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Potential New MDS Treatments: What Is On The Horizon?

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Published: Nov 7, 2012 11:16 am
Potential New MDS Treatments: What Is On The Horizon?

Two myelodysplastic syndromes (MDS) experts from the United Kingdom, Dr. Ghulam Mufti and Dr. Austin Kulasekararaj from King’s College Hospital in London, recently published a review of ongoing research into potential new MDS treatments.

The review describes a wide range of potential new MDS treatments.  For each therapy or group of therapies, the authors summarize the results of key clinical trials, and they also describe how the therapies are believed to act against MDS.

In addition, the review includes the  experts’ thoughts on where research into new treatments should go in the future.

The experts begin their review by noting that significant advances in the treatment of MDS have been made during the last decade with the approval of Vidaza (azacitidine), Revlimid (lenalidomide), and Dacogen (decitabine).

In addition, progress has been made in understanding the evolution and progression of MDS.  This progress aids the development of new treatments and the refinement of existing therapies.

The authors hope that, eventually, a more thorough understanding of the molecular mechanisms of MDS will lead to personalized therapy for the disease, with MDS treatment being highly customized for each patient.

More than 200 clinical trials are currently ongoing for MDS-related treatments that do not involve stem cell transplantation.


Estybon (rigotersib) is an investigational drug that is being developed by the pharmaceutical company Onconova Therapeutics.  It works by inhibiting cell growth and selectively killing cancer cells.

According to the authors of the review, several Phase 1/2 studies have studied the efficacy and safety of Estybon in MDS and acute myeloid leukemia (AML).

In one of the trials involving high-risk MDS patients who failed previous treatment with Vidaza or Dacogen, Estybon showed encouraging activity (see related Beacon news).

In another study in high-risk MDS patients and in AML patients with trisomy 8, Estybon decreased patients’ immature blood cell counts (see related Beacon news).

A third study investigated the use of a continuous infusion of Estybon over a period of 72 hours to 144 hours every two weeks. The investigators observed bone marrow responses in half of the study participants.

Based on these studies, the authors of the review conclude that further studies are warranted to better define the biologic activity of Estybon and the appropriate target population for the drug.


Tarceva (erlotinib) is an oral drug that is marketed in the United States by the biotechnology company Genentech. It has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-small cell lung cancer. It works by inhibiting cellular processes and causing cell death, and it has proven efficient at killing MDS cells in preclinical studies.

In a recent Phase 2 trial, 15 percent of MDS patients who had previously received Vidaza or Dacogen responded to Tarceva treatment. The overall survival was 6.8 months for all study participants and 16.5 months for patients who responded.

Tarceva also is being investigated in a Phase 1/2 study for high-risk MDS patients who are ineligible for, or have failed, intensive chemotherapy and treatment with Vidaza or Dacogen.


Telintra (ezatiostat hydrochloride) is an investigational drug being developed by the biopharmaceutical company Telik (NASDAQ: TELK) as a potential oral treatment for lower-risk MDS.  It stimulates the growth and maturation of developing blood cells and kills off cells that are unable to mature properly.

According to the authors of the review, intravenous Telintra has shown good efficacy and safety in two Phase 1/2 trials in MDS patients.

Based on these findings, a Phase 1 trial of oral Telintra has been launched. Initial results of the trial have shown that 38 percent of patients achieved an improvement in blood cell counts. The review authors point out that only mild to moderate side effects were observed.

Results from another Phase 2 clinical trial showed that extended dosing of orally administered Telintra improves blood cell counts and reduces dependence on red blood cell transfusions in patients with lower-risk MDS (see related Beacon news). According to the authors of the review, the side effect profile continued to be favorable.


Tosedostat, an investigational drug being developed by Cell Therapeutics (NASDAQ: CTIC), belongs to a new class of drugs called metalloenzyme inhibitors. It prevents enzymes in cancer cells that regulate growth from working properly, eventually leading to cell death.

According to the authors of the review, tosedostat showed good efficacy in a recent Phase 1/2 trial involving MDS patients; 14 percent of the patients achieved a complete response and an additional 14 percent achieved a partial response (see related Beacon news). The review authors note that tosedostat was well tolerated.

The authors also point out that combination therapies such as tosedostat plus Dacogen and tosedostat plus cytarabine are currently being evaluated in Phase 2 trials.


Siltuximab belongs to a broad class of drugs known as monoclonal antibodies. It blocks the activity of IL-6, a protein often found at elevated levels in patients with MDS. Siltuximab is being developed by Janssen Biotech, a Johnson & Johnson company (NYSE: JNJ), and has been investigated for the treatment of prostate cancer, ovarian cancer, metastatic renal cell cancer, multiple myeloma, and Castleman’s disease (the overgrowth of lymphatic cells).

