FDA Action Alert: Athenex, Blueprint, CorMedix and More
The end of February and beginning of March is a busy time for the U.S. Food and Drug Administration (FDA), with a number of PDUFA dates on the calendar. Read on for more.
Athenex’s Oral Paclitaxel for Metastatic Breast Cancer
Athenex has a target action date of February 28, 2021, for its New Drug Application (NDA) for Oral Paclitaxel for metastatic breast cancer, under Priority Review. The submission was built on topline data released in August 2019 for its Phase III trial.
On December 9, 2020, the company presented updated Phase III progression-free survival (PFS) and overall survival (OS) data on the clinical benefits in efficacy and tolerability of oral paclitaxel versus intravenous paclitaxel (IVP) in patients with metastatic breast cancer. The median PFS data demonstrated a benefit for oral paclitaxel compared to IVP, 8.4 versus 7.4 months, respectively, and median OS data was 23.2 months compared to 16.3 months, respectively.
“The oral paclitaxel regimen appears to overcome some of the limitations of IV therapy, particularly in terms of reducing the risk of neuropathy,” said Gerardo Antonio Umanzor Funez, lead investigator and medical oncologist at Centro Oncologico Integral, working with DEMEDICA of San Pedro Sula, Honduras. “The lessened burden of neuropathy, the ability to manage GI side effects with prophylactic treatments, and the convenience of home-based administration, could be transformational in the treatment of metastatic breast cancer, especially in the current environment.”
Blueprint Medicines’ Pralsetinib for Thyroid Cancer
Blueprint Medicines had a target action date of February 28 for its NDA for pralsetinib for patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer. It was accepted for review under the agency’s Real-Time Oncology Review (RTOR) pilot program. It’s designed to assess a more efficient review process. It was approved on December 1, 2020, and will be marketed as Gavreto (pralsetinib).
The approval expanded the labeled indications for Gavreto to include adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory, if radioactive iodine was appropriate.
Gavreto is a once-daily oral therapy that potently and selectively targets RET alterations that drive multiple tumor types. It is jointly commercialized in the U.S. by Blueprint and Genentech, a Roche company.
CorMedix’ Defencath for Bloodstream Infections Associated with Catheters in Hemodialysis Patients
CorMedix has a target action date of February 28 for its NDA for Defencath for the treatment of life-threatening bloodstream infections associated with the use of central venous catheters in patients receiving chronic hemodialysis. It has been designated by the FDA as a Fast Track and Qualified Infectious Disease Product, which offers an additional five years of marketing exclusivity.
On November 18, 2020, the company announced that the FDA had decided to cancel the Antimicrobial Drug Advisory Committee meeting that had been tentatively scheduled for January 14, 2021, to discuss the NDA.
Defencath is a proprietary formulation of taurolidine 1.35%, citrate 3.5% and heparin 1000 units/mL. Taurolidine is an amino acid derivative that has broad antimicrobial activity against gram-positive and -negative bacteria, including antibiotic resistant strains, in addition to mycobacteria and clinically relevant fungi including Aspergillus. The company also is working to develop Defencath as a catheter lock solution for use in oncology and total parenteral nutrition patients.
Sanofi’s Libtayo for Advanced Non-Small Cell Lung Cancer
Sanofi had a target action date of February 28 under Priority Review of Libtayo (cemiplimab-rwlc) for advanced non-small cell lung cancer with 50% PD-L1 expression. Libtayo is a fully human monoclonal antibody that targets the PD-1 immune checkpoint receptor on T-cells. On February 22, 2021, the FDA approved Libtayo for this indication. The patients must either have metastatic or locally advanced tumors that are not candidates for surgery or definitive chemoradiation, and the tumors must not have EGFR, ALK or ROS1 aberrations. The PD-L1 expression level is determined by an FDA-approved test.
“The approval of Libtayo to treat first-line advanced non-small cell lung cancer with high PD-L1 expression means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, Price Family Professor of Medicine, Director of Thoracic Oncology and Co-director of Cancer Immunotherapy at Columbia University Irving Medical Center. “Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases, or who had locally advanced disease and were not candidates for definitive chemoradiation.”
KemPharm’s KP415 for ADHD
KemPharm has a target action date of March 2 for the NDA for KP415 for treatment of attention deficit hyperactivity disorder (ADHD). The drug is made up of serdexmethylphenidate (SDX), the company’s prodrug of d-methylphenidate (d-MPH), co-formulated with immediate-release d-MPH. It is designed to address unmet needs with the most widely-prescribed methylphenidate ADHD treatments, including earlier onset of action, longer duration of therapy, and avoiding unnecessary spikes in d-MPH concentrations.
On December 2, 2020, after a Late-Cycle Communication Meeting with the FDA, company president and chief executive officer Travis Mickle stated, “The late-cycle review meeting with the FDA continued a series of productive meetings with the agency, and sets the stage for the next phase of the NDA review process, including the potential for confidential discussions of the KP415 product label.”
Gilead and Kite’s Yescarta for R/R Follicular Lymphoma and Marginal Zone Lymphoma
Gilead Sciences and Kite Pharma, a Gilead company, have a target action date of March 5 for their Yescarta (axicabtagene ciloleucel) for the treatment of follicular lymphoma (FL) and marginal zone lymphoma (MZL). The results from the ZUMA-5 clinical trial was the basis for the supplemental Biologics License Application (sBLA).
On December 5, 2020, the companies announced results from the primary analysis of ZUMA-5, a Phase II trial of Yescarta in adults with r/r indolent non-Hodgkin lymphoma (iNHL) after at least two previous lines of therapy. In the trial 92% of iNHL patients responded, including 76% with a complete response (CR) at a median follow-up of 17.5 months. The drug had previously been granted a Breakthrough Therapy Designation (BTD) by the FDA for FL and MZL.
“It is encouraging to see this level of response to CAR T-cell therapy in a heavily pretreated and multiply relapsed patient population, in whom response duration to other available therapies is expected to be short,” said Caron A. Jacobson, medical director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute and Assistant Professor of Medicine, Harvard Medical School.