The U.S. Food and Drug Administration (FDA) is considering a new drug application for FX006 for treating pain in patients with knee osteoarthritis (OA). The agency is also revisiting the labeling of medications containing pioglitazone, which has been linked to bladder cancer. And new labeling for the HIV drug Genvoya will remove warnings regarding bone loss.
New Drug Application for FX006 with FDA
A new drug application has been submitted to the FDA for FX006 (Zilretta), a long-acting steroid injection for knee OA.1 The treatment combines triamcinolone acetonide (TCA) in a polymer to provide longer lasting pain relief.
In a Phase 3 trial, patients who received FX006 reported about half of the pain level on average compared with placebo-treated patients through 12 weeks.2 This study was a Phase 3, randomized, double-blind, placebo-controlled, active-comparator trial. Efficacy was assessed in 484 patients at four-week intervals over 24 weeks. The primary trial endpoint was pain reduction assessed by the weekly mean of the average pain score for active comparator compared with placebo, which was achieved by FX006 (P<0.0001).
The treatment also achieved statistically significant improvements in WOMAC A (pain), B (stiffness) and C (function) at Weeks 4, 8 and 12 compared with placebo and immediate-release TCA (P<0.05). Efficacy by Knee Injury and Osteoarthritis Outcome Score quality of life at four-week intervals over 24 weeks was also achieved by FX006.
Adverse events were mild and balanced across treatment and placebo study arms. No serious adverse events occurred.
Pioglitazone Linked to Bladder Cancer Risk
In September 2010 and June 2011, based on interim results from a 10-year epidemiologic study, the public and medical communities were alerted to the possible risk of bladder cancer from the use of medications containing pioglitazone. Label changes occurred in August 2011 to include this risk. At the time, manufacturers were required to continue the study. Now as a result of an updated review, the FDA has concluded that the use of medications containing pioglitazone (e.g., Actos, Actoplus Met, Actoplus Met XR, Duetact, Oseni) may have an increased risk of bladder cancer.3
The FDA reviewed published epidemiological studies evaluating the risk of bladder cancer with pioglitazone use. Some studies found an increased risk of bladder cancer with using pioglitazone, while others did not. The labeling for pioglitazone-containing medicines will be updated to include additional studies that describe the risk.
Patients should be informed to contact their healthcare professionals if they experience any of the following signs or symptoms, which may be due to bladder cancer, after starting pioglitazone: blood or red colored urine, urination pain, and/or a new or worsening urge to urinate. Healthcare providers should not proscribe pioglitazone for patients with active bladder cancer. Additionally, the use of medications containing pioglitazone in patients with a history of bladder cancer should be weighed carefully before being prescribed.
HIV Drug Gets New Labeling
Initially, FDA labeling for Genvoya (150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine and 10 mg tenofovir alafenamide tablets) stated that a bone mineral density (BMD) assessment should be considered by any patients treated with Genvoya—especially patients with a history of pathologic bone fracture, other risk factors for bone loss or osteoporosis. Additionally, patients who received products containing tenofovir disoproxil fumarate were at risk for developing hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy. However, at the time, these effects were not yet known for Genvoya.
The FDA has now posted updated prescribing information for Genvoya, which have removed the warnings regarding bone loss.4 Both of these statements have been removed from the Warnings and Precautions section. Genvoya labeling has also been updated with longer-term safety, efficacy and resistance data from 96 weeks of treatment in adults with mild to moderate renal impairment.
Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
References
- Stendahl M. Fast-growing Burlington biotech Flexion files for approval of lead drug. Boston Business Journal. 2016 Dec 12.
- Flexion Therapeutics Inc. News release: Flexion Therapeutics announces presentation of Phase 3 data demonstrating that extended-release Zilretta achieves clinically significant improvement of pain, stiffness and function in patients with osteoarthritis of the knee. 2016 Nov 11.
- U.S. Food and Drug Administration. FDA drug safety communication: Updated FDA review concludes that use of type 2 diabetes medicine pioglitazone may be linked to an increased risk of bladder cancer. 2016 Dec 12.
- Ernst D. Updated labeling for combo HIV drug Genvoya. MPR. 2016 Dec 12.
