FDA Action Alert: PFEnex, Flexion, Alexion and Clearside


There are several scheduled PDFUA dates for the U.S. Food and Drug Administration (FDA) over the next two weeks. Here’s a look.

PFEnex and its Therapeutic Equivalent for Lilly’s Forteo

Pfenex has a target action date off October 7 for its lead product candidate, PF708 (teriparatide), a therapeutic equivalent for Eli Lilly and Company’s Forteo to treat osteoporosis. PF708 is being evaluated under the FDA’s 505(b)(2) regulatory pathway, which according to Pharmacy Times, “provides manufacturers who have certain types of drugs with an opportunity to acquire FDA approval without performing all the work that’s required with an NDA. These drugs are not strictly generics but are often not entirely novel new molecular entities either. 505(b)(2) can be an option for drugs with a new aspect related to indication, dosage form or regimen, strength, combination with other products, or other unique traits.”

In February 2019, PFEnex and Alvogen expanded a collaboration deal to develop and commercialize PF708 in Europe and in certain countries in Middle East and North Africa (MENA) and Row territories, which is defined as all countries outside of the EU, U.S. and MENA, excluding Mainland China, Hong Kong, Singapore, Malaysia and Thailand. The drug will be commercialized in Europe and Switzerland by Theramex, in MENA by SAJA, a Tamer Group company, and in ROW by Alvogen’s commercialization partners.

The PF708 NDA is based on positive data from the PF708-301 Phase III clinical trial, which showed overall comparable profiles in osteoporosis patients with Forteo.

Flexion’s Zilretta for Osteoporosis of the Knee

Flexion Therapeutics has a target action date of October 14 for its supplemental NDA to revise the label for Zilretta to allow for repeat administration. This sNDA was based on an open-label Phase IIIb clinical trial of Zilretta in patients with osteoarthritis (OA) of the knee. It showed that repeat dosing of the drug for OA knee pain was generally safe and well-tolerated with no deleterious impact on cartilage or joint structure as seen on x-rays. The trial also found that the amount and duration of pain relief was similar in the first and second injections.

Zilretta launched in the fourth quarter of 2017. It is the first and only extended-release, intra-articular therapy for OA-related knee pain. It uses the company’s proprietary microsphere technology combined with triamcinolone acetonide, a common short-acting corticosteroid with a poly lactic-co-glycolic acid (PLGA) matrix that provides extended pain relief.

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Alexion Pharmaceuticals’ Ultomiris for aHUS

Alexion Pharmaceuticals has a target action date of October 19 for its supplemental Biologics License Application (sBLA) for Ultomiris (ravulizumab-cwvz) for the treatment of atypical hemolytic uremic syndrome (aHUS) in order to inhibit complement-mediated thrombotic microangiopathy (TMA). aHUS is a severe and chronic ultra-rare disease that can cause progressive damage to the organs, primarily the kidneys, which can lead to kidney failure and premature death.

Ultomiris is approved to treat adults with Paroxysmal Nocturnal Hemoglobinuria (PNH).

The sBLA is based on data from the Phase III trial of the drug announced in January 2019. In the first 26-week treatment period, 53.6% of patients showed complete thrombotic microangiopathy (TMA) response. The primary endpoint of complete TMA response was defined by hematologic normalization and improved kidney function.

The sBLA is being evaluated under Priority Review.

Clearside Biomedical’s Xipere for Macular Edema

Clearside Biomedical has a target action date of October 19 for its NDA for Xipere (triamcinolone acetonide ophthalmic suspension) for Suprachoroidal Injection for macular edema associated with uveitis. The NDA is based on data from the PEACHTREE clinical trial that showed significant and clinically meaningful improvement in eyesight for patients with macular edema associated with non-infectious uveitis. Uveitis is a group of ocular inflammatory conditions and one of the leading causes of vision loss. It affects about 350,000 people in the U.S. and more than a million worldwide. Macular edema is an accumulation of fluid in the macula, the area of the retina that accounts for sharp, straight-ahead vision.

However, on August 22, the company received an update about the NDA from the FDA’s Office of Pharmaceutical Quality (OPQ) requesting more stability data for the TA suspension that uses an enhanced manufacturing process. The TA formulation hadn’t changed, but the OPQ requested data to verify comparability of the stability profiles from several batches submitted as part of the NDA.

As a result, the company expects to receive a Complete Response Letter from the FDA on or before October 19. It will then resubmit the NDA in the first quarter of 2020 with the requested stability data.

“We believe this is primarily a timing issue since our stability data from previously manufactured batches have been consistent and predictable, and we have every reason to believe this will continue to be the case,” stated George Lasezkay, Clearside’s chief executive officer, in an August statement.

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