FDA Grants Tentative Approval for Generic Ibrutinib

Zydus Lifesciences Limited has received tentative approval from the FDA for its generic versions of ibrutinib (Imbruvica) tablets in 140 mg, 280 mg, and 420 mg strengths.¹

This development is significant for the oncology landscape, particularly for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p deletion and Waldenström macroglobulinemia (WM), where ibrutinib plays a pivotal role. The generic availability is expected to increase access to this Bruton tyrosine kinase (BTK) inhibitor, a targeted therapy that has demonstrably improved outcomes in these B-cell malignancies.

The tentative approval is a notification to drugs that “otherwise meet the statutory and regulatory requirements for approval but cannot be approved for marketing in the United States because of patents or exclusivities related to the reference listed drug…upon which they rely,” according to the FDA.²

Ibrutinib is a small molecule inhibitor that irreversibly binds to BTK, a key enzyme in the B-cell receptor signaling pathway. This inhibition disrupts the survival and proliferation of malignant B cells, making it an effective therapeutic agent for various hematologic cancers. Its approval marked a paradigm shift in the treatment of CLL/SLL, especially for patients with the high-risk 17p deletion who historically had poor prognoses with conventional chemoimmunotherapy.

Clinical trials have established the efficacy of ibrutinib across its approved indications. For patients with relapsed/refractory CLL/SLL with 17p deletion, an integrated analysis of 3 ibrutinib studies (NCT01105424, NCT01109069, NCT01722487) involving 230 patients demonstrated an overall response rate of 85%, with estimated 30-month progression-free survival (PFS) and overall survival (OS) rates of 57% and 69%, respectively. These outcomes significantly surpassed those of other available therapies for this challenging patient population.³ Furthermore, real-world data analyses have supported ibrutinib's effectiveness as a first-line treatment for CLL/SLL, regardless of cytogenetic risk factors.⁴ While some real-world studies suggest that patients with 17p deletion may still experience inferior survival and higher rates of discontinuation due to disease progression compared to those without the deletion, ibrutinib remains a cornerstone of therapy.

In Waldenström macroglobulinemia, ibrutinib has also shown robust activity. In a phase 2 study of 63 patients with previously treated WM receiving single-agent ibrutinib, an overall response rate of 91% was observed, with a major response rate of 73%. The estimated 2-year PFS and OS were 69% and 95%, respectively.⁵ Ibrutinib can be used as monotherapy or in combination with rituximab for WM patients. A clinical trial involving 150 patients with WM (NCT02077977) demonstrated that the combination of ibrutinib and rituximab significantly reduced the risk of disease worsening or death by 75% compared with rituximab alone.⁶

REFERENCES:

1. Zydus receives tentative approval from USFDA for Ibrutinib tablets 140 mg, 280 mg, and 420 mg. News release. Zydus Lifesciences Limited. July 24, 2025. Accessed July 24, 2025. https://tinyurl.com/4fhpxrbu

2. Information for industry on FDA’s tentative approval process under the PEPFAR program. US FDA. Accessed July 24, 2025. https://www.fda.gov/media/183851/download

3. Jones J, Mato A, Coutre S, et al. Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials. Br J Haematol. 2018 Aug;182(4):504-512. doi: 10.1111/bjh.15421. Epub 2018 Jun 5.

4. Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022 Nov 1;107(11):2630-2640. doi: 10.3324/haematol.2021.280376.

5. Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med. 2015 Apr 9;372(15):1430-40. doi: 10.1056/NEJMoa1501548.

6. Dimopoulous MA, Tedeschi A, Trotman J, et al. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia. N Engl J Med. 2018 Jun 21;378(25):2399-2410. doi: 10.1056/NEJMoa1802917. Epub 2018 Jun 1.