Takeda's Brentuximab Vedotin Receives NMPA Approval for Two New Indications in Cutaneous T-Cell Lymphoma

On April 16, Takeda China announced that its brentuximab vedotin for injection had received formal approval from the National Medical Products Administration (NMPA) of China for the treatment of adult patients with CD30-positive primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF) who have previously received systemic therapy. This marks the approval of two new indications in China for brentuximab vedotin for injection, following its initial approval in May 2020 for the treatment of adult patients with CD30-positive relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) and relapsed or refractory classical Hodgkin lymphoma (cHL).

Primary cutaneous anaplastic large cell lymphoma and mycosis fungoides are the most common major subtypes of cutaneous T-cell lymphoma (CTCL). CTCL comprises a group of relatively rare mature T-cell lymphomas that primarily involve the skin. Most cases present as erythematous, scaly patches or thickened plaques, causing extensive skin damage. The disease is debilitating and disfiguring, severely impairing skin aesthetics and function, imposing a substantial physical and psychological burden on patients; if complicated by severe infection, it can even be life-threatening. Among these, mycosis fungoides is the most prevalent, accounting for approximately 60% of cases.

As a cutaneous hematologic malignancy that is difficult to cure, cutaneous T-cell lymphoma (CTCL) generally progresses slowly. However, due to the rarity of the disease, long-term standardized diagnosis and treatment are currently insufficient, leading to challenges such as low diagnostic rates and frequent medical visits for patients. Meanwhile, as the disease duration prolongs, patients often face recurrence, making treatment more challenging. Currently, therapeutic options for primary cutaneous anaplastic large cell lymphoma (pcALCL) and mycosis fungoides (MF) are limited. Conventional treatments, including topical medications and phototherapy, have limited efficacy, resulting in patients’ inability to participate normally in social activities or even perform self-care, which severely impacts their quality of life. There is an urgent need for higher-quality innovative therapies to alleviate these treatment challenges, improve complete response rates, and enhance patients’ quality of life.

The formal approval of the new indication for brentuximab vedotin for injection is expected to address the urgent, unmet treatment needs of patients in China with primary cutaneous anaplastic large cell lymphoma and mycosis fungoides. This approval was primarily based on a Phase III, randomized, open-label, multicenter clinical study. According to data assessed by an independent review committee, both the primary and secondary endpoints demonstrated superior efficacy of brentuximab vedotin compared to the control group: the objective response rate at 4 months (ORR4) was significantly improved in the brentuximab vedotin group versus the control group (56.3% vs. 12.5%). Regarding key secondary endpoints, brentuximab vedotin showed a statistically significant advantage, with a higher complete response rate (CR) (15.6% vs. 1.6%) and significantly improved progression-free survival (PFS), yielding a median PFS of 16.7 months (vs. 3.5 months). In terms of safety profile, monotherapy with brentuximab vedotin was consistent with the previously established safety profile of brentuximab vedotin monotherapy. Based on these study data, brentuximab vedotin was granted a waiver for registrational clinical trials in China, substantially shortening the time to market for the new indication and enabling faster access for Chinese patients.

Brentuximab vedotin for injection is the world’s first antibody-drug conjugate (ADC) targeting CD30. It comprises a monoclonal antibody targeting the CD30 protein conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-sensitive linker. Upon internalization by CD30-positive tumor cells, brentuximab vedotin releases MMAE, thereby specifically inhibiting tumor cells expressing CD30. Studies have shown that CD30 protein is expressed in approximately 50% of lesions in patients with cutaneous T-cell lymphoma. Currently, brentuximab vedotin has been approved for the treatment of lymphoma in more than 70 countries and regions worldwide. It has been granted orphan drug status for the treatment of mycosis fungoides and cutaneous T-cell lymphoma (including primary cutaneous anaplastic large cell lymphoma [pcALCL] and mycosis fungoides [MF]) in the United States and Europe, respectively.

Note:

1. Willemze R, et al. Blood. 2019;133(16):1703-1714.

2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines).

3. Lancet. 2017 Aug 5;390(10094):555-566.

4. ADCETRIS  HIGHLIGHTS OF PRESCRIBING INFORMATION

5. Senter PD, Sievers EL. Nat Biotechnol. 2012;30(7):631-7.

6. Mulvey E, Ruan J. J Hematol Oncol. 2020;13(1):59.

Responsible Editor: Liuli

Disclaimer: This article is reposted from Yaozhi.com. The copyright belongs to the original author. The purpose of reposting is to convey more information, which does not represent the views of this platform. If there are any issues related to the content, copyright, or other matters, please leave a message on our website, and we will remove the content promptly!