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                Resources for Information | Approved Drugs

Resources for Information | Approved Drugs

                        Oncology (Cancer) / Hematologic Malignancies Approval Notifications
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          FDA D.I.S.C.O.: A new treatment for acute myelogenous leukemiaResources for Information | Approved Drugs FDA D.I.S.C.O.: A new treatment for acute myelogenous leukemia
  
  	
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*FDA medical oncologists discuss the Aug. 3, 2017, approval of Vyxeos for treatment of acute myelogenous leukemia.*

Sanjeeve Bala: Welcome back to the DISCO. Today’s Drug Information Soundcast in Clinical Oncology from FDA’s Oncology Center of Excellence discusses the recent approval of (daunorubicin and cytarabine) liposome for injection, marketed as Vyxeos.

Abhilasha Nair: Acute myelogenous leukemia remains an infrequent but life-threatening complication following cancer treatment with cytotoxic chemotherapy or radiation. Epidemiologic studies suggest that some inherited factors may play a role in the 8-10% of patients treated for primary malignancies that develop treatment-related AML around five years later. Today at the DISCO, we’ll discuss a recent approval for patients with newly-diagnosed treatment-related AML as well as AML with myelodysplasia-related changes, or AML-MRC, which represents an additional 20% of all AML. I’m Abhilasha Nair, an oncologist at FDA.

SB: And I am Sanjeeve Bala, also an oncologist at FDA. Patients with treatment-related AML have a poorer prognosis than those with de novo AML, as do those with AML-MRC. Standard approaches in patients who can tolerate intensive therapy include the 7+3 combination regimen of cytarabine and daunorubicin, and stem-cell transplantation. This approval represents FDA’s first for treatment specifically of these high-risk subtypes of AML, and is based on improved overall survival.

AN: An improvement in overall survival is a major step for patients with treatment-related AML. Tell us a bit about the background and mechanism of action of (daunorubicin and cytarabine) liposome for injection.

SB: Abhi, this drug is a nanoscale liposome-encapsulated combination of daunorubicin and cytarabine. They are present at a one to five molar ratio within the product, and research suggests that the ratio of these two cytotoxics at the target cells does impact their synergism and therefore their efficacy.

AN: So there isn’t actually a new cytotoxic drug in this approval. Tell us a bit about the approval pathway for these types of agents.

SB: This agent was approved through the 505(b)(2) pathway. This pathway is intended to minimize unnecessary duplication of clinical trials and make approvals more efficient. Products that are based on previously approved, or reference listed products, can use some safety and efficacy data from those older products. This pathway allows FDA to incorporate safety and efficacy data that were not collected in the current application.

AN: So in this case, the company had to perform clinical trials, but their application could reference additional safety and efficacy information from previously-approved daunorubicin and cytarabine data. Let’s discuss the pivotal trial for this approval, starting with the design.

SB: This liposomal product was evaluated in a clinical trial of 309 patients with newly-diagnosed treatment-related AML or AML with myelodysplasia-related changes. Patients ranged from 60 to 75 years of age. They were randomized 1 to 1 to first induction with the standard 7+3 regimen, where daunorubicin and cytarabine are given separately over three and seven days, respectively, or to first induction with (daunorubicin and cytarabine) liposome for injection given every other day for three infusions.

AN: With an aggressive disease like AML, where life expectancy is so short, I would expect that the trial endpoint was overall survival.

SB: Yes, that’s right, Abhi. Overall survival was the primary endpoint. Patients on the treatment arm had a median survival of 9.6 months, as compared with 6 months for patients treated with the standard of care. While this is a significant improvement in survival for patients with a terrible malignancy, we obviously have a long way to go.

AN: Tell us about the safety findings for the compound.

SB: Common side effects are similar to those seen with the traditional cytarabine and daunorubicin combination, including those related to the delayed recovery of marrow progenitors. Patients on the treatment arm had more bleeding events than those receiving standard treatment.

AN: That’s all related to the prolonged cytopenias that these patients develop as a result of their treatment, right?

SB: That’s correct. Additional toxicities that were more common in the (daunorubicin and cytarabine) liposome for injection group were rash, headache, and musculoskeletal pain. Notably, the company will be required to conduct a trial to better understand the rate of infusion-related reactions. An important safety consideration is that the newly approved agent is not interchangeable with cytarabine or daunorubicin in any form, and the package insert contains a boxed warning to this effect, along with more detailed safety information.

AN: Give us the three take-home points from this DISCO.

SB: (Daunorubicin and cytarabine) liposome for injection represents the first approval based on improved overall survival for treatment-related AML as well as AML-MRC. The compound represents a new nanoscale formulation of daunorubicin and cytarabine. And the toxicity profile appears similar to the standard 7+3 but with an increased incidence of bleeding. Detailed prescribing and safety information may be found in the package insert available on the web at Drugs@FDA.

SB: For a transcript with links to an in-depth look at the FDA analysis, and the multidisciplinary team of FDA experts who conducted the review, visit the FDA Oncology Center of Excellence DISCO website at fda.gov/DISCO.

AN: Are there other FDA oncology approvals that you would like to hear about? Leave us your questions and comments on Twitter @FDAOncology. I’m Abhi Nair, and thank you for tuning in.

SB: And until next time at the DISCO, I’m Sanjeeve Bala.

**Acknowledgements:**

This Drug Information Soundcast in Clinical Oncology was developed by Abhilasha Nair, Sanjeeve Bala, Aviva C. Krauss, Kirsten B. Goldberg, and Richard Pazdur, of the Oncology Center of Excellence and the Office of Hematology and Oncology Products. Steven Jackson of the Division of Drug Information was the sound producer.

Members of the Multi-Disciplinary Review and Evaluation team for this product application were:

Biometrics: Xin Gao
Biopharmaceutics: Gerlie Gieser
Clinical: Aviva C. Krauss
Clinical Pharmacology: Liang Li
Epidemiology: Carolyn A. McCloskey
Medication Error: Nicole B. Garrison
Non-Clinical: Michael L. Manning,
OSE Regulatory Project Manager: Neil Vora
Pharmacovigilance: Shital H. Patel
Pharmacovigilance: Connie N. Cheng
Regulatory Project Manager: Wanda D. Nguyen

                                                                                  Content current as of:
      09/15/2017
              
              
Regulated Product(s)
		 Drugs
			  			     			  						              
			
			
			
			
						  OncologyResources for Information | Approved Drugs

          
                        Oncology (Cancer) / Hematologic Malignancies Approval Notifications
          Ongoing | Cancer Accelerated Approvals
          Verified Clinical Benefit | Cancer Accelerated Approvals
          Withdrawn | Cancer Accelerated Approvals
          Other | Cancer Accelerated Approvals


                        Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description
 
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