A lead investigator reveals how Baxter's Hyqvia got its hard-won approval
In September, BioPharma Dive reported on the approval of Baxter’s Hyqvia (immunoglobulin infusion 10% with Recombinant Human Hyaluronidase) for treatment of primary immunodeficiency (PI), a collection of roughly 200 different chronic disorders in which the body’s immune system is either missing key components or dysfunctional.
Hyqvia has been hailed as a breakthrough for people who live with PI, because it provides the antibody-based immunoglobulin (IG) that these patients need, while relieving them of the tremendous treatment burden that they have had to live with until now. Traditionally, PI patients have had to have IG treatments several times per week, at different treatment sites. With Hyqvia, they have the option of a treatment regimen that requires only one infusion per month, at one injection site.
The approval of Hyqvia was truly newsworthy, as it became the first FDA-approved subcutaneous (SC) immune globulin (IG) treatment for adult PI that only requires one infusion every three to four weeks, at one injection site.
From a development standpoint, the approval of Hyqvia represents the first approved biologics license application (BLA), which utilizes the rHuPH20 platform.
Gaining approval of Hyqvia—and meeting an unmet medical need—required a dedicated team of clinical investigators. Not only did they design and adhere to a rigorous clinical trial program, but when the FDA rejected Baxter’s first BLA for Hyqvia in April 2012, they prevailed, as Baxter took the necessary steps to provide additional data. Ultimately, this team, lead by Dr. Richard Wasserman, who specializes in immunology, helped usher in a new era of treatment for patients with PI.
BioPharma Dive spoke to Dr. Wasserman to gain insight into PI and how Hyqvia works. He also provided insightful takeaways about strategies for conducting clinical trials and working with the FDA.
BioPharma Dive: What is PI, and considering the fact that there are 200 different conditions, how can it be treated with one approach?
Wasserman: PI basically resolves into two categories: Patients with defective antibody production, which represents 75% of all PI patients, and another group of patients with more heterogeneous white blood cell, broadly based dysfunction. Hyqvia is appropriate for treating patients with defective antibody production-related PI.
People with PI have infections that are more frequent, severe and persistent than people without immune disorders. One important challenge with PI is the need for increased awareness, so that people with undiagnosed PI can live normal, healthy lives. The work of patient-advocacy groups has helped raise awareness among physicians. Twenty years ago, it took more than 10 years to get a diagnosis after the initial onset of symptoms. Now it takes roughly five to six years.
BD: You’ve noted that Hyqvia has helped to address a longstanding unmet medical need. Can you explain more?
Wasserman: In the 1950’s when antibody replacement treatments were introduced, people who required therapy had to endure painful intramuscular injections, and treatments had limited effectiveness. Then in the early 1980’s, intravenous (IV) administration was introduced and became the standard of care, in part, because it was much less painful than intramuscular injections. By the early 2000’s, interest in subcutaneous (SC) treatment options was growing, and in 2005, SC options were introduced in the US. Since then, patients have been able to choose between IV and SC administration, but there have always been drawbacks associated with each mode of administration.
BD: What are the advantages and drawbacks associated with each mode of administration for IG replacement therapy?
Wasserman: IV IG therapy has the advantage of low frequency, meaning it can be given every three to four weeks; however, there is a high rate of side effects—around 25%—including systemic side effects, head ache, muscle aches and fever. In contrast, SC administration has a lower rate of systemic side effects. Also, SC administration is more convenient, because it can be administered from home. However, on the downside, although conventional SC therapy is administered once per week, it requires 8 to 26 needles sticks per month, because patients can only put a certain amount of IG at each site. Patients end up injecting themselves in various parts of their bodies, including their thighs, upper arms, stomach and hips.
BD: How about Hyqvia? How is it different?
Wasserman: Hyqvia allows a patient to receive a full dose of IG in a single site every three to four weeks, with a single needle stick. The recombinant hyaluronidase component enhances the dispersion and absorption of the infusion, making it possible to have only one injection site.
BD: Are there any side effects?
Wasserman: Yes. The rate of systemic side effects in Hyqvia-treated patients is approximately 6% to 9%. Also, there are sometimes infusion site reactions.
BD: Hyqvia was not initially approved by the FDA, but subsequently gained approval. What are some useful take-aways from this experience?
Wasserman: In the Complete Response Letter, the FDA requested more preclinical data. There were concerns about the fact that some patients had developed antibodies to hyaluronidase. However, this was found to be transient. We followed 83 patients for another 1.5 years and found that 5.8% of normal human beings have anti-enzyme antibodies. It simply took more time to figure this out.
The level of scrutiny at the FDA has increased dramatically in the last five years. When considering initiating or participating in a clinical trial, never underestimate the demands. Clinical trial work is a major commitment, but when done properly, committed clinical investigation and rigorous documentation can pave the way for bringing new treatment options to patients.