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FDA Panel Reviews Long-Term Safety of Immune Therapy HyQvia

Agency questions risk of inflammation and fertility problems

On the morning of July 31, the FDA’s Blood Products Advisory Committee met to discuss the biologics license application for HyQvia (immune globulin infusion 10% [human]; Baxter Healthcare Corp.) combined with recombinant human hyaluronidase (rHuPH20) for the treatment of patients with primary immune deficiency.

Specifically, the panel looked at whether the benefits of the treatment outweigh its risks, with a focus on immunogenicity. The FDA is not obligated to follow the recommendations of its advisors but usually does so.

The FDA declined to approve HyQvia in July 2012, and asked for more data on its possible adverse effects after 15 out of 83 patients in the clinical trial program developed non-neutralizing antibodies against rHuPH20, which Baxter had licensed from Halozyme Therapeutics Inc. HyQvia was approved in Europe in May 2013.

To address the concern about life-long exposure to anti-rHuPH20 antibodies, the FDA advised Baxter to propose an appropriate animal study, an adequate post-marketing commitment, a label warning, or other strategies.

In its recommendations, the FDA noted: “The risk-benefit considerations are very different for HyQvia compared to other [immunoglobulin] products because the main immunogenetic component of concern (rHuPH20) is not a life-saving therapeutic.” The agency noted that the benefit of the product is primarily one of convenience.

The FDA was particularly concerned that long-term treatment could cause inflammation of the brain and bowel, as well as fertility problems.

Baxter formally submitted data to address the FDA’s questions in November and December 2013. This information included proposed risk-mitigation measures, such as revised labeling, the commitment to perform a life-long toxicology study and a post-marketing safety study, and the creation of a pregnancy registry.

HyQvia is a combination product in a dual-vial unit composed of one vial of immune globulin infusion 10% (human) and one vial of rHuPH20. The two components are administered subcutaneously sequentially through the same needle.

The immune globulin component of HyQvia is identical to Gammagard Liquid IGIV (Baxter), which was licensed by the FDA in April 2005.

rHuPH20 is a recombinant human hyaluronidase that acts locally and transiently within the subcutaneous space, resulting in decreased resistance to fluid flow and a transient increase in the permeability of the local subcutaneous tissue. These effects allow the immune globulin component of HyQvia to disperse through the subcutaneous tissue matrix and results in more immune globulin reaching the systemic circulation.

Current immune globulin therapies are administered intravenously once every 3 to 4 weeks in a hospital, or by injection at home once every 1 to 2 weeks. HyQvia is designed to be injected subcutaneously at home once every 3 to 4 weeks.

Sources: FDA Issue Summary; July 31, 2014; Briefing Document; July 31, 2014; and Reuters; July 30, 2014.

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