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Regulatory Focus™ > News Articles > 2020 > 8 > FDA Roundup: Kyprolis, Kesimpta, Cystadrops

FDA Roundup: Kyprolis, Kesimpta, Cystadrops

Posted 26 August 2020 | By Renee Matthews 

FDA Roundup: Kyprolis, Kesimpta, Cystadrops

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).
New indications
Kyprolis in triple combo approved for previously treated multiple myeloma
Amgen’s Kyprolis (carfilzomib) has received an expanded indication as a once- or twice-weekly combination with Janssen’s Darzalex (daratumumab) and dexamethasone for relapsed or refractory multiple myeloma in patients previously treated with immunomodulatory drug based (IMiD) therapies.
The incurable blood cancer is marked by recurrent remission and relapse, with worse outcomes with each relapse. Patients typically receive frontline treatment with IMiD therapies through progression, but eventually need an lMiD-free regimen on relapse. The triplet combination, known as DKd, provides an lMiD-free treatment option for relapsed patients.  
Approval for the expanded indication was based on findings of the CANDOR and EQUULEUS trials. The  randomized, open-label phase 3 CANDOR trial in 466 patients with previously treated relapsed or refractory disease compared twice weekly Kyprolis within the DKd combination with Kyprolis and dexamethasone alone. The primary endpoint was progression-free survival. There was a 37% reduction in the risk of disease progression or death in patients treated with DKd (hazard ratio, 0.63; 95% confidence interval, 0.464-0.854; P = .0014), compared with Kyprolis and dexamethasone alone. DKd safety was in line with the safety of the separate components.Safety and efficacy findings from the open-label, multicohort, phase 1b EQUULEUS trial also supported approval of the once-weekly dosing of Kyprolis within the DKd combination.
Kyprolis was originally approved in 2012 as a therapy for previously treated patients who have received previous treatments combined with dexamethasone alone, dexamethasone with lenalidomide, or dexamethasone with daratumumab. It was also approved as a standalone therapy for patients with relapsed or refractory disease who have received one or more lines of therapy.
Ofatumumab repackaged as Kesimpta, an at-home therapy for relapsing multiple sclerosis
Novartis’s Kesimpta (ofatumumab injection) has received a new indication for the treatment of relapsing forms of multiple sclerosis. It is the first B-cell therapy approved for monthly at-home, self-administration using the Sensoready autoinjector pen3.   
Ofatumumab is also marketed as Arzerra, which was approved in 2009 for use in patients with chronic lymphocytic leukemia.
“In the key clinical studies, this breakthrough treatment produced a profound reduction in new brain lesions, reducing relapses and slowing underlying disease progression,” said Stephen L. Hauser, MD, director of the UCSF Weill Institute for Neurosciences and co-chair of the steering committee for the ASCLEPIOS I and II studies.
Approval for the new indication was based on safety and efficacy findings in the multinational, double-blind, randomized phase 3 ASCLEPIOS I and II studies comparing Kesimpta with teriflunomide in 1,882 adults with relapsing multiple sclerosis. The primary endpoint was annualized relapse rate (ARR). Findings showed AAR reductions of 51% and 59% in ASCLEPIOS I and II, respectively, compared with teriflunomide (P < .001 in both studies). The study drug was also associated with a relative risk reduction of 34.4% (P = .002) in 3-month confirmed disability progression, compared with teriflunomide.
In addition, there was a significant reduction in new or enlarging lesions with Kesimpta compared with teriflunomide, and findings from a post hoc analysis suggested Kesimpta may stall new disease activity. The drug’s safety profile is similar to that of teriflunomide.
Kesimpta is expected to be available in the United States in early September. The company has submitted regulatory applications in other countries, with approval for the drug in Europe is expected in the second quarter of 2021.
Cystadrops gets new formulation, dosing regimen for ocular crystal build-up in cystinosis
Recordati’s Cystadrops (cysteamine ophthalmic solution, 0.37%) has been approved with a new formulation and dosing regimen for use in adults and children for reducing build-up of corneal cystine crystals associated with cystinosis, a rare genetic disorder. The viscous ophthalmic eye-drop formulation is applied four times daily, during waking hours.
Cysteamine ophthalmic solution was previously approved in 2012 as Cystaran, a 0.44% topical ophthalmic treatment, used hourly during waking hours, for the same indication. That approval was granted to Sigma-Tau Pharmaceuticals, which developed the therapy in partnership with the National Institutes of Health.
Cystinosis is caused by the accumulation of the amino acid cystine in the body’s cells, forming crystals that coalesce and cause damage to cells and organs throughout the body, especially the eyes and kidneys.
Approval of Cystadrops was based on findings in two clinical trials in which patients with cystinosis and corneal crystal build-up received Cystadrops at a median of four times daily. A phase 3 open-label, randomized, controlled trial with 32 patients (age range, 3-63 years; 15 in the study arm), assessed reduction in corneal cystine crystal density using in vivo confocal microscopy (IVCM). After 90 days, patients using Cystadrops had a 40% reduction from baseline on the IVCM total score across all corneal layers.
A phase 1/2a open-label, adaptive dose-response, single-arm study of 8 patients (age range, 7-21 years) with cystinosis demonstrated a reduction of 30% in the IVCM crystal density measure in patients treated with Cystadrops. That reduction was maintained throughout the study period of 5 years.

Tags: FDA, US

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