Oral Bexarotene Gains Marketing Authorization for CTCL in Hong Kong

Oral bexarotene (Targretin) has received marketing authorization in Hong Kong for the treatment of patients with cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) who are refractory to at least 1 prior systemic therapy, according to an announcement by drug developer Main Life.¹

This decision was preceded by the agent’s approval in Macau in early 2024, which together mark the agent’s first commercial availability in China.

“The availability of [bexarotene] offers patients living with the rare disease in Hong Kong the option of a drug considered standard of care in international clinical practice,” the company stated in a news release.

Bexarotene, the active substance in this compound, is a retinoid that is thought to selectively bind to the retinoid X receptor and suppress tumor growth by inducing apoptosis and cell cycle arrest. However, the exact mechanism of action of bexarotene in the management of CTCL is unknown.²

Bexarotene capsules received FDA orphan drug designation in 1999 for the treatment of patients with pretreated CTCL in the United States (US), and as of December 2022, the therapy is available for this indication in 36 countries or regions.¹ Additionally, the National Comprehensive Cancer Network and European Organization for Research and Treatment of Cancer guidelines both recommend bexarotene as a treatment option in this setting. The recommended initial dose of bexarotene is 300 mg/m² daily with a meal. Dose adjustment to 200 mg/m² daily followed by 100 mg/m² daily is permitted.²

The efficacy and safety of bexarotene in patients with advanced and early stage CTCL has been evaluated in 2 multicenter, open-label, historically-controlled clinical trial that were conducted in the US, Canada, Europe, and Australia. The studies enrolled a combined population of 152 patients, 102 of whom had disease that was refractory to at least 1 prior systemic therapy, 90 of whom had advanced disease, and 12 of whom had early disease. Patients with advanced disease were refractory to at least 1 prior systemic therapy, had received a median of 2 (range, 1-6) prior systemic therapies and had been treated with a median of 5 (range, 1-11) prior systemic, irradiation, and/or topical therapies. Patients with early disease were intolerant to, had disease that was refractory to, or had reached a response plateau of 6 months on, 2 or more prior therapies. Overall, patients in these trials had received a median of 3.5 prior therapies (range, 2-12), including systemic, irradiation, and/or topical therapies.

Patients were initially treated with a starting dose of 650 mg/m² with a subsequent reduction to 500 mg/m² per day; however, the starting dose was further reduced to 300 mg/m² as neither of the initial starting doses was well tolerated.

At the recommended initial dose of 300 mg/m², a complete response rate of 1.6% and a partial response rate of 30% were observed among 62 evaluable patients. The rate of relapse in the 20 responders was 30% over a median duration of observation of 21 weeks, and the median duration of tumor response had not been reached. Responses were observed as early as 4 weeks.

The mean duration of treatment for the 152 patients with CTCL was 166 days. The most common treatment-related adverse effects observed in greater than 10% of patients included: hyperlipidemia, hypercholesteremia, headache, hypothyroidism, asthenia, leukopenia, rash, nausea, infection, peripheral edema, abdominal pain, and dry skin. The bexarotene capsules are contraindicated in patients with a known serious hypersensitivity to bexarotene or other components of the product.

References

1. Main Life received Targretin (bexarotene) marketing authorisation in Hong Kong for cutaneous T-cell lymphoma. Main Life Corporation Limited. July 16, 2024. Accessed July 16, 2024. https://www.globenewswire.com/news-release/2024/07/16/2913485/0/en/Main-Life-received-Targretin-Bexarotene-Marketing-Authorisation-in-Hong-Kong-for-Cutaneous-T-Cell-Lymphoma.html
2. Targretin. Prescribing information. Bausch Health. April 2020. Accessed July 16, 2024. https://pi.bauschhealth.com/globalassets/BHC/PI/TargretinCapsules-PI.pdf