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Regulatory Focus™ > News Articles > 2020 > 10 > FDA Approvals Roundup: Alkindi, Haegarda, Kalydeco

FDA Approvals Roundup: Alkindi, Haegarda, Kalydeco

Posted 07 October 2020 | By Renee Matthews 

FDA Approvals Roundup: Alkindi, Haegarda, Kalydeco

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).
New approvals
Alkindi approved as replacement therapy in children with adrenocortical insufficiency
Eton Pharmaceuticals’ Alkindi Sprinkle (hydrocortisone oral granules) has been approved as a replacement therapy for adrenocortical insufficiency (AI) in children younger than 17 years. It is the first FDA-approved granular, lower-dose hydrocortisone formulation tailored for easier administration to children with AI and offering more flexible dosing options.
The approval was supported by findings from six clinical studies, including the only interventional Phase 3 study of the oral hydrocortisone in neonates and children younger than 8 years with AI. The application for this indication received orphan drug designation.
Until now, oral hydrocortisone was approved in tablet form only, at 5 mg or more. Since children require much lower doses of the therapy, Alkindi Sprinkle will now be available in 0.5-mg, 1-mg, 2-mg, and 5-mg strengths, which will help clinicians adjust dosing based individual patients’ needs and levels of tolerability.
Pediatric AI is a rare disease in which patients cannot synthesize and release cortisol, and sometimes aldosterone, which results in abnormal sexual development in females and premature puberty and growth termination. The condition can have deadly outcomes, such as adrenal crisis.
New indications
Haegarda gets expanded indication for preventing HAE attacks in children
CSL Behring’s Haegarda (C1 esterase inhibitor injection) has received an expanded indication for preventing hereditary angioedema (HAE) attacks in patients aged 6 years or older.
HAE is a rare, genetic condition causing painful episodic edema in the abdomen, larynx, face, and extremities. Haegarda is the first subcutaneous treatment option for preventing HAE events in younger patients. The therapy’s label was also updated to include clinical safety data for use during pregnancy.
 Haegarda’s approval was based on results from the multinational, double-blinded, placebo-controlled COMPACT pivotal trial and open-label extension (OLE) in patients with symptomatic HAE.
The pivotal study of 90 patients, of whom 79 completed the trial, included 6 participants aged 17 years or younger. Phase 3 intention-to-treat findings from the study showed that patients receiving the FDA-approved dose of 60 IU/kg of the study drug had a 90% response rate and reductions in their monthly rate of HAE attacks use of rescue medication.
In the OLE study, 9 of the 126 patients were aged 17 years or younger. Patients were treated with Haegarda for a mean of 1.5 years. All 9 pediatric patients had a reduction in the number of HAE attacks. 
Of 23 patients who received the 60-IU/kg dose for more than 2 years, 19 were attack-free during months 25-30 of treatment. Safety and effectiveness of the study drug was consistent with overall study results.
Kalydeco approved for cystic fibrosis for children as young as 4 months
Vertex Pharmaceuticals’ Kalydeco (ivacaftor tablets) has received a new indication for treating cystic fibrosis in children aged 4 to less than 6 months with at least one mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to the drug, based on clinical findings and/or in vitro assay results.
Kalydeco is already approved in the US and EU for treating the disease in patients aged 6 months or older. Cystic Fibrosis is a rare, progressive genetic disease affecting the lungs, liver, GI tract, among others.
Approval of Kalydeco was based findings from the 24-week, Phase 3, open-label, safety cohort of the ARRIVAL study, consisting of six children with cystic fibrosis, aged 4 months to less than 6 months with 1 of 10 mutations in the CFTR. Findings from the cohort showed a similar safety profile to that seen in older children and adult patients.
“Initiating therapy that treats the underlying cause of cystic fibrosis as early as 4 months of age may have the potential to modify the course of the disease,” said Margaret Rosenfeld, MD, MPH, Seattle Children’s Research Institute and Department of Pediatrics, University of Washington School of Medicine, in a press release.
Opdivo-Yervoy combination approved for unresectable mesothelioma
Bristol-Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) have been approved as a first-line combination therapy for adults with unresectable, malignant pleural mesothelioma, a form of cancer caused by inhalation of asbestos fibers. It is the first approval for the disease in 16 years.
This review was conducted under Project Orbis, a collaborative effort between the FDA and international partners for submission and review of oncology drugs. Agencies in Australia, Brazil, Canada, and Switzerland participated in this application.
This review used the real-time oncology review pilot program and the assessment aid. The applications were granted priority review and orphan product designation.
Efficacy was investigated in the randomized, open-label CHECKMATE-743 trial in previously untreated patients with unresectable malignant pleural mesothelioma. Patients were randomized to receive either nivolumab plus ipilimumab for up to 2 years (n = 303) or 6 cycles of combination chemotherapy (n=302).
Patients receiving the combination therapy showed a statistically significant improvement in overall survival (OS) compared with those receiving chemotherapy (median OS, 18.1 months vs. 14.1 months, respectively). Median progression-free survival was 6.8 months in the combination arm, compared with 7.2 months in the chemotherapy arm. Confirmed overall response rate was 40% and 43%, respectively, and median response duration of 11.0 months and 6.7 months.
Simponi Aria provides new therapy option for polyarticular-course JIA and juvenile PsA
Janssen Pharmaceutical’s Simponi Aria (golimumab) has received an extended approval for treating patients aged 2 years or older who have active polyarticular juvenile idiopathic arthritis (pJIA) or active  psoriatic arthritis (PsA).
The polyarticular form of JIA is the most common form of the condition, which is marked by joint inflammation. PsA in children is a rare subtype of JIA, characterized by joint inflammation and skin lesions. Simponi Aria is a fully human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody that targets a protein that causes inflammation when it is overproduced. It is the first therapy of its kind to be approved for children with the indicated conditions.
The approval of Simponi Aria was based on findings from the Phase 3, multinational, open-label GO-VIVA trial in 127 children aged 2-17 years with JIA with active polyarthritis despite receiving methotrexate treatment for at least 2 months. The trial was conducted as a postmarketing condition under the Pediatric Research Equity Act after the therapy’s initial 2013 approval for adults with moderate to severe active rheumatoid arthritis (RA).
Results in the pediatric study showed pharmacokinetic exposure to Simponi Aria was consistent with findings from the pivotal Phase 3 clinical trials in adults. Efficacy and safety were assessed though 52 weeks of treatment and both were deemed commensurate with findings in the adult study population.

Tags: FDA, US

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