Beleodaq (belinostat, formerly PXD-101) is a drug to treat peripheral T-cell lymphoma (PTCL) that has relapsed or failed to respond to standard treatment. It is developed by Onxeo, and is co-developed and marketed by Spectrum Pharmaceuticals in the United States.

The drug has received accelerated approval status from the U.S. Food and Drug Administration (FDA), meaning that Spectrum can market Beleodaq but that the approval is conditioned upon completion of further clinical trials.

It is also now being investigated as a treatment for other types of aggressive non-Hodgkin lymphomas (aNHL) including diffuse large B-cell lymphomas (DLBCL), as well as solid tumors such as non-small cell lung cancer (NSCLC).

How Beleodaq works

Lymphoma is a type of blood cancer in which lymphocyte cells multiply uncontrollably, travel around the body and amass to form tumors. There are many types of lymphoma, based on the type of lymphocyte affected and the progression of the disease.

It is a histone deacetylase inhibitor (HDACi) or enzyme with a wide range of functions. For instance, they help control what genes are expressed from the DNA of a cell, by modifying a protein that can alter how accessible the DNA is. HDACs also modify other essential proteins, including signaling proteins and DNA repair proteins.

The exact mechanism of action in cancer treatment is unknown. However, it is thought that by blocking the HDACs from working, Beleodaq can stop cancer cells from growing and kill them. While Beleodaq can also act on healthy cells, the drug preferentially targets cancerous cells first.

Beleodaq in clinical trials

The FDA approved Beleodaq for marketing in July 2014, based on the results of a key Phase 2 clinical trial (NCT00865969) called BELIEF. This was an open-label study aiming to test the efficacy and safety of Beleodaq in 129 patients with PTCL who tried at least one prior therapy. Patients received Beleodaq once daily injected into the bloodstream over 30 minutes, on days 1-5 every three weeks, until cancer progression or treatment-related toxicities.

The results, published in the Journal of Clinical Oncology, demonstrated that it had an overall response rate of 26 to 28 percent. This was slightly higher than previous treatments at 25 to 27 percent. On average, patients took 5.6 weeks to respond to Beleodaq, and the median duration of response was 8.3 months.

Unlike most other HDACi drugs, patients with low platelet count given Beleodaq still had an overall response rate of 15 percent. Beleodaq is the only FDA-approved drug that has been investigated with PTCL patients with platelet counts of less than 100,000/µL.

A Phase 1 trial (NCT01839097) investigating the maximum tolerated dose of Beleodaq in combination with CHOP therapy has been completed. Its results, presented at the 57th American Society of Hematology Annual Meeting and Exposition, showed an overall response rate of 86 percent to Beleodaq and CHOP combination, with 67 percent of patients achieving a complete response where the signs of cancers disappeared.

An ongoing exploratory Phase 2 trial (NCT01686165) is investigating the effect of Beleodaq in combination with Zevalin in five patients with aNHL. The results, recently published in the scientific journal Oncology, were not positive as the disease progressed in all patients following treatment.

Beleodaq, alone and in combination with other drugs, is being investigated in several ongoing clinical trials for lymphoma.

The drug’s continued approval will be based on the results of further Phase 3 clinical trials and testing of Beleodaq dosage in combination with CHOP therapy.

Other information

It can cause several side effects, the most common of which include nausea, fatigue, fever, anemia, vomiting, constipation, diarrhea, and difficulty breathing. For the full list of warnings, see the prescribing information.

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