FDA Approvals Roundup: Imcivree, Danyelza, Ga 68 PSMA-11

RoundupsRoundupsRegulatory NewsRegulatory News | 02 December 2020 | By

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).
New approvals
Imcivree okayed as first therapy for managing obesity in some rare genetic conditions
Rhythm Pharmaceutical’s Imcivree (setmelanotide) has been approved for chronic weight management in patients aged 6 years or older with obesity related to three rare genetic conditions.
Imcivree is the first treatment approved for pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin type 1 (PCSK1) deficiency, and leptin receptor (LEPR) deficiency. The conditions are confirmed by genetic testing showing variants in pathogenic POMC, PCSK1, or LEPR genes. The drug is not approved for obesity related to benign forms of POMC, PCSK1, or LEPR deficiency or other types of obesity, such as those related to genetic syndromes or general obesity.
Imcivree’s effectiveness was evaluated in two, year-long studies in 21 patients aged 6 years or older. The first study enrolled 10 patients with obesity and confirmed or suspected POMC or PCSK1 deficiency, and the second, 11 patients with obesity and confirmed or suspected LEPR deficiency. Effectiveness was determined by the number of patients who lost more than 10% of body weight after a year of treatment with the study drug. In all, 80% of patients in the first study lost 10% or more of their body weight after that time, and 46% in the second study lost 10% or more.
The FDA granted orphan disease designation, breakthrough therapy designation, and priority review for the application.
Danyelza approved as combination therapy for neuroblastoma
Y-mAbs’ Danyelza (naxitamab-gqgk injection) has been approved as a combination therapy with granulocyte-macrophage colony-stimulating factor for relapsed/refractory, high-risk neuroblastoma in the bone or bone marrow in previously treated adults and children aged 1 year or older showing partial or minor response or with stable disease.
Neuroblastoma is a solid tumor that occurs in the nervous system, outside of the brain. The clinical trajectory can vary significantly; some tumors are treatable, but most are highly aggressive. As a humanized, monoclonal antibody, Danyelza is designed to target the ganglioside GD2, which is highly expressed in sarcomas and tumors of neuroectodermal origin.
This therapy was approved under accelerated approval regulation based on overall response rate (ORR) and duration of response (DoR) from two studies in the indicated population. Continued approval for this indication requires further verification and description of clinical benefits in a confirmatory, postmarketing clinical trial. The ongoing study, known as Study 201, will include a minimum of 80 patients and have ORR and DoR as primary endpoints and progression-free disease and overall survival as secondary endpoints.
The application received priority review, orphan drug, breakthrough therapy, and rare pediatric disease designations from the FDA.
Danyelza was developed by researchers at Memorial Sloan Kettering Cancer Center in New York. The center has licensed the drug exclusively to Y-mAbs.
First PSMA-targeted PET imaging drug approved for prostate cancer
Gallium (Ga) 68 PSMA-11 has been approved as the first drug for positron emission tomography (PET) imaging of lesions positive for prostate-specific membrane antigen (PSMA) in men with prostate cancer. The approval was granted to University of California, Los Angeles, and University of California, San Francisco.
The radioactive diagnostic agent is indicated for patients with suspected prostate cancer metastasis that may be curable with surgery or radiation therapy or with suspected disease recurrence based on elevated levels of serum prostate-specific antigen.
New indications
Xolair nabs expanded indication for nasal polyps in adults
Genentech’s Xolair (omalizumab injection) has received a new indication as an add-on maintenance treatment for nasal polyps in adults aged 18 years or older who do not respond to nasal corticosteroids.
Nasal polyps often occur with respiratory conditions, such as allergies and asthma, which are associated with inflammation. Xolair blocks immunoglobulin E, one of the main drivers of inflammation. The expanded indication makes Xolair the first biologic approved for nasal polyps.
Approval of the supplemental biologics license application was based on efficacy and safety findings from the pivotal, phase 3 POLYP 1 and POLYP 2 studies. The randomized, multicenter, and placebo-controlled studies included 138 and 127 patients, respectively, from the indicated population.

At 24 weeks, patients receiving Xolair showed greater improvement from baseline in Nasal Polyp Score, a measure of the extent and severity of polyps, and the Nasal Congestion Score, compared with controls. Some patients showed improvements as early as 4 weeks out from baseline.
Xolair was originally approved in 2003. It has previous approvals for treating moderate to severe persistent allergic asthma in patients aged 6 years or older whose symptoms are not controlled by current medication, and for chronic idiopathic urticaria in patients aged 12 years or older who do not respond to treatment with H1 antihistamines.
Hetlioz handed new indication for sleep disturbances in Smith-Magenis syndrome
Vanda Pharmaceuticals’ Hetlioz (tasimelteon) has been approved for the treatment of adults and children with nighttime sleep disturbances associated with Smith-Magenis syndrome (SMS), making it the first therapy approved for the rare neurodevelopmental disorder.
Patients with SMS have an inverted circadian rhythm and experience difficulty sleeping during the night. Hetlioz, a melatonin receptor agonist, helps regulate the sleep-wake cycle. It is available as capsules for adults and a liquid formulation for children.
Approval of Hetlioz was based on efficacy findings in a placebo-controlled study of adults and children with SMS. The therapy’s safety profile was similar to profiles in previous studies with Hetlioz for treatment of non‒24-hour sleep-wake disorder and was similar between adults and children with SMS.
Hetlioz was originally approved in 2014 for treating non‒24-hour sleep-wake disorder.
Gavreto gets expanded indications for RET-altered thyroid cancers
Blueprint Medicines’ Gavreto (pralsetinib capsules) has received two new indications for treating advanced or metastatic RET-mutant medullary thyroid cancer (MTC) or RET fusion-positive thyroid cancer in adults and children aged 12 years or older who require systemic therapy but are radioactive iodine-refractory.
The approval was based on efficacy findings in the multicenter, open-label, multicohort ARROW  trial in patients with tumors with RET gene alterations. The main efficacy outcomes were overall response rate (ORR) and duration of response (DoR).
Efficacy was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who received previous treatment with cabozantinib or vandetanib. In those patients, ORR was 60% (95% confidence interval, 46%-73%), and 79% of responders had a DoR of 6 months or longer. ORR in 29 patients with RET-mutant MTC who had not received previous cabozantinib or vandetanib was 66% (95% CI, 46%-82%), with 84% of responders having a DoR of 6 months or longer. In 9 patients with RET fusion-positive thyroid cancer who were radioactive iodine-refractory, ORR was 89% (95% CI, 52%-100%), and all responders had a DoR of 6 months or longer.
This review for the application used the Real-Time Oncology Review pilot program and assessment aid. The application was approved 3 months earlier than the FDA’s goal date.
The application was granted accelerated approval based on the ORR and DoR data. Continued approval for this indication will depend on follow-up verification and description of clinical benefit. The application was also granted priority review, breakthrough therapy, and orphan drug designations.
Gavreto was originally approved in September 2020 for treating adults with RET fusion-positive non-small cell lung cancer.


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