Bayer Receives FDA Breakthrough Therapy Designation for PI3K Inhibitor Aliqopa™ (copanlisib) in Relapsed Marginal Zone Lymphoma

Today, Bayer announced that its anticancer drug Aliqopa (copanlisib) has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed marginal zone lymphoma (MZL) who have previously undergone two prior therapies.

According to statistics from the World Cancer Research Fund (WCRF), non-Hodgkin lymphoma (NHL) is the most common blood cancer worldwide, accounting for 3% of all cancer cases. The American Cancer Society estimated that in 2019, more than 74,000 people would be diagnosed with NHL, and approximately 20,000 would die from the disease.

Indolent non-Hodgkin lymphoma (iNHL) is a subtype of NHL characterized by slow progression and spread. The two most common forms of iNHL are follicular lymphoma (FL) and marginal zone lymphoma (MZL), accounting for 20% and 10% of all NHL cases, respectively. Although patients with NHL often respond well to initial treatment, their disease course is typically marked by multiple relapses, with each subsequent remission becoming progressively shorter. Patients with advanced-stage NHL usually require systemic chemoimmunotherapy and urgently need new, effective therapies to control the disease and prolong survival.

Aliqopa, developed by Bayer, is an intravenous phosphatidylinositol-3-kinase (PI3K) inhibitor. Preclinical studies have demonstrated that Aliqopa inhibits the PI3K-α and PI3K-δ kinase isoforms, which are predominantly expressed in malignant B cells, at sub-nanomolar concentrations. The PI3K signaling pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation can readily lead to non-Hodgkin lymphoma (NHL). Aliqopa induces tumor cell death and inhibits the proliferation of primary malignant B cells.

Aliqopa inhibits several key cellular signaling pathways, including B-cell receptor (BCR) signal transduction, CXCR12-mediated chemotaxis of malignant B cells, and NF-κB signaling in lymphoma cell lines. Aliqopa received orphan drug designation from the FDA for the treatment of follicular lymphoma (FL) and marginal zone lymphoma (MZL) in 2015 and 2017, respectively. In September 2017, it received accelerated approval for the treatment of adult patients with relapsed FL who have received at least two prior systemic therapies.

▲Mechanism of Action of Aliqopa: Dual inhibition of the PI3K-α and PI3K-δ kinase isoforms, blocking signal transduction (Image source: Aliqopa official website)

This Breakthrough Therapy Designation was granted based on the positive results from the Phase 2 CHRONOS-1 trial. Preliminary analysis of the results showed that the overall response rate (ORR) was 69.6% in the MZL subgroup who had previously received at least two prior therapies, while the ORR for the entire iNHL population was 59.2%.

Dr. Scott Z. Fields, Senior Vice President of Bayer’s Pharmaceutical Division and Head of Oncology Development, stated, “Clinical data indicate that Aliqopa may offer a new therapeutic option for patients with relapsed marginal zone lymphoma (MZL) who have unmet medical needs. Bayer looks forward to working closely with the FDA to make Aliqopa available to MZL patients as soon as possible.”

References:

[1]. Bayer Receives U.S. FDA Breakthrough Therapy Designation for Aliqopa™ (copanlisib) for the Treatment of Marginal Zone Lymphoma. Retrieved May，29, 2019, from https://www.biospace.com/article/releases/bayer-receives-u-s-fda-breakthrough-therapy-designation-for-aliqopa-copanlisib-for-the-treatment-of-marginal-zone-lymphoma/

[2]. Flash News | Bayer’s New Anti-Cancer Drug Receives FDA Priority Review Designation. Retrieved May 29, 2019, from https://mp.weixin.qq.com/s/wXQcYvesiyrtZbvx1OccNA

[3]. The 10th anticancer drug launched in 2017! Bayer’s new drug receives accelerated approval from the U.S. FDA today. Retrieved May 29, 2019, from https://mp.weixin.qq.com/s/psv0ziEDDnBKbsEXPc-suA

[4]. Nature In-Depth Review: Which Innovative Therapies Are Worth Watching for the Most Common Blood Cancers? Retrieved May 29, 2019, from https://mp.weixin.qq.com/s/GOE95oHepFjKi6KHQGKQew

[5]. Flash News: FDA Grants Breakthrough Therapy Designation to Lymphoma Therapy with Specific PI3K Isoform Targeting. Retrieved May 29, 2019, from https://mp.weixin.qq.com/s/RGaDaCugOIYqElFY5tsJYQ

Original Title: Express | Bayer's PI3K Inhibitor Receives FDA Breakthrough Therapy Designation for Lymphoma Treatment

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