FDA Expands Aprepitant Approval For MEC

GINA COLUMBUS @ginacolumbusonc
Wednesday, October 23, 2019
The FDA has expanded the approval of aprepitant (Cinvanti) injectable emulsion for intravenous (IV) use to include the 130-mg single-dose regimen for patients receiving moderately epigenetic chemotherapy (MEC).

The label expansion standardizes the aprepitant 130 mg single-dose regimen for patients receiving highly emetogenic cancer chemotherapy (HEC) and/or MEC as an injection over 2 minutes or an infusion over 30 minutes, which eases the dosing and administration and eliminates the need to take oral aprepitant on days 2 and 3 following MEC administration.

The expansion also builds on the prior label expansion that introduced the 2-minute IV push, which enables physicians to utilize the operational advantages of this administrative method of and contributes to a reduction in total patient time spent at the infusion site, according to Heron Therapeutics, Inc., the developer of aprepitant, in a press release.

"This most recent label expansion to offer a simplified dosing regimen for MEC adds to the important advantages Cinvanti provides to patients as the only FDA-approved, IV NK1 RA available as a convenient 2-minute IV push for MEC and HEC," Rudolph M. Navari, MD, PhD, University of Alabama, Birmingham School of Medicine, Division of Hematology and Oncology, stated in a press release. "The simplified dosing in MEC removes the need for patients to take oral aprepitant on days 2 and 3, which can improve compliance and reduce costs. These benefits continue to improve the overall patient experience with Cinvanti."

Aprepitant is a polysorbate 80-free, IV formulation of an NK1 receptor antagonist, which is designed to significantly reduce CINV in both the acute and delayed phases following chemotherapy. The FDA previously approved aprepitant as a 30-minute IV infusion on November 2017, making it the first IV formulation to directly deliver aprepitant (Emend). In February 2019, the FDA has expanded the approval of aprepitant injectable emulsion to include a 2-minute IV use for the prevention of acute and delayed CINV.

The decision of the earlier approval is based on results of a two-part, phase I study that demonstrated bioequivalence and a similar safety profile for patients who received aprepitant as a standard 30-minute IV infusion compared with a 2-minute IV injection, which is also referred to as an IV push.2

Part A of the study randomized 24 patients to receive aprepitant at 130 mg IV via injection over 15 minutes (cohort 1), 5 minutes (cohort 2), or 2 minutes (cohort 3). The primary endpoint was tolerability and safety of single doses of aprepitant across the 3 cohorts. Patients then progressed to Part B of the trial, which was a two-sequence crossover study, following the establishment of acceptable tolerability in cohorts 2 and 3.

In Part B, 50 patients were randomized to receive a 2-minute injection of 130 mg aprepitant at 9 ml/min or a 30-minute infusion at 296 ml/h. The primary endpoint was pharmacokinetics of plasma aprepitant following a single dose as an injection or infusion; secondary endpoints were safety and tolerability. The mean age of patients was 34; 19 patients were female and 31 were male.

Results showed bioequivalence between the 2 administration arms, confirming the short injection as an alternative method to administer aprepitant to patients. The values for area under the curve (AUC)0-last, AUC0-inf and t1/2 were similar between injections and infusions. Additionally, Cmax was higher in patients who received aprepitant via injection than in those who received it via infusion, and Tmax occurred earlier with the injection versus the infusion.

Regarding safety, 8 patients on the injection arm experienced 11 treatment-emergent adverse events (TEAEs; 6 related) versus 9 patients who experienced 14 TEAEs (9 related) in the infusion group. The most prevalent treatment-related TEAEs were headache and fatigue; 1 patient in each arm reported feeling hot ≤30 minutes following treatment.

The initial approval of aprepitant was based on findings from 2 randomized, crossover studies that demonstrated the bioequivalence of aprepitant to fosaprepitant IV for the prevention of acute and delayed CINV following highly emetogenic cancer (HEC) chemotherapy and moderately emetogenic cancer (MEC) chemotherapy.3,4 Specifically, results showed that patients who received aprepitant reported fewer adverse events (AEs) than those who received IV fosaprepitant, including substantially fewer infusion-site reactions.

A version of this article originally appeared on OncLive as, “FDA Approves Single-Dose Aprepitant Regimen for MES”.



References
  1. Heron Announces FDA Approval of Supplemental New Drug Application to Expand CINVANTI® Label for Single-Dose Regimen for Patients Receiving Moderately Emetogenic Chemotherapy (MEC). Heron Therapeutics, Inc. Published October 22, 2019. https://finance.yahoo.com/news/heron-announces-fda-approval-supplemental-123000083.html. Accessed October 22, 2019.
  2. Ottoboni T, Lauw M, Keller MR, Cravets M, Manhard K, Clendeninn N, Quart B. HTX-019 via 2-min injection or 30-min infusion in healthy subjects [published online ahead of print December 21, 2018]. Future Med. doi: 10.2217/fon-2018-0809.
  3. Heron Therapeutics Announces U.S. FDA Approval of CINVANTI (aprepitant) Injectable Emulsion for the Prevention of Acute and Delayed Chemotherapy-Induced Nausea and Vomiting (CINV). Heron Therapeutics. Published November 9, 2017. https://bit.ly/2NyINfA. Accessed February 28, 2019.
  4. Ottoboni T, Boccia G, Keller MR, Cravets M, Clendeninn N, Quart B. Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects. Presented at: 2017 Hematology/Oncology Pharmacy Association Annual Conference; March 29-April 1, 2017; Anaheim, CA.


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