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Phase 1 Trial Of All-Oral Ricolinostat-Revlimid-Dexamethasone Combo Begins – Acetylon Pharmaceuticals announced last week the initiation of a Phase 1b clinical trial of ricolinostat (ACY-1215) in combination with Revlimid (lenalidomide) and dexamethasone (Decadron) for the treatment of patients with relapsed or refractory multiple myeloma. Ricolinostat is an oral treatment that belongs to a family of anti-cancer drugs called HDAC inhibitors. Other HDAC inhibitors under investigation for multiple myeloma include Zolinza (vorinostat) and panobinostat. Acetylon believes that ricolinostat could produce fewer side effects than other non-specific HDAC inhibitors, as it selectively inhibits the enzyme HDAC6. The primary aim of the trial is to establish an optimal dose of ricolinostat over a 28-day treatment cycle and to assess the potential anti-myeloma activity of the three-drug combination. In addition, Acetylon is enrolling patients for a Phase 1/2 trial of ricolinostat in combination with Velcade (bortezomib) and dexamethasone in patients with relapsed or refractory myeloma. For more information on both trials, please see the Acetylon press release and the U.S. clinical trial registry.

Lucatumumab Shows Modest Activity As Single Agent In Relapsed/Refractory Myeloma – Results from a recent Phase 1 study indicate that lucatumumab, an antibody developed by Novartis, is well tolerated in relapsed or refractory myeloma patients; however, the compound only showed modest activity in the study participants. Specifically, 4 percent of patients maintained a partial response for a period of eight months or longer, and 43 percent maintained stable disease. The most common severe side effects included anemia (7 percent), chills (7 percent), and fever (7 percent). Side effects severe enough to limit drug dosage were seen in about 10 percent of patients. Based on these results, the researchers recommend that lucatumumab be tested in combination with other anti-myeloma drugs. For more information, please see the study in the British Journal of Hematology (abstract).

Viracept-Velcade Combo Kills Myeloma Cells Better Than Either Drug Alone – Researchers at the National Cancer Institute have found that a combination of the anti-HIV drug Viracept (nelfinavir) and Velcade kills myeloma cells better than either drug alone in a preclinical study. Viracept belongs to a class of drugs called protease inhibitors and was approved by the FDA to treat HIV in 1997. Both Viracept and Velcade limit a cell’s ability to chop up and discard unwanted proteins. Simultaneous treatment with both drugs resulted in an accumulation of such unwanted proteins in the cell, eventually resulting in cell death. For more information, please refer to the study in Cell Death and Disease.

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OncoPep and Dana-Farber Sign License Agreement For Myeloma Vaccine Technology – The biotechnology company OncoPep has signed a license agreement with the Dana-Farber Cancer Institute in Boston to further develop and commercialize PVX-410, a potential vaccine-based treatment for multiple myeloma. PVX-410 has been shown to stimulate an immune response against myeloma cell lines. Researchers plan to conduct a Phase 1/2a study this year of PVX-410 in patients with smoldering multiple myeloma.  OncoPep also hopes to use the PVX-410 technology to develop additional cancer vaccines. For more information, please see the OncoPep press release (pdf).

Celgene Invests $15 Million In Acetylon Pharmaceuticals – Celgene, the company that markets the myeloma treatments Revlimid (lenalidomide) and thalidomide (Thalomid), announced last week that it will invest $15 million in Acetylon Pharmaceuticals. Acetylon is developing ACY-1215, a selective HDAC inhibitor being investigated in a Phase 1/2  clinical trial with relapsed/refractory multiple myeloma patients. Other HDAC inhibitors under investigation for multiple myeloma include Zolinza (vorinostat) and panobinostat. Acetylon hopes that ACY-1215, which is more selective than other HDAC inhibitors, will be more effective and have fewer side effects. For more information, please see the Acetylon press release.

Anti-Alcoholism Drug Antabuse May Be Active Against Myeloma – In a recent preclinical study, Italian researchers demonstrated that Antabuse (disulfiram), a drug approved by the U.S. Food and Drug Administration to treat chronic alcoholism, has anti-myeloma effect. Antabuse, alone or in combination with copper, killed myeloma cell lines and cells from 22 newly diagnosed and relapsed/refractory myeloma patients. According to the Italian researchers, Antabuse was comparable to standard chemotherapy in terms of its ability to kill myeloma cells, but it did not harm healthy blood cells. For more information, please see the study in the International Journal of Cancer (abstract).

Generic Zometa Recommended For Approval In Europe – Zoledronic Acid Actavis, a generic version of Zometa (zoledronic acid) from the company Actavis, has received a positive recommendation for approval in the European Union.  The committee that provides guidance to the European Medicines Agency (EMA) made the recommendation last week.  If approved, Zoledronic Acid Actavis, like Zometa, will be available for use in the prevention of skeletal events in persons with advanced cancers involving bone, and for the treatment of tumor-involved high calcium levels. For more information, see the EMA announcement (pdf).

Cyclophosphamide-Velcade-Dexamethasone Combination Is Effective In Patients With Amyloidosis – Two research studies were published last week showing that a combination regimen used in the treatment of myeloma -- cyclophosphamide (Cytoxan) in combination with Velcade (bortezomib) and dexamethasone (Decadron), often abbreviated CyBorD or VCD -- may be effective in the treatment of amyloidosis. Amyloidosis is a blood disorder that results in the abnormal accumulation of proteins in tissues and organs throughout the body.  An estimated 10 percent to 15 percent of myeloma patients also develop symptoms associated with amyloidosis (see related Beacon news). Stem cell transplantation is a standard treatment for amyloidosis patients who are eligible. One of the studies published last week was a retrospective study that showed that 94 percent of amyloidosis patients responded to CyBorD treatment, and 18 percent of patients who were initially ineligible for a stem cell transplant became eligible following the treatment. The second study also was a retrospective analysis.  It found that 81 percent of amyloidosis patients responded to CyBorD treatment, and researchers also observed a rapid improvement in patients’ organ function.  For more information, please see the first and second studies in the journal Blood (abstracts).

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The results of a recent Phase 2 clinical trial indicate that the new drug Istodax, administered alone, is unlikely to achieve a significant response rate in therapy-resistant multiple myeloma patients. However, the results indicate that that Istodax may help stabilize M-protein production, resolve high calcium levels, or reduce bone pain in some multiple myeloma patients.

Istodax (romidepsin) is a cyclic peptide that inhibits an enzyme in cancer cells known as histone deacetylase (HDAC). By inhibiting HDAC, Istodax disrupts the cell cycle and causes cancer cell death. Istodax is marketed by Celgene Corporation …