Background Analysis: US FDA Advisory Committee to Review Amgen’s Blincyto for Minimal Residual Disease-Positive B-cell Precursor Acute Lymphoblastic Leukemia – MAR 7, 2018 (ODAC)

Announcement

The US FDA has scheduled a half-day meeting of the Oncologic Drugs Advisory Committee (ODAC) for Wednesday, March 7, 2018 to discuss a supplemental biologics license application (sBLA) for Blincyto (blinatumomab) injection for intravenous (IV) use, which was submitted by Amgen, Inc. (Amgen). The proposed indication is the treatment of minimal residual disease-positive B-cell precursor acute lymphoblastic leukemia (ALL).

Indication Background

Description of Indication

Acute lymphoblastic leukemia (ALL) is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes. The disease progresses quickly and is the most common childhood cancer in the US. The National Cancer Institute (NCI) estimates that approximately 3,100 patients aged 20 and younger are diagnosed with ALL each year. ALL can be of either T- or B-cell origin, with B-cell being the most common.

The proposed indication for Blincyto is for the treatment of minimal residual disease (MRD) positive B-cell precursor ALL. MRD refers to the presence of a small amount of detectible cancer cells that remain in the patient after treatment. Persistent or recurrent MRD is thought to be a precursor of disease relapse.

Product Background

Description of Product

Blincyto is a monoclonal antibody that is already FDA-approved for the treatment of relapsed or refractory B-cell precursor ALL in adults and children. Its mechanism of action is the activation of endogenous T cells by connecting CD3 in the T-cell receptor complex with CD19 on benign and malignant B cells. The product carries a Boxed Warning for cytokine release syndrome and neurological toxicities.

Clinical Trials of Proposed Indication

The sBLA is based on the Phase 2 BLAST study (ClinicalTrials.Gov ID: NCT01207388) that evaluated adult patients with B-cell precursor ALL and persistent or recurrent MRD after at least three cycles of intensive chemotherapy. Patients received continuous IV infusion of 15 μg/m2/d for four weeks, followed by two weeks off. Patients received up to four cycles of treatment, or could undergo a hematopoietic stem cell transplantation at any time after the first cycle, if eligible.

The primary endpoint was the rate of complete MRD response within the first treatment cycle. The key secondary endpoint was relapse-free survival at 18 months. Additional secondary endpoints included incidence and severity of adverse events, overall survival, time to hematological remission, and duration of complete MRD response.

The study results were published in the journal Blood in January 2018. The abstract stated (in part):

Eighty-eight of 113 evaluable patients (78%) achieved a complete MRD response. In the subgroup of 110 patients with Philadelphia-chromosome negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 53%. Median overall survival was 36.5 months. In a landmark analysis, complete MRD responders had longer relapse-free survival (23.6 vs 5.7 months; P=0.002) and overall survival (OS) (38.9 vs 12.5 months; P=0.002) compared with MRD nonresponders.

Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) patients and three (3%) patients had grade 3 or 4 neurologic events, respectively. Four (3%) patients had cytokine release syndrome (two grade 1 and two grade 3), all during cycle 1. Following treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, the majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders.

Regulatory Background

US Regulatory Background

March 29, 2018 – PDUFA date

unknown – Submission date of sBLA 125557/S-013

Breakthrough Therapy Designation, Priority Review

Ex-US Regulatory Background

November 2015– Blincyto was granted conditional marketing authorization in the European Union for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. Amgen says that additional regulatory applications for Blincyto are underway and have been submitted to health authorities worldwide.

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to the FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA and the Sponsor’s briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: Amgen, Inc. Drug Name: blinatumomab Drug Class: CD19-directed CD3 T-cell engager Indication: acute lymphoblastic leukemia

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DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.