Is Ridaforolimus the Long Awaited Systemic Agent for Treatment of Sarcoma?

ridaforolimusRidaforolimus, CAS number 572924-54-0, is an immunosuppressant designed for the treatment of certain cancers. Formerly known as Deforolimus, ridaforolimus is a small-molecule inhibitor of the protein mTOR.  This protein acts as a central regulator of cell proliferation, cell cycle progression, protein synthesis and cell survival in cancer cells. By blocking the protein mTOR a starvation effect is created in cancer cells by interfering with their cell growth, metabolism, division and angiogenesis. Developed by both Merck and ARIAD Pharmaceuticals, ridaforolimus may also be known as AP23573 and MK-8669. LGM Pharma supplies ridaforolimus for R&D purposes, and offers assistance to clients through all stages of research.

The Phase 3 SUCCEED trial met the primary endpoint and demonstrated an improved progression-free survival compared with the placebo. The success of this trial was announced by ARIAD in January 2011, and included patients with metastatic soft-tissue and bone sarcomas, who had a favorable response to chemotherapy. Of the 711 patients participating there was a 28 percent reduction  in the risk of progression for patients who received ridaforolimus, versus a placebo.

“…the patient takes one 40 milligram dose only five days a week, with a two day a week drug “holiday””

Ridaforolimus is unique as a treatment for patients with cancer because it is administered orally, unlike the typical intravenous administration for cancer treatments. The dosage is also atypical compared to most cancer treatments, as the patient takes one 40 milligram dose only five days a week, with a two day a week drug “holiday”. This methodology has proven to be advantageous in the clinical outpatient setting, by offering better tolerability, increased efficacy and a convenient treatment schedule for many patients.

While the prognosis for patients with advanced or metastatic sarcoma is generally poor, ridaforolimus offers a ray of hope for this patient profile. There has not been a new systemic agent approved for use in soft-tissue or bone sarcoma within the United States for more than twenty years. If approved ridaforolimus would be the first targeted agent to be approved for this patient population.

Currently being investigated in multiple clinical studies, alone and in combination with other agents, developers of ridaforolimus anticipate approval. On October 5,2011 both Merck and ARIAD announced that the U.S. Food and Drug Administration (FDA) accepted for filing and review the New Drug Application (NDA) for ridaforolimus. In addition to treatment for sarcomas, ridaforolimus is also currently being investigated for treatment of other cancers, including breast, endometrial, prostate and non-small cell lung cancers.