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Biomarker-Directed Trial for AML or MDS, Safety and Efficacy of BMN 270 for Hemophilia, and more

December 30, 2021


David Steensma, MD
Dana-Farber Cancer Institute

Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA (INSPIRE) (NCT02562443)

  • Study Design: Randomized, parallel-assignment, open-label safety/efficacy study
  • Study Start Date: October 2015
  • Estimated Study Completion Date: September 2018
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 225
  • Sponsor: Onconova Therapeutics, Inc.

Patients with myelodysplastic syndromes (MDS) for whom the hypomethylating agents (HMA) azacitidine or decitabine have a poor prognosis have limited treatment options. In a previous study, ONTIME, the multikinase inhibitor rigosertib did not improve survival, compared with conventional care, for patients for whom HMAs fail (median survival = 8.2 months for rigosertib vs. 5.9 months for supportive care with or without low-dose cytarabine). However, patients who were primary-refractory to HMAs seemed to fare better. The INSPIRE study has a similar design to the ONTIME trial but enriches for higher-risk patients with no or transient responses to HMAs.

A Biomarker-Directed Phase 2 Trial of SY-1425 in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome (NCT02807558)

  • Study Design: Open-label, single-group assignment, safety/efficacy study
  • Study Start Date: July 2016
  • Estimated Study Completion Date: March 2019
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 40
  • Sponsor: Syros Pharmaceuticals

While retinoids such as tretinoin are the backbone of treatment of patients with acute promyelocytic leukemia (APL), a subset of patients with non-APL acute myeloid leukemia (AML) or MDS will respond to treatment with retinoic acid derivatives. Tamibarotene is a retinoid analogue licensed for treatment of APL in Japan. In this study, patients who have a gene expression signature (RARA or IRF8 genes) that pre-clinical testing has suggested indicates a higher likelihood of response to tamibarotene will be eligible for treatment with this drug.


Alice Ma, MD
University of North Carolina School of Medicine

A Phase 1/2, Dose-Escalation Safety, Tolerability and Efficacy Study of BMN 270, an Adenovirus-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Patients With Severe Haemophilia A (NCT02576795)

  • Study Design: Open-label, single-group assignment safety/efficacy study
  • Study Start Date: August 2015
  • Estimated Study Completion Date: June 2021
  • Study Status: Participant recruitment suspended
  • Estimated Enrollment: 12
  • Sponsor: BioMarin Pharmaceutical, Inc.

Novel gene-based therapies for hemophilia A have lagged behind those for hemophilia B, in part due to the large size of the factor VIII gene (>8kB, compared with 1.4 kB for factor IX). Recently, the bleeding disorders community was pleasantly stunned by initial results from the phase I/II study of an adenovirus-associated virus vector (AAV)-mediated gene therapy (BMN 270) for hemophilia A sponsored by BioMarin Pharmaceuticals. These initial results, released to shareholders, showed initial promising results for two patients who had been treated at the highest vector particle dose, achieving initial factor VIII levels of 57 percent and 60 percent.

In March 2016, BMN 270 was granted orphan drug designation by the U.S. Food and Drug Administration for hemophilia A.

Recruitment has been temporarily suspended while the study sponsor and E.U. regulators discuss the trial prior to starting BMN 270 in the last three patients enrolled in the trial. Almost all pharmaceutical companies performing factor IX gene therapy trials are turning their sights on factor VIII as well, though these clinical trials are not yet open for recruitment. It is anticipated that the trial will begin again.


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