May is an extremely busy month on the FDA's new drug review calendar. Many new drugs and new indications are about to reach their target action dates and are facing final approval decisions.

Heron Therapeutics: New drug HTX-011 for postoperative pain

The target date of action for the New Drug Application Application (NDA) of HTX-011 for the treatment of postoperative pain is May 12, 2021. The application was resubmitted on November 13, 2020. Heron held a Class A End-of-Review meeting with the US FDA in September 2020. The meeting aimed to clarify that the agency had targeted HTX-011 in June 2020. Questions raised in the issued complete response letter (CRL). The CRL stated that the U.S. FDA was unable to approve the NDA of the drug at that time and needed more non-clinical information. There are four non-clinical issues, three of which are related to pre-clinical reproductive toxicology studies, and the fourth issue is related to changes in manufacturing release specifications based on animal toxicology studies that allow impurity levels.

HTX-011 is a non-opioid analgesic, a dual-acting, fixed-dose combination of local anesthetic bupivacaine and low-dose non-steroidal anti-inflammatory meloxicam. In a phase 3 clinical study, HTX-011 significantly reduced patient pain and opioid use within 72 hours compared with bupivacaine solution. Bupivacaine is a nursing local anesthetic for postoperative pain control.

In September 2020, the European Commission (EC) granted HTX-011 a drug marketing authorization under the Zynelef brand for the use of somatic postoperative pain in adult small and medium surgical wounds.

Apellis Pharma: Paroxysmal nocturnal hemoglobinuria (PNH) drug Pegcetacoplan

The Apellis drug’s target action date is May 14 for the treatment of PNH, a rare blood disease that causes red blood cells to divide (hemolysis). Pegcetacoplan is a targeted C3 therapy designed to regulate the excessive activation of the complement cascade, which is part of the immune system. The drug is a synthetic cyclic peptide combined with polyethylene glycol polymer, which specifically binds to C3 and C3b.

On December 10, 2020, Apellis and Sweden’s SOBIO Biovitrum AB announced the positive top-line results for the 48th week of the Phase 3 clinical study Pegasus. The trial showed that PNH patients treated with Pegcetacoplan continued to improve in hematology and clinical practice. The safety profile is also consistent with previously reported data.

Sanofi: A new drug for Pompe disease (Avalglucosidase Alfa)

Sanofi's new drug has a biological preparation license application (BLA) target date of May 18 for long-term enzyme replacement therapy for patients with Pompe disease. The drug is designed to improve the delivery of acid alpha-glucosidase (GAA) to muscle cells. Pompe disease is an enzyme deficiency, a rare degenerative muscle disease that affects the patient's ability to move and breathe.

In early February 2021, at the 17th WORLDSymposium conference, Sanofi released data supporting the BLA. The drug also received breakthrough treatment and fast track designation from the US FDA.

Bristol-Myers Squibb (BMS): Opdivo adjuvant treatment of esophageal cancer or gastroesophageal junction cancer

The target date of action for BMS is May 20. It supplements BLA for Opdivo (nivolumab) in the treatment of neoadjuvant chemoradiotherapy (CRT) after adjuvant treatment of patients with resection of the esophagus or gastroesophageal junction (GEJ) cancer. The application for this indication has been prioritized for review.

This application is based on the positive results of the Phase 3 clinical trial CheckMate-577. The results showed that Opdivo reached its primary endpoint in disease-free survival (DFS) in patients with esophageal or GEJ cancer who had undergone CRT and tumor resection.

ADC Therapeutics: new drug Lonca for diffuse B-cell lymphoma

The BLA target action date for Lonca (loncastuximab tesirine) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is May 21. The application is based on data from the study of LOTIS 2, which is a pivotal phase 2 clinical trial of the drug for patients with relapsed or refractory DLBCL who have previously received two or more treatments. Lonca is an antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody against human CD19 and bound to pyrrolobenzazepine (PBD) dimer cytotoxin through a molecular linker. In this trial, Lonca showed an overall effective rate (ORR) of 48.3%, exceeding the target primary endpoint.

The US FDA approved Lonca on April 23, 2021 for patients with r/r large C-cell lymphoma who have received two or more systemic treatments, including DLBCL, non-other specific lymphoma (NOS), and DLBCL caused by low-grade lymphoma, and high-grade B-cell lymphoma. On May 5, ADC announced that ZYNLONTA™ (loncastuximab tesirine-lpyl) has been included in the latest National Comprehensive Cancer Network Clinical Practice Guidelines (NCCN Guidelines) for B-cell lymphoma oncology recommendations.

Reference source: FDA Action Alert: Heron, Apellis, Sanofi, Merck and ADC