ADZYNMA is the first and only FDA-approved recombinant ADAMTS13 therapy for patients with congenital thrombotic thrombocytopenic purpura (cTTP) designed to address its root cause.1*
*ADAMTS13 enzyme deficiency.2,3
†In a PK analysis of a clinical study, ADZYNMA was shown to increase the levels of ADAMTS13.1
ADZYNMA (ADAMTS13, recombinant-krhn) is indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).
ADZYNMA was studied in a global prospective, randomized, active-controlled, open-label, two-period crossover study followed by a single-arm continuation period (Study 1) evaluating the efficacy and safety of the prophylactic and on-demand enzyme replacement therapy with ADZYNMA compared to plasma-based therapies in patients with cTTP. In the prophylactic efficacy and safety evaluation, patients received ADZYNMA 40 IU/kg weekly or every other week or plasma-based therapy for 6 months (Period 1), then crossed over to the other treatment for 6 months (Period 2). All patients received ADZYNMA for the single arm continuation period (Period 3).1 cTTP is an ultra-rare disease with ADAMTS13 genetic mutations leading to ADAMTS13 deficiency.2,3
ADZYNMA is a recombinant form of the endogenous ADAMTS13.
Compared to plasma-based therapies:
‡Cmax, AUC
§Cave
| Parameter (unit) |
Mean (SD) Min; Max (N=23) |
|---|---|
|
Cmax (IU/mL) |
1.15 (0.25) 0.78; 1.56 |
|
AUC0-inf (IU*h/mL) |
57.6 (13.9) 37.0; 88.2 |
|
AUC(0-168 h) (IU*h/mL) |
57.2 (13.67) 36.2; 87.2 |
|
Cave(0-168 h) (IU*h/mL) |
0.30 (0.07) 0.20; 0.46 |
|
Duration ADAMTS13 Activity above 10% (days) |
5.8 (1.2) 4.5; 8.9 |
AUC = area under ADAMTS13 activity-time curve; Cave (0-168 h) = average
ADAMTS13 activity from 0 to 168 hours dosing interval; Cmax = maximum ADAMTS13 activity.
Note: 1 IU/mL ADAMTS13 activity corresponds to 100% average normal activity.
SD = standard deviation.
In Periods 1 and 2:
No acutea or subacutec TTP events were reported in patients receiving ADZYNMA (n=37). In patients receiving plasma-based therapies (n=38), one acute TTP event occurred in a patient and five subacute events were reported in four patients.
Mean annualized event rate of thrombocytopeniad was 2.0 in patients receiving ADZYNMA as compared to 4.44 in patients receiving plasma-based therapies.
Mean annualized event rate of microangiopathic hemolytic anemiad was 0.38 in patients receiving ADZYNMA as compared to 1.47 in patients receiving plasma-based therapies.
| ADZYNMA N=37 |
Plasma‑Based Therapies N=38 |
|
|---|---|---|
| Acute TTP eventsa | ||
| Number of subjects with event | 0 | 1 |
| Mean annualized event rate (SD)b | 0 (0.000) | 0.05 (0.304) |
| Subacute TTP eventsc | ||
| Number of subjects with event | 0 | 4 |
| Mean annualized event rate (SD)b | 0 (0.000) | 0.27 (0.836) |
| TTP manifestationsd | ||
| Thrombocytopenia eventse | ||
| Number of subjects with event | 9 | 19 |
| Mean annualized event rate (SD)b | 2.0 (4.706) | 4.44 (6.312) |
| Microangiopathic hemolytic anemia eventsf | ||
| Number of subjects with event | 5 | 11 |
| Mean annualized event rate (SD)b | 0.38 (1.028) | 1.47 (3.274) |
SD = standard deviation; TTP = thrombotic thrombocytopenic purpura
bAnnualized event rate for a subject = number of events/duration of the observation period (years). Data shown are non‑model based.
dTTP manifestations not shown also included renal dysfunction, neurological symptoms and abdominal pain. The clinical significance of the observed difference for the presented manifestations is unknown.
For definitions of Acute and Subacute events, as well as Thrombocytopenia and Microangiopathic Hemolytic Anemia events, please click here click here
The safety profile of ADZYNMA was evaluated in Study 1.
PBT, plasma-based therapy.
| Adverse Reaction |
(N=48) n (%)a |
|---|---|
| Headache | 15 (31.3) |
| Diarrhea | 8 (16.7) |
| Migraine | 7 (14.6) |
| Abdominal pain | 6 (12.5) |
| Nausea | 6 (12.5) |
| Upper respiratory tract infection | 6 (12.5) |
| Dizziness | 5 (10.4) |
| Vomiting | 5 (10.4) |
N = Total number of patients treated with ADZYNMA in Study 1.
n = Number of patients who had at least one event in the category.
aPercentages by patient were calculated using the number of all subjects who had the listed adverse event.
