen’s Imbruvica (ibrutinib), and Lilly’s Jaypirca. These agents target BTK, a key enzyme in B-cell survival and proliferation, by suppressing its function. However, their mechanisms differ.

Imbruvica and Brukinsa are covalent 에볼루션 바카라 inhibitors that bind irreversibly to the 에볼루션 바카라 C481 residue. While effective, they are prone to resistance due to binding site mutations and long-term use may lead to side effects such as bleeding and atrial fibrillation. Jaypirca, in contrast, is a reversible, non-covalent inhibitor that binds multiple 에볼루션 바카라 sites, potentially reducing both resistance and adverse effects.

Lilly recently reported that Jaypirca demonstrated non-inferiority to Imbruvica in overall response rate (ORR) as first-line therapy in the Phase 3 BRUIN CLL-314 study. However, Imbruvica remains the leading first-line treatment in Korea, bolstered by its reimbursement status since September 2023. According to UBIST, its outpatient prescription sales rose 32.7%, from $3.15 million in 2023 to $4.16 million in 2024. Despite Brukinsa gaining reimbursement in June 2023, its second-half outpatient sales totaled just $106,000.

Jaypirca received marketing approval in August 2023 and launched non-reimbursed sales in December. It passed the Drug Reimbursement Evaluation Committee in May with a conditional request for further data, and reimbursement discussions are ongoing.

“Jaypirca demonstrated non-inferiority to the standard of care in ORR and is the only non-covalent BTK inhibitor,” a Lilly spokesperson said. “While PFS data are still maturing, we aim to prove superiority. Jaypirca is a critical option for patients with limited treatment alternatives.”

BeOne’s BGB-16673 distinguishes itself with a novel BTK degradation mechanism. Instead of blocking BTK activity, it eliminates the protein entirely, potentially overcoming resistance from BTK mutations such as C481S, L528W, and T474I. Developed using the company’s CDAC (Chimeric Degradation Activation Compound) platform, the drug showed promising results in the global Phase 1/2 CaDAnCe-101 trial, with an ORR of 84.8% and 93.8% in the recommended dose group. The 12-month progression-free survival rate reached 77.4%.

If the ongoing Phase 3 trial against Jaypirca proves successful, BGB-16673 could not only challenge existing therapies but also serve patients resistant to current 에볼루션 바카라 inhibitors.

As the Korean CLL/SLL market evolves, competition is heating up between Janssen, Lilly, and BeOne. With 에볼루션 바카라 inhibitors firmly established, the spotlight now turns to 에볼루션 바카라 degraders like BGB-16673 and their potential to reshape the treatment paradigm.