There has not been an effective, and safe, FDA approved drug for MDS (myelodysplastic syndrome) or AML (acute myeloid leukemia) since Vidaza in 2004 and Dacogen in 2006. This post will examine the competitive landscape of companies with the hope of meeting the unmet need for MDS and AML patients...
MDS
Array - ARRY-614 Low or intermediate risk-1 MDS
MEI - Pracinostat/Vidaza intermediate-2 or high risk, and refractory MDS
Mirati - Mocetinostat intermediate or high risk MDS
Onconova - Rigosertib various MDS
Sunesis - Vosaroxin intermediate-2 or high risk refractory MDS
AML
BioLine - BL-8040 relapsed or refractory AML
Boehringer Indelheim - Volasertib relapsed or refractory, front line elderly AML
Cyclacel - Sapacitibine/Dacogen combo front line elderly AML
MEI - Pracinostat/Vidaza front line elderly AML
Sunesis - Vosaroxin IV Front line elderly AML
MDS Brief
Array Biopharma was involved with their drug ARRY-614 for low or intermediate risk-1 MDS, but after a phase 1 trial, they had this in their company literature, "Array has no plans to invest internally at this time in ARRY-614".
Mirati Therapeutics and their drug Mocetinostat an oral HDAC inhibitor ran a phase 1/2 trial for MDS and AML patients in 2013. The results were not overly impressive with just 9% achieving a CR and median overall survival was 12.4 months. There is a phase 2 intermediate or high risk MDS listed trial as of December 2013, with the completion December 2015. The company is exploring a subset of patients and dosing in a phase 2 for MDS. So the trial is ongoing at a very slow pace as the company has used the term "exploring".
Onconova Focuses on MDS patients with their lead drug Rigosertib IV. In a phase 3 trial for high risk refractory victims, the trial achieved a median overall survival of 8.5 months, compared to 4.7 months best support care. They have been working on an oral Rigosertib for MDS groups of patients.
Sunesis Has their drug Vosaroxin IV single agent for intermediate-2 or high risk refractory MDS. There has been a phase 1/2 trial posted since November of 2013 Phase 1/2 Vosaroxim IV, single agent for intermediate-2, or high risk refractory MDS, but there has been no movement or mention from Sunesis of the progress of that trial.
MEI Pharma Is currently involved with two MDS trials for lead drug an HDAC inhibitor Pracinostat in combination with Vidaza. Front line MDS is fully enrolled, and refractory MDS is in progress. We should have an interim readout on the refractory MDS trial by end of 2014, and a complete readout in the Pracinostat / Vidaza combo front line previously untreated intermediate-2 or high risk MDS trial in the first quarter of 2015.
AML Brief
BioLineRX Located in Isreal is involved with relapsed or refractory AML patients with drug BL-8040 in a current phase 2 study. The drug is in combination with Cytarabine a chemotherapy product. The trial is expected to complete in June 2015. This company competes with Sunesis and Boehringer Indelheim refractory AML patients.
Boehringer Indelheim Located in Germany has Volasertib IV, as their main drug for refractory and frontline AML. This company has many phase 1 trials currently running in combination with low dose cytarabine or Vidaza. Current phase 3 trial Volasertib IV Frontline Elderly AML competes directly with Cyclacel, and MEI Pharma in front line elderly AML. The differentiating factor is an IV infusion plus low dose chemo (Dacogen) against oral availability. Median overall survival in a phase 2 elderly AML, N=42, was 8.0 months vs. 5.2 in the chemo arm, and the CR+CRi = 31%.
Cyclacel Currently has a phase 3 trial 90% complete using their lead drug Sapacitibine oral and Dacogen IV experimental arm, against comparator Dacogen control arm, for frontline elderly AML patients called SEAMLESS. This trial has a total of 485 patients and has been running for 3.2 years and is expected to complete in early 2015. This trial competes directly with MEI Pharma, Sunesis and their currently running phase 2 trial. Early results from SEAMLESS phase 1/2 pilot, pooled top line achieved, N=46, CR=22%, CR+PR+HI = 37%, with median overall survival of 8 months, 60 day mortality was 13%.
MEI Pharma Currently has oral Pracinostat in combination with subcutaneous Vidaza in front line elderly AML patients. The trial is being sponsored by MD Anderson. The latest interim results show N=14, CR+CRi = 57% with zero progression since August 1st, and seven others too early to evaluate. The plan is for 40 patients total to be evaluated. MEI Pharma competes with Cyclacel and Sunesis for this indication. We may get a further update in December at ASH. The differential will be safety and overall survival with all three companies as the trials progress.
Sunesis Is currently in a phase 1/2 trial with lead drug (Vosaroxin IV combo Dacogen IV) experimental and, Dacogen IV control arm for front line elderly AML. The interim results early on June 2nd at ASCO look good, with N=16, CR=56%, CRp=13%, CRi=13% for an ORR=81% with seven too early to evaluate. The most recent update as of November 3rd, N=34, CR=50%, CRp=17%, CRi=9% for an ORR=76% and a CR+CRi=59%, with a 14% mortality rate at week eight. This trial competes with Boehringer, Cyclacel and MEI Pharma. The abstract is below.
ASH 2014 Vosaroxin
Bottom Line: Some of these companies will be announcing trial results in the next few months, so having this information available is important. Currently, there is only one curative treatment for MDS - allogeneic hematopoietic stem cell transplant (HSCT). However, old age and poor general performance status classifies approximately 75% of patients as ineligible for this treatment. I think we will see at least two indications approved in the next few years from the list of companies above. Thank you for reading.
