Pharma News Update - Bruton Tyrosine Kinase Inhibitors

April 6, 2023: Update on IMBRUVICA® (ibrutinib) U.S. Accelerated Approvals for Mantle Cell Lymphoma and Marginal Zone Lymphoma Indications

Summary: AbbVie announced the intent to voluntarily withdraw, in the U.S., accelerated IMBRUVICA® (ibrutinib) approvals for patients with the blood cancers mantle cell lymphoma (MCL) who have received at least one prior therapy and with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.

Key Takeaways:

  • Imbruvica is withdrawn from the US market for patients with MCL and MZL based on the negative results in the outcome of the confirmatory trials for the MCL and MZL indications.
  • Other approved indications for IMBRUVICA in the U.S. are not affected. This voluntary action is due to requirements related to the accelerated approval status granted by the U.S. FDA for MCL and MZL. These indications were approved via this pathway based on overall response rates in Phase 2 clinical studies. To confirm clinical benefits following accelerated approvals, additional studies are required by the FDA.
  • In the United States, Healthcare professionals should consider the withdrawal of these indications in their treatment plans for patients with MCL and MZL currently taking IMBRUVICA.
  • Price of the Imbruvica has been increasing continuously despite the withdrawal of the drug in various indications coupled with the increasing competition among the BTK inhibitors market.

KOL Opinion:

“We pursued accelerated approvals for MCL and MZL indications for IMBRUVICA in the U.S. to offer treatment to patients who at the time had limited therapeutic options. While we are disappointed in the outcome of the confirmatory trials for these indications, we remain confident in the benefit/risk profile of IMBRUVICA for patients living with multiple forms of blood cancer around the world,” - Roopal Thakkar, senior vice president, chief medical officer, AbbVie.


  • The Phase 3 SHINE (NCT01776840) study in previously untreated MCL and the Phase 3 SELENE study (NCT01974440) in relapsed or refractory MZL served as confirmatory studies. The SHINE study met its primary endpoint of progression-free survival. The addition of IMBRUVICA to chemoimmunotherapy was associated with increased adverse reactions compared to the placebo-controlled arm. The SHINE study results were presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and were published in The New England Journal of Medicine.  The SELENE study did not meet its primary endpoint of progression-free survival. The SELENE study results will be presented at a future scientific forum.
  • IMBRUVICA's established clinical profile in other approved indications is unchanged and the medication remains the most comprehensively studied and prescribed cancer treatment in its class. IMBRUVICA remains an important therapy for patients and healthcare professionals around the world.


  • Acalabrutinib is expected to grab most of the share of MCL patients treated with BTK inhibitors owing to the accelerated approval (Aug 2022) of acalabrutinib in the United States for refractory MCL patients where it is the only drug in the US market dealing with MCL patients whosever is in need of BTK inhibitors.
  • Pirtobrutinib recently received accelerated approval (Jan 2023) for relapsed or refractory MCL patients after at least two lines of systemic therapy, including a BTK inhibitor would become the strong competitor for acalabrutinib in the present United States BTK inhibitors market for MCL patients.
  • Recent FDA approval of zanubrutinib on 19th Jan 2023 in the United States for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) is anticipated to create a significant market share in the BTK inhibitors market. However, a focus on accelerated approval of zanubrutinib in MCL and MZL patients in the US would offer significant market share owing to the impact of the intent to withdraw in the US for MCL and MZL patients.
  • The continuous increase in the price of ibrutinib despite the launch of competitors molecules such as zanubrutinib, acalabrutinib, and pirtobrutinib in the United States would highly impact the sales of the ibrutinib.