Recommended prophylactic dosage regimen of ADZYNMA is as follows:
For on-demand treatment of an acute event:
| Treatment Day 1 | Treatment Day 2 | Treatment Day 3 and Beyond |
|---|---|---|
| 40 IU/kg | 20 IU/kg | 15 IU/kg once daily until two days after the acute event is resolved. |
ADZYNMA is a lyophilized powder in single-dose vials containing nominally 500 or 1500 International Units (IU) per vial and comes with 5 mL of Sterile Water for Injection.
Infusing ADZYNMA 40 IU/kg would take approximately 2.5-5 minutes for a 70 kg patient (rate 2 to 4 mL per minute) utilizing the 1500 IU vials.
Get a step-by-step look at how to reconstitute and administer ADZYNMA for your patients.
For full reconstitution and administration instructions, please refer to the Instructions for Use in the ADZYNMA full Prescribing Information.
Courtney: Hi, my name is Courtney. I’m going to show you how to reconstitute ADZYNMA and administer it to your patients.
Courtney: As ADZYNMA is administered by intravenous injection, it’s important to use aseptic technique (clean and germ free) throughout the procedure.
Courtney: Before we start, we need to wash and dry our hands thoroughly and put on clean exam gloves.
Courtney: First, let’s prepare a clean, germ-free, flat surface and gather all the materials needed for reconstitution and administration.
Courtney: Materials for reconstitution.
Courtney: Materials for administration.
Courtney: Check the expiration date on the vial or carton of ADZYNMA and do not use if the expiration date has passed or if not stored properly.
Courtney: Allow the vials to reach room temperature before use.
Courtney: Now we’re ready to prepare ADZYNMA for injection. Remove the plastic caps from the ADZYNMA and diluent vials and place them on a flat surface.
Courtney: Wipe the rubber stoppers on the top of the vials with an alcohol swab and let them dry.
Courtney: Next, open the BAXJECT II Hi-Flow device by peeling away the lid, being careful not to touch the inside of the pack.
Courtney: Turn the package with the BAXJECT II Hi-Flow device upside down and place it over the top of the diluent vial.
Courtney: Press it straight down until the clear plastic spike pierces the stopper of the diluent vial.
Courtney: Grip the BAXJECT II Hi-Flow device package at its edge and pull the package off the device.
Courtney: For the next step, we need to turn the system over so that the diluent vial is on top. Press the BAXJECT II Hi-Flow device straight down until the purple plastic spike pierces the ADZYNMA powder vial stopper.
Courtney: The vacuum will draw the diluent into the vial containing ADZYNMA powder. You may notice some bubbles or foam; this is normal and should soon disappear. Wait until bubbles or foam dissipate before administration.
Courtney: Now swirl the connected vials gently and continuously until the ADZYNMA powder is completely dissolved. It is important not to shake the vial.
Courtney: Before administering ADZYNMA, inspect the reconstituted solution visually for any particulate matter or discoloration. The solution should be clear and colorless.
Courtney: Do not use the solution if you see any particulate matter or discoloration.
Courtney: Once reconstituted, you should use ADZYNMA within 3 hours and keep at room temperature. Do not store at any other temperature. Discard any unused product if not used within 3 hours after reconstitution.
Courtney: We are now ready to administer ADZYNMA. Let’s go through these steps together.
Courtney: Take off the blue cap from the BAXJECT II Hi-Flow device and attach a Luer-lock syringe, without injecting air into the system. Turn the system upside down so the solution for infusion is at the top (ADZYNMA vial is now on top).
Courtney: Draw the solution into the syringe by pulling the plunger back slowly.
Courtney: If the dose you need for your patient requires more than one vial of ADZYNMA, you will need to reconstitute each vial according to the instructions provided earlier in this video.
Courtney: You will need to use a different BAXJECT II Hi-Flow device to reconstitute each vial.
Courtney: Additional vials of reconstituted product can be drawn into the same syringe to avoid administering multiple injections. Reconstitute each vial using a new BAXJECT II Hi-Flow device each time, and draw the product into the syringe until the total volume to be administered is reached.
Courtney: Disconnect the syringe and attach a suitable injection needle or infusion set. To remove any air bubbles, point the needle upwards and gently tap the syringe with your finger.
Courtney: Slowly and carefully push the air out of the syringe and needle.
Courtney: Now we are ready to administer ADZYNMA.
Courtney: First, apply a tourniquet to your patient’s arm and clean the chosen infusion site with an alcohol swab.
Courtney: Insert the needle into your patient’s vein and remove the tourniquet. ADZYNMA should be infused slowly, at a rate of 2 to 4 milliliters per minute. You may want to use a syringe pump to control the rate of infusion.
Courtney: Once administration is complete, remove the needle from the vein and put pressure on the infusion site with a cotton ball or gauze for several minutes to stop bleeding.
Courtney: Do not recap the needle. Place the needle, syringe, and vials in a puncture-resistant sharps container.
Courtney: Vials are for single use only and any remaining solution must be discarded in accordance with local requirements.
Courtney: That completes the reconstitution and administration of ADZYNMA.
Courtney: I hope this has been helpful. Thank you for joining me today.
Courtney:
ADZYNMA (ADAMTS13, recombinant-krhn) is indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).
