Nuwiq®: Clinical safety profile demonstrated in clinical trials

Clinical safety profile observations in 135 Previously Treated Patients (PTPs) across 5 clinical studies

Reported ADRs in clinical trials in 135 PTPs with severe hemophilia A

MedDRA Standard System Organ Class	Adverse reactions	Frequency*
Nervous system disorders	Paresthesia, Headache†	Uncommon
General disorders and administration site conditions	Injection site inflammation Injection site pain	Uncommon
Investigations	Non-neutralizing antibodies positive (without inhibitory activity as measured by the modified Bethesda assay)	Uncommon
Musculoskeletal and connective tissue disorders	Back pain†	Uncommon
Ear and labyrinth disorders	Vertigo	Uncommon
Gastrointestinal disorders	Dry mouth	Uncommon

* Uncommon = frequency between 1/100 and 1/1000
† ADR in a pediatric patient.
ADR = Adverse drug reaction; MedDRA = Medical dictionary for regulatory activities
Adapted from Nuwiq Product Monograph

A non-neutralizing anti-FVIII antibody was detected in one adult patient at completion visit. The sample was tested by the central laboratory at eight dilutions. The result was positive only for undiluted sample and the antibody titre was very low. Inhibitory activity, as measured by the modified Bethesda assay, was not detected in this patient. Clinical efficacy and IVR of Nuwiq® were not affected in this patient.

Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have rarely been observed with FVIII preparations and may in some cases progress to severe anaphylaxis (including shock).

Warnings and Precautions

Sensitivity/Resistance

As with any intravenous protein product, allergic-type hypersensitivity reactions are possible. Patients must be closely monitored for any suggestive symptoms throughout the infusion period.

Patients should be informed of the early signs of hypersensitivity reactions, including rash, hives, urticaria, swelling of lips and tongue, difficulty breathing, wheezing, tightness of the chest, dizziness and syncope. These symptoms can constitute an early sign of an anaphylactic shock. Patients should be advised to stop the injection if any of these symptoms arise and contact their physician. Severe symptoms require prompt emergency treatment.

In case of shock, the current medical standards for treatment of shock should be observed.

Inhibitors

The formation of neutralizing antibodies (inhibitors) to FVIII is a known complication of the management of individuals with hemophilia A. These antibodies inhibit the action of the infused FVIII, which results in insufficient clinical response. Inhibitor development is greatest in previously untreated patients (PUPs) and during the first 20-50 exposure days (EDs). Inhibitors may also develop when switching between different FVIII preparations.

All patients treated with Nuwiq® should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests (see Monitoring and Laboratory Tests).

In the clinical studies (n=135) conducted with Nuwiq® no inhibitors were detected in previously treated adult or pediatric patients with severe hemophilia A.

A study in previously untreated patients (PUPs) assessing the immunogenicity of Nuwiq® is ongoing. In the pre-planned interim analysis of this study, eleven (12.9%) of the 85 patients who received Nuwiq® and had at least one inhibitor test after exposure day (ED) 1 developed high-titre inhibitors and seven (8.2%) developed low-titre inhibitors.

safety information

Indications and clinical use

Nuwiq® is indicated for the treatment and prophylaxis of bleeding in patients of all ages suffering with hemophilia A (congenital factor VIII deficiency).

Nuwiq® is also indicated for the peri-operative treatment of hemophilia A patients.

Pediatrics (< 12 years of age): Half-life (T1/2) and incremental in vivo recovery (IVR) are slightly lower in children than in adults and clearance is slightly higher. Efficacy in prophylaxis and the treatment of bleeds is comparable between children and adults. Data indicate that Nuwiq® is equally efficacious and safe in this population.

Contraindications

Nuwiq® is contraindicated for patients who are hypersensitive to the active substance or to any ingredient in the formulation or component of the container.

Relevant warnings and precautions

It is essential to confirm the deficiency of FVIII before starting treatment with Nuwiq®.
Nuwiq® powder should be reconstituted according to directions and using only the supplied solvent (2.5 mL water for injection) and the supplied injection set to ensure optimal effectiveness and safety.
Transmission of infectious viruses can result from use of contaminated needles or accidental puncture with contaminated needles.
Strongly recommended that every time Nuwiq® is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
All patients treated with Nuwiq® should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests
Allergic-type hypersensitivity reactions are possible.
Risk of central venous access device (CVAD)-related complications.
Do not use this medicine after the expiry date stated on the label or if signs of deterioration of the tamper-proof packaging, especially of the syringe and/or the vial, are visible.
Pregnant and Nursing Women: animal reproduction studies have not been conducted with Nuwiq® and it has not been used in women. Nuwiq® should be used during pregnancy and lactation only if clearly indicated.

For more information

Please consult the product monograph at https://www.octapharma.ca/en/therapies/product-overview/ for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed on this site. The product monograph is also available by calling us at 1-888-438-0488 or by contacting us via email: medinfo@octapharma.ca

Adverse Event Reporting

Health professionals may report adverse reactions to adr.canada@octapharma.com. You can also report any suspected Adverse Reactions directly to the Canada Vigilance Program (https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html).