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Monday, August 12, 2019

FDA Action Alert: Regeneron, Kala and Vanda

Now that July has come and gone, the U.S. Food and Drug Administration (FDA) is back to work approving drugs. This week marks three PDUFA target action dates, although one has already been rejected and another hit a snag that doesn’t appear to affect the decision date. Here’s a look.
Regeneron Pharmaceuticals’ Eylea for Pre-filled Syringe
Regeneron Pharmaceuticals has a target action date of August 12 for its supplemental Biologics License Application (sBLA) for its Eylea (aflibercept) in a pre-filled syringe. The drug was approved in May for diabetic retinopathy. Overall, the drug is approved for diabetic retinopathy, diabetic macular edema (DME), wet age-related macular degeneration (AMD) and macular edema following retinal vein occlusion (MEfRVO). Net sales for the second quarter of 2019 of the drug were $1.16 billion, an increase of 17% compared to the second quarter of 2018.
Kala Pharmaceuticals’ Dry Eye Disease Medication
Kala Pharmaceuticals, based in Waltham, Massachusetts, had a target action date of August 15 for its New Drug Application (NDA) for KPI-121 0.25% for temporary relief of dry eye disease using a two-week course of therapy. However, the FDA issued a complete response letter (CRL) on August 8, indicating that the company would need to conduct another clinical trial focused on efficacy data for a resubmission.

The company is still enrolling patients in its ongoing STRIDE 3 Phase III clinical trial, which it believes will be the basis of its response to the CRL. It is expecting topline data from STRIDE 3 by the end of this year and plans the NDA resubmission during the first half of 2020, which would be reviewed within six months.
“We remain confident in the potential of KPI-121 0.25% to be the first approved product for the temporary relief of the signs and symptoms of dry eye disease,” stated Kim Brazzell, Kala’s chief medical officer. “We look forward to reporting data from STRIDE 3 and resubmitting the NDA with the goal of obtaining approval and being able to offer KPI-121 0.25% to the millions of patients with dry eye disease.”
The drug uses the company’s AMPPLIFY mucus-penetrating particle (MPP) Drug Delivery Technology. If approved, it will be the first product for the temporary relief of signs and symptoms of dry eye disease, including treatment of dry eye flares.
“All currently marketed FDA-approved pharmaceutical treatments for dry eye disease are chronic therapies and are typically used in patients with chronic or persistent dry eye symptoms,” stated Edward Holland, director of Cornea Services, Cincinnati Eye Institutes and professor of Clinical Ophthalmology, University of Cincinnati. “The vast majority of patients experience episodic dry eye flares that are characterized by acute exacerbations of signs and/or symptoms. An FDA-approved, safe and effective short-term treatment for dry eye disease, including dry eye flares, will represent an important new treatment option for patients and prescribers.”
Vanda Pharmaceuticals Hetlioz for Jet Lag
Vanda Pharmaceuticals has a target action date of August 16 for its supplemental New Drug Application (sNDA) for Hetlioz (tasimelteon) for the treatment of jet lag disorder. The drug is currently approved to treat Non-24 Hour Sleep Wake Disorder. The drug is a melatonin receptor agonist and is approved for the use in the U.S. and Europe.

On July 22, Vanda indicated it received a notification from the FDA saying that as part of the agency’s ongoing review of the Netlioz sNDA, it had “identified deficiencies that preclude discussion of labeling and postmarketing requirements/commitments at this time. No deficiencies were disclosed by the FDA in this notification, and the FDA stated that this notification does not reflect a final decision on the information under review.”
It is not clear if this will delay the PDUFA date of August 16, although it doesn’t seem to have. In the company’s second-quarter report, Vanda indicated it plans to “await the PDUFA action and work expeditiously to resolve any potential deficiencies.”
Vanda also indicated it expects to file a sNDA for Hetlioz for the treatment of Smith-Magenis Syndrome in this year’s third quarter, and initiate a Phase II trial of the drug in delayed sleep phase disorder (DSPD) in patients who have a mutation in the CRY1 gene, which is believed to be causative in a subpopulation of DSPD patients.
In the second quarter, Vanda reported Hetlioz net product sales of $37.8 million, a 31% increase compared to the $29 million in the first quarter of the year.

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