WARNING: NEUTRALIZING ANTIBODIES TO ADAMTS13
ADZYNMA is contraindicated in patients who have experienced life-threatening hypersensitivity reactions to ADZYNMA or its components.
Neutralizing Antibodies: Neutralizing antibodies to ADAMTS13 with serious outcomes including death have occurred following ADZYNMA administration. Neutralizing antibodies may result in a decreased or lack of response to recombinant or plasma-derived ADAMTS13 which could lead to serious disease related outcomes. Neutralizing antibodies were not reported in the cTTP clinical trials. All subjects had been previously exposed to ADAMTS13 through plasma-based products. There are no data on immunogenicity with ADZYNMA in previously untreated patients (subjects naïve to plasma-based products).
Monitor all patients, including those who were previously exposed or naïve to plasma-based products, by assessing ADAMTS13 activity and ADAMTS13 neutralizing antibodies prior to initiation of ADZYNMA and periodically during the course of treatment. If expected ADAMTS13 activity levels are not attained or if acute TTP exacerbation occurs despite appropriate dose, perform an assay that measures ADAMTS13 neutralizing antibody concentrations. Laboratory tests for monitoring neutralizing antibody levels are not capable of distinguishing between inhibitors directed against ADZYNMA, the patient’s endogenous ADAMTS13, or ADAMTS13 from other plasma sources.
Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, may occur with ADZYNMA. Monitor patients for signs and symptoms of hypersensitivity reactions which may include tachycardia, chest tightness, wheezing and/or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and restlessness. If signs and symptoms of severe hypersensitivity reactions occur, immediately discontinue administration of ADZYNMA and provide appropriate supportive care.
Adverse Reactions: The most commonly observed adverse reactions (>5% of subjects) associated with ADZYNMA are headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness and vomiting.
Use in Specific Populations: The safety of ADZYNMA for use during pregnancy has not been established in controlled clinical trials. Limited data are insufficient to inform a drug associated risk of adverse developmental outcomes. There is no information regarding the presence of ADZYNMA in human milk, its effects on milk production, or the breastfed infant.
To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please click for Full Prescribing Information.
This brochure is a helpful guide that explains cTTP, how ADZYNMA can help, and what to expect.
aAcute TTP events were defined in protocol by a drop in platelet count (≥50% of baseline or a platelet count <100,000/µL) and an elevation of lactate dehydrogenase (LDH) (>2× baseline or >2× upper limit normal (ULN)).
cSubacute events were defined by a thrombocytopenia event or a microangiopathic hemolytic anemia event; and organ‑specific signs and symptoms including but not limited to renal dysfunction events, neurological symptoms events, fever, fatigue/lethargy, and/or abdominal pain.
eThrombocytopenia events were defined as a drop in platelet count ≥25% of baseline or a platelet count <150,000/µL.
fMicroangiopathic hemolytic anemia events were defined as an elevation of LDH >1.5×baseline or >1.5 ×ULN.
Indication & Important Safety Information including Boxed WARNING for Neutralizing Antibodies to ADAMTS13
WARNING: NEUTRALIZING ANTIBODIES TO ADAMTS13
ADZYNMA is contraindicated in patients who have experienced life-threatening hypersensitivity reactions to ADZYNMA or its components.
Neutralizing Antibodies: Neutralizing antibodies to ADAMTS13 with serious outcomes including death have occurred following ADZYNMA administration. Neutralizing antibodies may result in a decreased or lack of response to recombinant or plasma-derived ADAMTS13 which could lead to serious disease related outcomes. Neutralizing antibodies were not reported in the cTTP clinical trials. All subjects had been previously exposed to ADAMTS13 through plasma-based products. There are no data on immunogenicity with ADZYNMA in previously untreated patients (subjects naïve to plasma-based products).
Monitor all patients, including those who were previously exposed or naïve to plasma-based products, by assessing ADAMTS13 activity and ADAMTS13 neutralizing antibodies prior to initiation of ADZYNMA and periodically during the course of treatment. If expected ADAMTS13 activity levels are not attained or if acute TTP exacerbation occurs despite appropriate dose, perform an assay that measures ADAMTS13 neutralizing antibody concentrations. Laboratory tests for monitoring neutralizing antibody levels are not capable of distinguishing between inhibitors directed against ADZYNMA, the patient’s endogenous ADAMTS13, or ADAMTS13 from other plasma sources.
Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, may occur with ADZYNMA. Monitor patients for signs and symptoms of hypersensitivity reactions which may include tachycardia, chest tightness, wheezing and/or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and restlessness. If signs and symptoms of severe hypersensitivity reactions occur, immediately discontinue administration of ADZYNMA and provide appropriate supportive care.
Adverse Reactions: The most commonly observed adverse reactions (>5% of subjects) associated with ADZYNMA are headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness and vomiting.
Use in Specific Populations: The safety of ADZYNMA for use during pregnancy has not been established in controlled clinical trials. Limited data are insufficient to inform a drug associated risk of adverse developmental outcomes. There is no information regarding the presence of ADZYNMA in human milk, its effects on milk production, or the breastfed infant.
To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please click for Full Prescribing Information.
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