According to the authors of the review, siltuximab is currently in a Phase 2 study that evaluates its efficacy as a treatment for anemia in MDS.

mTor Inhibitors

mTor inhibitors prevent the activity of “mammalian target of rapamycin” (mTor), a protein that is known to promote tumor cell growth. mTor inhibitors are already approved for a number of medical uses, but they only recently have been investigated as possible cancer treatments.

Afinitor (everolimus), which is approved by the FDA for the treatment of advanced kidney cancer, was investigated in a Phase 1 trial as a potential treatment for MDS. According to the authors of the review, however, Afinitor showed only modest activity in MDS.

Torisel (temsirolimus), another mTor inhibitor also approved by the FDA for use in advanced kidney cancer, is currently being tested in a Phase 1 trial as a potential treatment for MDS.

Hedgehog Pathway Inhibitors

Hedgehog pathway inhibitors are compounds that block the so-called hedgehog pathway, a process in the human body involved in the maintenance of stem cells.  Problems with the hedgehog pathway can lead to various blood-related cancers, including MDS.

The authors of the review point out that six compounds in this class of drugs are currently being investigated as potential treatments for blood-related cancers.

One of these compounds, PF-04449913, which is being developed by Pfizer (NYSE: PFE), has shown early signs of activity and a good safety profile in a Phase 1 trial involving patients with various blood-related cancers, including MDS.

MAPK Inhibitors

MDS is a condition characterized by an ineffective production of blood cells.  This, the review authors explain, is mainly due to increased cell death in the bone marrow. MAPK inhibitors are compounds that suppress the function of the protein MAPK, which has been associated with enhanced cell death.

SCIO-469, an investigational MAPK inhibitor developed by Scios Pharmaceuticals, has been shown to decrease cell death and increase the formation of blood cells.

In particular, results of a Phase1/2 trial in lower-risk MDS patients who failed to respond to red blood cell-stimulating agents showed that 40 percent of patients treated with SCIO-469 achieved an improvement in blood cell counts.

Another MAPK inhibitor, ARRY-614, which is being developed by Array BioPharma (NASDAQ: ARRY), showed activity as a single agent in a Phase 1 trial involving lower-risk MDS patients. At the highest administered dose, 38 percent of study participants responded to treatment. Across all patients, 30 percent of study participants showed improved blood cell counts.

Neddylation Inhibitors

Neddylation inhibitors are compounds that block the breakdown of proteins in cancer cells, thereby triggering their death.

The authors of the current review note that one investigational compound in this class of drugs, MLN4924, which is being developed by Millennium Pharmaceuticals, has shown remarkable activity in preclinical studies. The compound is currently being investigated in a Phase 1 trial for MDS and AML. Preliminary results of the trial showed that 20 percent of study participants achieved a complete response.

PARP Inhibitors

PARP inhibitors have primarily been investigated as potential treatments for certain kinds of breast cancers. However, one PARP inhibitor, BMN 673, which is being developed by BioMarin Pharmaceutical (NASDAQ: BMRN), is being investigated in a Phase 1 trial for the treatment of MDS, AML, chronic lymphocytic leukemia, and mantle cell lymphoma.

The researchers point out that PARP inhibitors increase the efficacy of conventional chemotherapy, in particular cyclophosphamide (Cytoxan), which indicates that the drugs could be used in combination therapy.

TGF-Beta Signaling Inhibitors

TGF-beta signaling inhibitors are compounds that block TGF-beta signaling, a process that affects many aspects of cell growth, differentiation, and death.

Previous research has shown that TGF-beta signaling activation may play a role in MDS. One investigational compound in this class of drugs — LY-2157299, which is being developed by Eli Lilly (NYSE: LLY) — may potentially reverse the activation process and therefore be useful as a treatment for MDS.

Other Compounds

The review authors also mention a few additional drugs under investigation as potential treatments for MDS. They include lintuzumab, vatalanib, aflibercept, AS-101, and SGI-110, which belongs to the same class of drugs as Vidaza and Dacogen.

For more information, please see the review in the journal Seminars of Hematology (abstract).

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  • Andy Lim said:

    I am a patient and keep me inform of the lastest news

  • Linda Vuong said:

    Hi Andy.

    You can sign up to receive emails with all the new articles the MDS Beacon publishes here: http://www.mdsbeacon.com/email-subscription/

    Best regards.

  • L.Chandi said:

    kindly keep me updated with all such info, it has to do with my family.

  • Maike Haehle (author) said:

    Dear L.Chandi, we have added you to our email subscriber list so you will be receiving an email every time we publish an article.