MacroGenics Announces Registration Study of Flotetuzumab in Patients with Refractory Acute Myeloid Leukemia

Rhea-AI Summary

MacroGenics (NASDAQ: MGNX) announced plans for a pivotal clinical study of flotetuzumab, a bispecific DART molecule targeting CD123 and CD3, aimed at treating acute myeloid leukemia (AML) patients who are refractory to induction therapy. Following recent discussions with the FDA, the single-arm study will enroll up to 200 patients with primary induction failure or early relapse AML. Primary endpoints include complete remission rates, with secondary endpoints assessing response durability. Previous data showed a 27% CR/CRh rate in a smaller trial, indicating potential therapeutic value for a serious unmet medical need.

Positive

• Initiation of pivotal study for flotetuzumab, addressing significant unmet need in AML treatment.
• 27% complete remission (CR) or CR with partial hematological recovery (CRh) rate observed in earlier trials.

Negative

• Limited treatment options for refractory AML patients may indicate high competition and challenges in achieving significant market share.
• Concerns regarding the overall efficacy and safety profile based on prior adverse events like infusion reactions, which may affect trial outcomes.

Rockville, MD, May 27, 2020 (GLOBE NEWSWIRE) --

MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced plans for a clinical study intended to support registration in the U.S. of flotetuzumab, an investigational, bispecific CD123 x CD3 DART® molecule for patients with acute myeloid leukemia (AML) who are refractory to induction therapy.

Informed by recent discussions with the U.S. Food and Drug Administration (FDA), the Company plans a single-arm, registration-enabling clinical study to evaluate flotetuzumab in up to 200 patients with primary induction failure (PIF) or early relapse (ER) AML. The study will be conducted as a continuation of the ongoing Phase 1/2 study (NCT02152956; to be updated). Complete remission (CR) and CR with partial hematological recovery (CRh) will be the primary endpoint of the pivotal study. Key secondary endpoints will include durability of response and other supportive clinical endpoints.

“Patients with AML who are refractory to induction therapy or relapse early after an initial response have limited treatment options,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. “Clinical and translational data suggest that such refractory AML patients may be responsive to immunotherapy with flotetuzumab. We are very pleased to advance our first DART molecule into a pivotal study with an opportunity to address a significant unmet need.”

Data from the Phase 1/2 clinical study of flotetuzumab in patients with PIF/ER AML were presented in December 2019 at the American Society of Hematology (ASH) Annual Meeting. A CR/CRh rate of 27% (8 of 30) was observed in the intent-to-treat population. The most common treatment-related adverse event was infusion-related reaction/cytokine release syndrome that occurred in all patients and was mostly of short duration and mild to moderate (grade 1 or 2) in severity.

About Acute Myeloid Leukemia

AML is a hematological malignancy characterized by differentiation arrest and uncontrolled clonal proliferation of neoplastic precursors that prevent normal bone marrow hematopoiesis. Nearly 20,000 new cases of AML are diagnosed in the U.S. each year, with a median age of 69 years at diagnosis. Approximately 40-50% of newly diagnosed patients fail to achieve a complete remission with intensive induction therapy (primary induction failure) or experience disease recurrence after a short remission duration (<6 months; early relapsed). A very small number of these patients are expected to respond to salvage therapy. Although new targeted agents have been approved for the treatment of frontline or relapsed/refractory AML in recent years, approximately 50% of patients have no known targetable mutations.

About Flotetuzumab

Flotetuzumab (also known as MGD006) is a clinical-stage bispecific DART molecule that recognizes both CD123 and CD3. CD123, the interleukin-3 receptor alpha chain, has been reported to be over-expressed on malignant cells in AML and other hematologic malignancies. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cells. The FDA has granted orphan drug designation to flotetuzumab for the treatment of AML.

About MacroGenics, Inc.

MacroGenics is a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company's website at www.macrogenics.com. MacroGenics, the MacroGenics logo and DART are trademarks or registered trademarks of MacroGenics, Inc.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company's strategy, future operations, clinical development of the Company's therapeutic candidates, milestone or opt-in payments from the Company's collaborators, the Company's anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words "subject to", "believe", "anticipate", "plan", "expect", "intend", "estimate", "project", "may", "will", "should", "would", "could", "can", the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners and other matters that could affect the availability or commercial potential of the Company's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the novel coronavirus (referred to as COVID-19), and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof.

Anna Krassowska, Ph.D., Vice President, Investor Relations & Corporate Communications
Jim Karrels, Senior Vice President, CFO
1-301-251-5172, info@macrogenics.com

FAQ

What is MacroGenics planning with flotetuzumab?

MacroGenics plans to initiate a pivotal clinical study for flotetuzumab, aimed at obtaining U.S. registration for treating acute myeloid leukemia.

What are the key endpoints of the flotetuzumab clinical study?

The primary endpoint is the complete remission rate, with secondary endpoints including durability of response and other supportive clinical measures.

How many patients will participate in the flotetuzumab study?

The study will evaluate up to 200 patients with primary induction failure or early relapse acute myeloid leukemia.

What was the outcome of previous clinical trials for flotetuzumab?

Previous trials reported a complete remission rate of 27% among the intent-to-treat population.

What challenges does MacroGenics face with flotetuzumab in AML treatment?

The company faces challenges due to limited treatment options for refractory AML and potential competition in the market.