Princeton, N.J.-based Urogen Pharma Ltd. is transforming itself into a commercial operation in anticipation of an FDA approval for UGN-101 this week. Wall Street also apparently expects a positive decision by the April 18 PDUFA date, as listed in BioWorld’s Drugs on Deck record. Urogen’s stock (NASDAQ:URGN) has climbed 40% since the month began, and 11.31%, or $2.41, on April 13, closing out the day at $23.71.

The mitomycin gel would be the company’s first approved product and the first non-surgical therapy for low-grade upper tract urothelial cancer (UTUC). Granted priority review last December, it also has orphan drug, fast track and breakthrough therapy designations for the indication.

The NDA, initiated in December 2018, is based on data from the pivotal phase III Olympus trial in which UGN-101 demonstrated a complete response rate of 59% and a durability of response of about 89% at six months and 84% at 12 months, according to a Kaplan Meier analysis. The median time to recurrence was estimated to be 13 months, and adverse events were most commonly mild to moderate ureteric stenosis, urinary tract infection, hematuria, flank pain, nausea, dysuria, renal impairment and vomiting. About 8.5% of patients had severe ureteric stenosis. The pivotal trial began in the first quarter of 2017 and treated 71 patients.

With no drugs approved for low-grade UTUC, the current standard of care is radical nephroureterectomy, which is a complete kidney and upper urinary tract removal. Another option, in some cases, is an endoscopic tumor resection followed by mitomycin treatment. Basic anatomy and physiology, however, makes it a difficult option and there are high rates of recurrence, requiring multiple procedures.

Aside from UGN-101, Urogen also is developing another lead candidate, UGN-102 (mitomycin gel), for low-grade non-muscle invasive bladder cancer (NMIBC). Both candidates come from the company’s RTGel reverse-thermal hydrogel platform, which aims to improve therapeutic profiles of existing drugs and enables longer exposure of the urinary tract tissue to medications, potentially ablating tumors without surgery. UGN-101 is targeting a U.S. population of about 6,000 to 7,000 patients with UTUC, while UGN-102 is targeting about 80,000 patients in the U.S. It also has orphan drug designation. Urogen has recently completed enrollment in an open-label, single-arm phase IIb trial of UGN-102.

Urogen’s drug formulations are instilled intravesically in liquid form directly into the bladder or upper urinary tract via catheters. The liquid converts into a gel at body temperature and gradually dissolves upon contact with urine and releases the active drug over several hours. Mitomycin is typically administered using a water-based solution, which has a short dwell time limited to the first voiding of the bladder. Several in vitro models and studies, as well as computer simulations, suggest an increased dwell time of mitomycin in the bladder results in a longer time before cancer recurrence.

In preparation for an approval of UGN-101, Urogen announced on March 23 four promotions of its executive leadership team and one departure as it transforms into a commercial company. If approved, a launch is expected by mid-year 2020. The promotions include making Jeff Bova chief commercial officer and James Ottinger executive vice president of regulatory affairs and quality. Marina Konorty is becoming executive vice president of research and development and technical operations, while Elyse Seltzer will be chief development officer. The company’s chief operating officer, Stephen Mullenix, was expected to leave the company with his duties transferring to Bova, Konorty and Ottinger.

Other companies in line for FDA approvals this month include Paris-based Sanofi SA, San Diego-based Neurocrine Biosciences Inc. and Silver Spring, Md.-based United Therapeutics Corp.

Sanofi’s Menquadfi is a vaccine candidate to help prevent meningococcal meningitis in people ages 2 and older. The FDA accepted the BLA for review in June 2019, and the PDUFA date is set for April 25.

Neurocrine’s opicapone is a catechol-O-methyltransferase inhibitor targeting Parkinson’s disease with a PDUFA scheduled for April 26. The company announced, however, on April 3, that it will delay the commercial launch of opicapone until later this year due to the COVID-19 pandemic and the ability of its Porto, Portugal-based partner, Bial Group, to adequately supply commercial inventory.

United Therapeutics’ Trevyent (treprostinil) is on deck to treat pulmonary arterial hypertension with an April 27 PDUFA date. The company anticipates a delay or a complete response letter, however, due to information requests from the FDA citing several deficiencies in the NDA, which was submitted in June 2019.

Astrazeneca plc, of Cambridge, U.K., is also expecting FDA decisions sometime in the second quarter for its antibody-drug conjugate, DS-8201, to treat HER2-positive metastatic breast cancer, and for its PARP inhibitor, Lynparza (olaparib), to treat metastatic castration-resistant prostate cancer and advanced ovarian cancer. DS-8201 ([Fam-] trastuzumab deruxtecan) is partnered with Daiichi Sankyo Co. Ltd., of Tokyo, and Lynparza is partnered with Merck & Co. Inc., of Kenilworth, N.J.

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