Onrigin™ (laromustine)

Onrigin™ (laromustine), formerly Cloretazine® (VNP40101M) is a novel alkylating agent that is being evaluated for the treatment of acute myeloid leukemia (AML) in a pivotal Phase 2 trial in elderly de novo poor-risk AML. In addition, three clinical trials of Onrigin™ (laromustine) are underway in: (i) elderly AML and myelodysplastic syndromes in combination with cytarabine; (ii) brain tumors in combination with temozolomide; and (iii) advanced hematologic malignancies in combination with hematopoietic cell transplantation.

Q. What is Onrigin™ (laromustine) and how does it work?

A: Onrigin™ (laromustine) is a small molecule that works by damaging DNA. Onrigin™ (laromustine) releases the DNA chloroethylating agent 90CE after entering the blood stream. 90CE chloroethylates the O6 position of guanine residues, ultimately resulting in an interstrand DNA cross-link. Interstrand DNA cross-links are difficult to repair and are toxic to cells. Onrigin™ (laromustine) demonstrated a broad spectrum of anticancer activity in preclinical studies, including activity in selected cell lines resistant to other alkylating agents such as BCNU, cyclophosphamide and melphalan. In preclinical studies, Onrigin™ (laromustine) has been combined with other anticancer agents such as cytarabine (Ara-C). In addition, Onrigin™ (laromustine) or its metabolite, has been shown to be capable of crossing the blood brain barrier in preclinical models.

Q. In what clinical trials is Onrigin™ (laromustine) being evaluated?

A: Onrigin™ (laromustine) is being evaluated for the treatment of acute myeloid leukemia (AML) in a pivotal Phase 2 trial in elderly de novo poor-risk AML. In addition, four clinical trials of Onrigin™ (laromustine) are underway in: (i) AML and myelodysplastic syndrome (MDS) in combination with cytarabine; (ii) AML and MDS in combination with standard remission-induction therapy; (iii) brain tumors in combination with temozolomide; and (iv) advanced hematologic malignancies in combination with hematopoietic cell transplantation.

Below is a table with a list of all completed, closed and ongoing Onrigin™ (laromustine) clinical trials.

Trial

Indication

Sponsor

Commencement Date

Status

Phase III trial with standard remission-induction therapy

AML and MDS

Investigator

December 2008

Ongoing

Phase III trial in combination with Ara-C

AML, relapsed

Vion

March 2005

Clinical hold lifted by FDA; New Phase III trial in development

Phase II single agent trial

AML, elderly poor-risk

Vion

May 2006

Ongoing

Phase II single agent trial

Small cell lung cancer

Vion

September 2005

Closed

Phase II single agent trial

Brain tumors, adult

Investigator

June 2004

Completed

Phase II single agent trial

AML and high-risk myelodysplastic syndromes, elderly; AML, relapsed

Vion

March 2004

Completed

Phase I/II trial in combination with cytarabine

Elderly AML and MDS

Investigator

May 2008

Ongoing

Phase I/II trial in combination with temozolomide

Brain tumors, adult

Investigator

September 2007

Ongoing

Phase I/II single agent trial

Chronic lymphocytic leukemia

Vion

July 2005

Closed

Phase I trial in combination with stem cell transplantation

Hematologic malignancies

Investigator

November 2007

Ongoing

Phase I trial

Brain tumors, pediatric

Investigator

April 2005

Completed

Phase I trial in combination with temozolomide

Hematologic malignancies

Vion

October 2004

Completed

Phase I trial in combination with Ara-C

Hematologic malignancies

Vion

July 2003

Completed

Phase I single agent trial

Solid tumors

Vion

February 2003

Completed

Phase I single agent trial

Hematologic malignancies

Vion

August 2002

Completed

Phase I single agent trial

Solid tumors

Vion

June 2001

Completed