FDA Action Alert: Avenue/Fortress and Alexion


Although October doesn’t appear to be a very busy month for the U.S. Food and Drug Administration (FDA)’s PDUFA dates, there are a few. Here’s a look at the next two weeks.

Avenue Therapeutics and Fortress Biotech’s IV Tramadol After Abdominoplasty Surgery

Avenue Therapeutics has a target action date of October 10, 2020, for its New Drug Application (NDA) for IV tramadol in patients following abdominoplasty surgery, specifically, and for management of moderate to moderately severe pain in adults in a medically-supervised health care setting.

In June, the company announced the publication of Phase III trial data in several scientific journals. Data published in Drugs in R&D described the Phase III trial to evaluate IV tramadol 50 mg compared to placebo in patients after abdominoplasty surgery, a soft-tissue surgical model. The trial included an active comparator arm, IV morphine 4mg. It wasn’t powered to provide statistical comparison of the two active arms, but its sample size provided an assessment of the general comparability of the two treatment regimens. The data demonstrated that IV tramadol was statistically superior to placebo and comparable to IV morphine for the primary and all key secondary outcomes. IV tramadol also had numerically lower incidences of the most common treatment-emergent events than IV morphine.

The second was published in Substance Abuse: Research and Treatment. The study analyzed the rates of misuse of products containing oral tramadol, a Schedule IV opioid, compared to comparator Schedule II opioids, such as morphine, oxycodone, and hydrocodone, and alprazolam, a commonly prescribed Schedule IV controlled substance in the U.S. The data demonstrated a low prevalence of oral tramadol misuse compared to other prescribed opioids, as well as less than alprazolam.

On September 9, the company published more data in the Journal of Opioid Management, which reviewed the pharmacokinetics of IV tramadol dosing regimen intended for the U.S.

Alexion Pharmaceuticals’ Higher Dose Ultomiris

Alexion Pharmaceuticals has a target action date of October 11 for its 100mg/mL dose of Ultomiris. Ultomiris is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults and for adults and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS). PNH is a rare blood disease that results in red blood cells breaking apart. aHUS primary affects kidney function, can occur at any age, and causes abnormal blood clots to form in the small blood vessels in the kidneys.

On September 21, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending marketing authorization in Europe for the new 100 mg/mL IV formulation of Ultomiris. This dosage would reduce average annual infusion times by about 60% compared to the 10 mg/mL dosage while offering comparable safety and efficacy. That, the company claims, means patients would spend six hours or less a year receiving treatment.

“The advanced formulation of Ultomiris marks continued progress in Alexion’s ongoing efforts to innovate for patients, and we expect it will represent yet another step in refining the treatment schedule for patients,” said John Orloff, executive vice president and head of Research & Development at Alexion. “Importantly, it would mean that most patients would spend only six hours or less a year receiving treatment, allowing them to focus on other aspects of their lives.”

The CHMP opinion was based on a comprehensive chemistry, manufacturing and control submission and a supplementary clinical data set demonstrating that the safety, pharmacokinetics and immunogenicity of the two different doses were comparable. There was no notable effect in the efficacy measure of mean lactate dehydrogenase (LDH) levels across the formulations. The new formulation would cut the infusion time to 25 to 75 minutes depending on body weight compared to 77 to 194 minutes on the 10 mg/mL formulation.

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