AKYNZEO® injection
Discover the clinical data supporting AKYNZEO injection
The efficacy of AKYNZEO injection was established by demonstrating
- Noninferiority of IV palonosetron bolus vs IV Infusion
- Bioequivalence of fosnetupitant to netupitant
Safety of AKYNZEO injection was established based on:
Palonosetron administered as an IV infusion was shown to be noninferior to a bolus IV push1
- Multicenter, multinational, randomized, double-blind study
- 425 adult cancer patients receiving a non-AC HEC regimen received palonosetron (PALO) plus dexamethasone (DEX) to prevent CINV
- Bolus IV push arm: Single dose of PALO 0.25 mg administered IV over 30 seconds + DEX
- IV infusion arm: Single dose of PALO 0.25 mg administered IV over 30 minutes + DEX
- Primary endpoint: Noninferiority of palonosetron IV infusion to bolus IV push
- Complete response: No emesis or rescue medication use during the acute phase (0-24 hours after chemotherapy)
- Prespecified noninferiority margin was set at -15%
![CR Complete Responce; Dexamethasone, Palonosetron, Oral](/hcp/assets/img/efficacy/complete-response-hec-treated.jpg)
- Patients achieving complete response in the acute phase for IV infusion and IV bolus push were 82.7% and 86.3%, respectively
- Difference of -3.4%; 99% CI -12.0% to 5.2%
- The frequency and severity of all reported TEAEs were similar between treatment arms
Fosnetupitant in AKYNZEO injection demonstrated bioequivalence to netupitant in AKYNZEO capsules1,2
- AKYNZEO injection is the only combination agent that includes a 5-HT3 RA (palonosetron) with an NK-1 RA (netupitant)
- Netupitant, the NK-1 RA in AKYNZEO capsules, is not water soluble, so AKYNZEO injection includes the soluble prodrug, fosnetupitant
- Fosnetupitant is rapidly converted to netupitant after IV administration
Plasma concentrations after single dose of fosnetupitant2
![Plasma Concentration](/hcp/assets/img/efficacy/plasma-concentration.png)
Fosnetupitant plasma concentrations decreased rapidly, while netupitant plasma concentrations remained steady over time2
- The pharmacologic effects of fosnetupitant can be attributed to the activity of netupitant
- An IV fosnetupitant dose of 235 mg (260 mg of fosnetupitant chloride hydrochloride) achieved a similar netupitant area under the curve (AUC) as 300 mg oral netupitant
Linear relationship between fosnetupitant dose and netupitant AUC2
![Linear Relationship between Fosnetupitant dose and Netupitant AUC](/hcp/assets/img/efficacy/rel-fosnet-net.png)
The safety profile of AKYNZEO injection was generally similar to AKYNZEO capsules1,3
- Phase III, multinational, randomized, double-blind, multicycle safety study3
- 404 patients receiving a cisplatin-based HEC regimen for solid tumors received either oral or IV AKYNZEO to prevent CINV1,3
- Median age: 60 years; 46% women; 99.5% white; 0.3% Asian; 0.3% Hispanic1
- Oral arm: Single dose of AKYNZEO capsule + DEX (n=201)
- IV arm: Single IV dose of AKYNZEO + DEX (n=203)
- DEX dose was PO 12 mg on Day 1, followed by 8 mg on Days 2-4 for both arms
- Safety profile was generally similar between oral and IV formulations1,3
- TRAEs were observed in 8.9% and 9.5% of patients in IV and PO arms, respectively
- Severe TRAEs were observed in 0.5% and 1.0% of patients in IV and PO arms, respectively
- There were no infusion-site reactions related to AKYNZEO injection3
AKYNZEO injection contains
- No polysorbate 80
(a solubilizing agent that can cause severe nonimmunologic anaphylactoid reactions)1,4 - No preservatives1
- No soy or egg lecithin1
In clinical trials
- No infusion-site reactions related to AKYNZEO3
- No anaphylaxis attributed to fosnetupitant (NK-1 RA) reported3
- No significant effect on QT interval1
Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving palonosetron, one of the components of AKYNZEO, with or without known hypersensitivity to other 5-HT3 receptor antagonists.
- 5-HT3 RA=5-HT3 receptor antagonist; AC=anthracycline plus cyclophosphamide; CINV=chemotherapy-induced nausea and vomiting; HEC=highly emetogenic chemotherapy; IV=intravenous; NK-1 RA=neurokinin-1 receptor antagonist; PO=oral; TRAE=treatment-related adverse event.
*AKYNZEO injection has not been studied for the prevention of nausea and vomiting associated with AC chemotherapy.