FDA Approvals Roundup: Zepzelca, Ilaris, Lyumjev

RoundupsRoundups | 17 June 2020 |  By 

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).
New approvals
Zepzelca handed accelerated approval for metastatic SCLC in adults
Jazz Pharmaceuticals and PharmaMar’s Zepzelca (lurbinectedin) has been granted accelerated approval for adult patients with metastatic small cell lung cancer (SCLC) whose disease has progressed during or after platinum-based chemotherapy.
The indication was approved based on overall response rate (ORR) and duration of response. Its continued approval may depend on verification and description of clinical benefit in confirmatory trials.
FDA granted Zepzelca orphan drug designation for the treatment of SCLC and priority review to this application. The review was conducted under Project Orbis, a collaborative, international review process for oncology products between FDA and other regulators. FDA collaborated with Australia’s Therapeutic Goods Administration (TGA) on this application. The US agency approved this application 2 months ahead of the goal date, and the review is ongoing for the TGA.
Zepzelca is a highly selective inhibitor of trans-activated RNA polymerase II transcription. Its efficacy, denoted by ORR and response duration, was demonstrated in the open-label, multicenter, multicohort PM1183-B-005-14 trial with 105 patients matching the indicated population. Among those 105 patients, ORR was 35% (95% confidence interval, 26%-45%) and the median response duration, 5.3 months (95% CI, 4.1-6.4). An independent review committee put ORR at 30% (95% CI, 22%-40%) and the median response duration at 5.1 months (95% CI, 4.9-6.4).
Semglee okayed for diabetes
Mylan and Biocon Biologic’s Semglee (insulin glargine injection) has been approved by FDA for glycemic control in adults and children with type 1 diabetes and in adults with type 2 diabetes.
Semglee is a long-acting human insulin analogue. It has an identical amino acid sequence to Sanofi’s insulin glargine injection, Lantus, and is approved for the same indications.
The application was approved under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act and was deemed to be a biologic under section 351(a) of the Public Health Service Act. That means that Semglee can be a reference for a proposed insulin glargine biosimilar or interchangeable biosimilar product, Patrick Archdeacon, MD, acting associate director for therapeutics in the Division of Diabetes, Lipid Disorders and Obesity, Office of New Drugs, noted in a statement.
Once available, FDA-approved biosimilar and interchangeable insulin products are expected to expand competition and ultimately empower patients by increasing choices and potentially lowering prices of safe, effective, high-quality medications, Archdeacon added.
The therapy was approved on the basis of findings from an analytical preclinical and clinical program, including the randomized INSTRIDE studies, in patients with type 1 and type 2 diabetes. The findings confirmed Semglee’s pharmacokinetic and pharmacodynamic properties, efficacy, safety and immunogenicity compared with Lantus.
INSTRIDE 1 was a 52-week noninferiority study in 558 patients with type 1 diabetes, and INSTRIDE 2 was a 24-week study in 560 patients with type 2 disease. The primary endpoint was change from baseline in hemoglobin A1c levels over 24 weeks. Semglee was found to be noninferior to Lantus on that measure. The safety, efficacy and immunogenicity data also indicated no differences between the study and control arms.
Lyumjev approved as rapid-acting insulin for adults with type 1 or type 2 diabetes
Eli Lilly’s human insulin analog Lyumjev (insulin lispro-aabc injection) has been approved by FDA for improving glycemic control in adults with type 1 or type 2 diabetes.
The rapid-acting, mealtime insulin is a novel formulation of insulin lispro, developed to speed the absorption of insulin into the blood stream and reduce hemoglobin A1c levels. It controls high blood sugar levels after meals in adults with diabetes, mirroring the way natural insulin works after meals in healthy individuals.
Lyumjev has been approved by regulatory authorities in several global markets, including Japan and the European Union in March 2020.
The approval was based on data from the randomized, controlled, treat-to-target phase 3 PRONTO-T1D and PRONTO-T2D studies, comparing Lyumjev and Lilly’s Humalog (insulin lispro injection) in the indicated population. Both studies met the primary endpoint of noninferior hemoglobin A1c reduction from baseline, compared with Humalog at 26 weeks, when dosed at mealtime. Key endpoints were adjusted for multiple testing, including the comparisons of 1- and 2-hour postprandial glucose. In both studies, Lyumjev achieved superior reduction in blood glucose spikes at both time points compared with Humalog.
Uplizna approved as new therapy option for rare autoimmune disease
FDA has approved Viela Bio’s Uplizna (inebilizumab-cdon injection) for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease of the central nervous system. The disease affects mainly the optic nerves and spinal cord in adult patients who are positive for the anti-aquaporin-4, or AQP4, antibody.
The biologic is only the second approved treatment for the disorder. It had previously received orphan drug and breakthrough therapy designations from the agency.
In 2019, the agency approved Soliris (eculizumab injection) for the same indication and patient population as Uplizna. A biologics license application for anti-IL6R satralizumab as a possible treatment for NMOSD is currently under review at FDA.
Uplinza’s effectiveness for the treatment of NMOSD was demonstrated in a clinical study of 230 adult patients. In all, 213 of the 230 patients had antibodies against AQP4. During the 197-day study, there was a 77% reduction in the risk of an NMOSD relapse in the 161 who were anti-AQP4 antibody positive and received the study drug compared with placebo-treatment group. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.
