Regulatory Decision Summary for HyQvia

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.


Product type:

Drug

Medicinal ingredient(s):

Hyaluronidase (Human Recombinant), Immunoglobulin (Human)

Therapeutic area:

J06

Type of submission:

New Drug Submission (New Active Substance)

Control number:

247727
What was the purpose of this submission?

HyQvia (Normal Immunoglobulin [Human] 10% and Recombinant Human Hyaluronidase) is a new combination product for the treatment of primary and secondary humoral immunodeficiencies. The product is presented as two vials, one containing antibodies (immunoglobulin or IG 10%) solution for infusion. The second vial contains recombinant human hyaluronidase PH20 (rHuPH20), an enzyme which facilitates the subcutaneous infusion of IG 10%.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway

After evaluation of the information provided for safety, efficacy and pharmacokinetics requirements, Health Canada has authorized the marketing of HyQvia for the following indications:

  • HyQvia is indicated as replacement therapy for primary humoral immunodeficiency and secondary humoral immunodeficiency in adult patients.

Why was the decision issued?

HyQvia is administered in a two-step process, with first the pre-infusion of rHuPH20 followed by the infusion of IG 10% through the same needle-infusion set. By temporarily degrading locally the hyaluronan molecules under the skin, rHuPH20 allows patients to tolerate large volumes of IG 10% infused subcutaneously. The dose of IG 10% provides sufficient antibodies in the blood stream for a dosing interval once every three or four weeks.

The efficacy of HyQvia was demonstrated in 68 patients with primary humoral immunodeficiency who completed a clinical study that had initially enrolled 87 patients aged between 4 to 78 years with only 8 patients aged less than 16 years. HyQvia was shown to maintain a low annual rate of serious bacterial infections that was comparable to the rate observed following intravenous infusion. The secondary immune deficiency indication was accepted based on evidence in primary humoral immunodeficiency patients. The safety of HyQvia was demonstrated during four clinical studies in a total of 82 adult patients with primary humoral immunodeficiencies. Since the IG 10% component of HyQvia is prepared from large pools of human plasma, there is a residual risk that it may contain causative agents of viral or other undetermined diseases despite donor screening and effective inactivation and removal of viruses during manufacturing. In patients with pre-existing risk factors, other known risks associated with the use of IG infusion products included thromboembolic events, renal failure and transfusion-related acute lung injury and aseptic meningitis syndrome.

Risks related specifically to HyQvia include local infusion site adverse events following subcutaneous infusion of both rHuPH20 and IG 10% (e.g. pain, edema, swelling) that are considered temporary reactions. There is also the risk in spreading existing skin infections and possible contamination of the needle infusion set or administration errors. Although the safety in the long-term use of rHuPH20 is unknown, including uncertainties associated with the development of high levels of anti-rHuPH20 antibodies in circulation, non-clinical studies in animals support the safe use of HyQvia in humans at the recommended therapeutic dose. Due to the limited number of pediatric patients evaluated during the pivotal study (8 patients less than 16 years), safety was not adequately demonstrated in pediatrics to grant an indication in this age group at this time. Concerns reside in the safety with the chronic use of rHuPH20 as well as possible intolerance of large volumes of IG% infused particularly in small infants and neonates.

The benefit in the use of HyQvia is considered favorable over the risks, with risk mitigations described in the proposed Product Monograph. It is recommended that only patients and caregivers pre-trained in the use of this product may self-administer HyQvia at home. A Notice of Compliance (NOC) was issued.

A Risk Management Plan (RMP) for HyQvia was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for HyQvia has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

For further details about HyQvia, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.

Decision issued

Authorized; issued a Notice of Compliance (NOC) in accordance with the Food and Drug Regulations.