Regulatory Focus™ > News Articles > 2020 > 8 > FDA Approvals Roundup: Monjuvi, Spravato, Epidiolex

FDA Approvals Roundup: Monjuvi, Spravato, Epidiolex

Posted 05 August 2020 | By Renee Matthews 

FDA Approvals Roundup: Monjuvi, Spravato, Epidiolex

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).

New approvals
Monjuvi okayed as novel therapy for diffuse large B-cell lymphoma
MorphoSys’ Monjuvi (tafasitamab-cxix IV infusion) has been approved for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The novel CD19-directed cytolytic antibody is indicated in combination with lenalidomide for patients with DLBCL, including DLBCL arising from low-grade lymphoma, and patients who are not eligible for autologous stem-cell transplant.
The approval was based on efficacy findings for Monjuvi with lenalidomide in L-MIND, an open-label, multicenter, single-arm study. Overall response rate (ORR) in 71 patients diagnosed with DLBCL was 55% (95% confidence interval, 43%-67%), with complete responses in 37% of patients and partial responses in 18%. Median response duration was 21.7 months.
The indication received an accelerated approval based on the ORR data. Continued approval might depend on demonstration of clinical benefit in confirmatory trials. The application had received priority review, fast track, breakthrough, and orphan product designations. The agency’s review was facilitated by use of the assessment aid.
MorphoSys and Xencor signed an exclusive worldwide license and collaboration agreement in 2010 for development and commercialization of Monjuvi, then known as XmAb5574. Under that agreement, Xencor will receive a $25-million milestone payment from MorphoSys following the drug’s approval. MorphoSys and Incyte will comarket the drug in the US.
The European Medicines Agency is currently reviewing a marketing authorization application for the therapy.
Monjuvi incorporates Xencor's XmAb antibody engineering platform, which enhances the antibody’s performance.
New indications
Spravato approved for adults with major depressive disorder with suicidal ideation
Janssen’ Spravato (esketamine nasal spray) has received approval for use in combination with an oral antidepressant in treating depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.
It is the first approved therapy shown to reduce depressive symptoms within 24 hours of administration. However, its effectiveness in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated.
The supplemental new drug application for Spravato was approved based on findings from two randomized, placebo-controlled, double-blind phase 3 clinical trials, ASPIRE 1 and 2 in which 226 and 230 patients, respectively, received Spravato with standard-of-care treatment or placebo. Researchers used the Montgomery-Åsberg Depression Rating Scale (MADRS) to assess symptom severity.
At 24 hours after the initial dose of the study drug, patients in the two studies had 15.9- and 16.0-point decreases on the MADRS, compared with 12.0- and 12.2-point decreases in the placebo group receiving standard care alone. Both groups continued to improve between 4 hours and 25 days, with 41% and 43% of Spravato patients achieving clinical remission of depression, compared with 34% and 27% in placebo patients.
There was no statistically significant difference between the two groups on the secondary endpoint of improvement in severity of suicidality at 24 hours, with both groups showing a similar reduction on the measure. The safety profile for Spravato was consistent with previous studies in treatment-resistant depression.
The drug was approved in 2019 as a therapy for treatment-resistant depression (TRD). That approval has a boxed warning for a risk evaluation and mitigation strategy (REMS) and risk of suicidal thoughts and behaviors. It will be made available at REMS certified treatment centers.
The esketamine nasal spray was granted breakthrough therapy designation. It has been submitted for review for TRD, and for adults with MDD with suicidal ideation with intent, in Europe and other countries.
Epidiolex gets new indication for seizures in tuberous sclerosis complex
Greenwich Biosciences’ Epidiolex (cannabidiol [CBD] oral solution) has received an expanded indication for treatment of seizures associated with tuberous sclerosis complex (TSC) in patients aged 1 year or older. TSC is a rare genetic disease that causes benign tumors to grow in the brain and other parts of the body, causing seizures, developmental delay, and behavioral problems
The drug was originally approved in 2018 for treating seizures associated with Lennox-Gastaut and Dravet syndromes, both rare and severe forms of epilepsy. It is the second drug approved for TSC-related seizures after everolimus, also in 2018.
Epidiolex’s effectiveness in the expanded indications population was demonstrated in a randomized, double-blind, placebo-controlled trial in which 148 patients of 224 received the study drug. Patients receiving Epidiolex had a significantly greater reduction in the frequency of seizures during the 16-week treatment period than those receiving placebo. The effect was seen within 8 weeks of treatment initiation.
Epidiolex must be dispensed with a patient medication guide that describes important information about the drug’s uses and risks.
The drug received a priority review designation for this application.
Tecentriq picks up expanded indication for mutated metastatic melanoma
Genentech’s Tecentriq (atezolizumab) has been approved in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.
The approval was based on evaluation of the drug combination’s efficacy in a double-blind, randomized, placebo-controlled trial with 514 patients. Findings showed that median progression-free survival was 15.1 months (95% confidence interval, 11.4-18.4) in the Tecentriq  combination arm, and 10.6 months (95% CI, 9.3-12.7) in the placebo arm (hazard ratio, 0.78; 95% CI, 0.63-0.97; P = .0249).
This application was granted priority review and Tecentriq was granted orphan product designation. This review used the assessment aid. FDA collaborated with Swissmedic on the review of this application as part of Project Orbis.
Stelara use now includes plaque psoriasis in children
Janssen’s Stelara (ustekinumab injection) has received an expanded indication for treating the skin lesions or plaques associated with moderate to severe plaque psoriasis in children aged 6-11 years.
The therapy targets the cytokines, interleukin-12 and -23 (IL-12, IL-23), which regulate the inflammatory responses in autoimmune conditions, such as plaque psoriasis. It is the first biologic treatment in this patient population to target the IL-12 and -23 pathways.
This approval of Stelara was based on findings from CADMUS Junior, an open-label, single-arm, multicenter, phase 3 study of 44 patients with moderate to severe plaque psoriasis. At week 12, after receiving two doses, 77% of patients achieved clear or almost clear skin. Results also showed that, at week 12, 84% and 64% of patients achieved improvements of 75% and 90%, respectively, in their Psoriasis Area and Severity Index, compared with baseline. Stelara’s safety profile in CADMUS Junior was similar to those in adult studies.
Stelara has received previous approvals for treating adults and pediatric patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. It has also been approved for use in adults aged 18 years or older with active psoriatic arthritis (with or without methotrexate); moderately to severely active Crohn's disease; or moderately to severely active ulcerative colitis.


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