Nyvepria approved for offsetting infection in patients on anticancer drugs
Pfizer’s Nyvepria (pegfilgrastim-apgf), a biosimilar to Amgen’s Neulasta (pegfilgrastim), has been approved by FDA to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies being treated with anticancer drugs associated with febrile neutropenia.
FDA approval of the long-acting supportive care therapy was based on the review of a comprehensive data package and evidence demonstrating a high degree of similarity between Nyvepria and its Neulasta reference product.
New/extended indications
Ilaris debuts as first treatment for adult-onset Still's disease
FDA has approved Novartis’s Ilaris (canakinumab) injection for the treatment of active and adult-onset Still's disease (AOSD), making it the first approved therapy for this rare and serious autoinflammatory disorder.
There is considerable overlap in the characteristics of AOSD and systemic juvenile idiopathic arthritis, for which Ilaris was approved in 2013 for patients aged 2 years or older. Ilaris blocks the effects of the cytokine interleukin-1, which has a role in regulating the immune system and suppressing inflammation.
Ilaris was granted priority review designation.
Tivicay given the green light for infants, children with HIV
Viiv Healthcare’s Tivicay and Tivicay PD (dolutegravir) have been approved by FDA to treat HIV-1 infection in pediatric patients at least 4 weeks old and weighing 6.61 pounds (3 kg) or more, in combination with other antiretroviral treatments.
The integrase inhibitor is intended for previously untreated young patients with HIV or those who have been treated, but not with an integrase inhibitor. The drug is available in tablet form (Tivicay) and is the first integrase inhibitor also available as a dispersible tablet for oral suspension (Tivicay PD), making it easier for younger children to take, the company said in a statement.
The drug was originally approved in 2013 for HIV-infected adults and children aged 12 years or older. The most recent application received priority review designation. Tivicay PD and the extended indication of the Tivicay tablet are currently under review by the European Medicines Agency (EMA).
Mylotarg indication extended for children with CD33-positive AML
FDA has extended the indication of Wyeth’s Mylotarg (gemtuzumab ozogamicin) to the treatment of newly diagnosed, CD33-positive acute myeloid leukemia (AML) in pediatric patients aged 1 month or older.
Mylotarg is a recombinant, humanized anti-CD33 antibody-drug conjugate. The agency had previously granted it orphan drug status and had designated it for priority preview.
In 2017, the agency approved the drug, then manufactured by Wyeth Pharmaceuticals for Pfizer, as a therapy for adults with newly diagnosed, CD33-positive AML and for treating relapsed or refractory CD33-positive AML in adults and in pediatric patients aged 2 years or older. The therapy carries a black box warning for hepatotoxicity.
Opdivo gets new indication for advanced esophageal SCC
FDA has approved Bristol-Myers Squibb’s Opdivo (nivolumab) for patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (SCC), who have received prior fluoropyrimidine- and platinum-based chemotherapy.
This review used the assessment aid, a voluntary submission from the applicant to facilitate the agency’s assessment. The supplemental biologics license application was granted priority review and the drug received orphan drug designation.
The immunotherapy was originally approved in 2014 for advanced melanoma and has since received numerous expanded indications for lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, colorectal cancer and hepatocellular carcinoma.
Keytruda now also indicated for TMB-H solid tumors
Merck’s Keytruda (pembrolizumab) has been approved as a monotherapy for unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors, as determined by an FDA-approved test, in adult and pediatric patients whose disease has progressed despite treatment or who have no alternative treatment options.
The agency also approved a diagnostic companion to the drug, the FoundationOne CDx test, to identify patients with solid tumors that are TMB-H (≥10 mutations/megabase) who may benefit from immunotherapy treatment with Keytruda monotherapy.
The indication for the checkpoint inhibitor was approved under accelerated approval pathway, based on tumor response rate and durability of response. Continued approval for this indication may depend on verification and description of clinical benefit in the confirmatory trials. Keytruda’s safety and effectiveness in pediatric patients with TMB-H central nervous system cancers have not been established.
Keytruda was first approved in 2014 as a therapy for advanced melanoma. Subsequent expanded indications have been for non‒small cell lung cancer, Hodgkin lymphoma and cervical cancer, among others.
Cosentyx gets new indication to treat active non-radiographic axial spondyloarthritis
FDA has approved Novartis’s Cosentyx (secukinumab) for the treatment of active nonradiographic axial spondyloarthritis (nr-axSpA), which is part of the axial spondyloarthritis disease spectrum.
This is the fourth indication for Cosentyx. It is the first and only fullyhuman monoclonal antibody that directly inhibits interleukin-17A (IL-17A), an important cytokine involved in the inflammation and development of psoriatic arthritis, plaque psoriasis, ankylosing spondylitis and nr-axSpA. The drug was originally approved in 2015 for the treatment of moderate to severe plaque psoriasis in adult patients.
In April 2020, EMA also approved Cosentyx for the treatment of nr-axSpA15.


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