Ricolinostat (ACY-1215) is an investigational selective histone deacetylase (HDAC) inhibitor that was being developed by Acetylon Pharmaceuticals, which was later acquired by Celgene. Celgene is now part of Bristol-Myers Squibb (BMS).
The oral treatment is being investigated for myeloma in combination with dexamethasone and an immunomodulatory treatment such as Revlimid (lenalidomide), or a proteasome inhibitor such as Velcade (bortezomib).
How does ricolinostat work?
As an HDAC inhibitor, ricolinostat works by inhibiting the activity of the HDAC enzyme, which is required to “turn off” genes by removing the acetyl groups from histones, a group of proteins that are bound to DNA. Inhibiting the activity of the HDAC enzyme can “turn on” tumor suppressor genes to help control cell division and slow down cancer progression.
Ricolinostat specifically targets the HDAC 6 protein, an important protein that regulates the trafficking of misfolded proteins towards degradation. The inhibition of the activity of HDAC 6 by ricolinostat leads to the accumulation of these misfolded proteins inside myeloma cells. This accumulation is toxic for the cells and could result in the death of myeloma cells.
Ricolinostat in clinical trials
A Phase 1/2 clinical trial (NCT01323751) evaluated the effect of ricolinostat alone and in combination with Velcade and dexamethasone in 120 patients with relapsed or refractory multiple myeloma (RRMM), who have received at least two prior treatments. The trial was completed in December 2016 but no results have been published yet.
In another trial, researchers aimed to determine the maximum tolerated dose and dose schedule of ricolinostat in combination with Pomalyst (pomalidomide) and dexamethasone in 16 RRMM patients who have received at least two lines of prior therapy. The Phase 1b clinical trial (NCT02189343) was completed in 2018 but no results were published to date.
The most effective dose of ricolinostat, in combination with Revlimid and dexamethasone, was being sought in a Phase 1/2 interventional clinical trial (NCT01583283) trial involving 38 patients with RRMM, who have received at least one prior line of therapy. Although a maximum tolerated dose could not be determined, preliminary results showed that 160 mg of ricolinostat in combination with 25 mg of Revlimid and 40 mg of dexamethasone once daily for 28 days was well-tolerated with 21 patients showing a good overall response.
A Phase 1/2 clinical trial (NCT01997840) is evaluating the side effects and best dose of ricolinostat in combination with Pomalyst and dexamethasone in 101 RRMM patients who have received at least two lines of prior therapies. The trial is ongoing but no longer recruiting participants. It is expected to be completed in January 2021.
Other information
Ricolinostat is also being evaluated for the treatment of inflammatory breast cancer and peripheral neuropathies such as Charcot-Marie-Tooth disease.
Last updated: Feb. 26, 2020
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