MDS
Array - ARRY-614 Low or intermediate risk-1 MDS
MEI - Pracinostat/Vidaza intermediate-2 or high risk, and refractory MDS
Mirati - Mocetinostat intermediate or high risk MDS
Onconova - Rigosertib various MDS
Sunesis - Vosaroxin intermediate-2 or high risk refractory MDS
AML
BioLine - BL-8040 relapsed or refractory AML
Boehringer Indelheim - Volasertib relapsed or refractory, front line elderly AML
Cyclacel - Sapacitibine/Dacogen combo front line elderly AML
MEI - Pracinostat/Vidaza front line elderly AML
Sunesis - Vosaroxin IV Front line elderly AML
MDS Brief
Array Biopharma was involved with their drug ARRY-614 for low or intermediate risk-1 MDS, but after a phase 1 trial, they had this in their company literature, "Array has no plans to invest internally at this time in ARRY-614".
Mirati Therapeutics and their drug Mocetinostat an oral HDAC inhibitor ran a phase 1/2 trial for MDS and AML patients in 2013. The results were not overly impressive with just 9% achieving a CR and median overall survival was 12.4 months. There is a phase 2 intermediate or high risk MDS listed trial as of December 2013, with the completion December 2015. The company is exploring a subset of patients and dosing in a phase 2 for MDS. So the trial is ongoing at a very slow pace as the company has used the term "exploring".
Onconova Focuses on MDS patients with their lead drug Rigosertib IV. In a phase 3 trial for high risk refractory victims, the trial achieved a median overall survival of 8.5 months, compared to 4.7 months best support care. They have been working on an oral Rigosertib for MDS groups of patients.
Sunesis Has their drug Vosaroxin IV single agent for intermediate-2 or high risk refractory MDS. There has been a phase 1/2 trial posted since November of 2013 Phase 1/2 Vosaroxim IV, single agent for intermediate-2, or high risk refractory MDS, but there has been no movement or mention from Sunesis of the progress of that trial.
MEI Pharma Is currently involved with two MDS trials for lead drug an HDAC inhibitor Pracinostat in combination with Vidaza. Front line MDS is fully enrolled, and refractory MDS is in progress. We should have an interim readout on the refractory MDS trial by end of 2014, and a complete readout in the Pracinostat / Vidaza combo front line previously untreated intermediate-2 or high risk MDS trial in the first quarter of 2015.
AML Brief
BioLineRX Located in Isreal is involved with relapsed or refractory AML patients with drug BL-8040 in a current phase 2 study. The drug is in combination with Cytarabine a chemotherapy product. The trial is expected to complete in June 2015. This company competes with Sunesis and Boehringer Indelheim refractory AML patients.
Boehringer Indelheim Located in Germany has Volasertib IV, as their main drug for refractory and frontline AML. This company has many phase 1 trials currently running in combination with low dose cytarabine or Vidaza. Current phase 3 trial Volasertib IV Frontline Elderly AML competes directly with Cyclacel, and MEI Pharma in front line elderly AML. The differentiating factor is an IV infusion plus low dose chemo (Dacogen) against oral availability. Median overall survival in a phase 2 elderly AML, N=42, was 8.0 months vs. 5.2 in the chemo arm, and the CR+CRi = 31%.
Cyclacel Currently has a phase 3 trial 90% complete using their lead drug Sapacitibine oral and Dacogen IV experimental arm, against comparator Dacogen control arm, for frontline elderly AML patients called SEAMLESS. This trial has a total of 485 patients and has been running for 3.2 years and is expected to complete in early 2015. This trial competes directly with MEI Pharma, Sunesis and their currently running phase 2 trial. Early results from SEAMLESS phase 1/2 pilot, pooled top line achieved, N=46, CR=22%, CR+PR+HI = 37%, with median overall survival of 8 months, 60 day mortality was 13%.
MEI Pharma Currently has oral Pracinostat in combination with subcutaneous Vidaza in front line elderly AML patients. The trial is being sponsored by MD Anderson. The latest interim results show N=14, CR+CRi = 57% with zero progression since August 1st, and seven others too early to evaluate. The plan is for 40 patients total to be evaluated. MEI Pharma competes with Cyclacel and Sunesis for this indication. We may get a further update in December at ASH. The differential will be safety and overall survival with all three companies as the trials progress.
Sunesis Is currently in a phase 1/2 trial with lead drug (Vosaroxin IV combo Dacogen IV) experimental and, Dacogen IV control arm for front line elderly AML. The interim results early on June 2nd at ASCO look good, with N=16, CR=56%, CRp=13%, CRi=13% for an ORR=81% with seven too early to evaluate. The most recent update as of November 3rd, N=34, CR=50%, CRp=17%, CRi=9% for an ORR=76% and a CR+CRi=59%, with a 14% mortality rate at week eight. This trial competes with Boehringer, Cyclacel and MEI Pharma. The abstract is below.
ASH 2014 Vosaroxin
Bottom Line: Some of these companies will be announcing trial results in the next few months, so having this information available is important. Currently, there is only one curative treatment for MDS - allogeneic hematopoietic stem cell transplant (HSCT). However, old age and poor general performance status classifies approximately 75% of patients as ineligible for this treatment. I think we will see at least two indications approved in the next few years from the list of companies above. Thank you for reading.
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