The hazard is more there than anywhere else, he notes. “But my ultimate nightmare scenario is when, let’s say, a patient who has hemophilia and is on this medication is traveling somewhere, has an auto accident and major trauma, and is perhaps unconscious. They get taken to a trauma center and the center says, ‘Oh my gosh, you have pelvic fractures. We need to do surgery right away.’ The surgeons measure APTT to determine if there is risk for bleeding, but this patient who actually has hemophilia will have normal APTT and will be okayed to have major surgery.”
That’s going to happen, he predicts. “The patient will have surgery, and while emicizumab will offer some level of coagulation protection from bleeding, if it’s a big surgery it’s probably not going to be enough, and there will be significant bleeding during the surgery.”
If the drug becomes as widely used as he expects, “labs need to ask themselves when they are receiving samples if they should alter their requisition form,” Dr. Young says, so that when factor VIII activity level or inhibitor level is ordered, there is a box to check if the patient is on emicizumab. “If the lab is aware whether the patient is on the drug or not, that can help them in ensuring a proper test is done and proper interpretation is done.”
A double check, where a laboratory receives a sample and there is an alert asking if the patient is on emicizumab, is another possible mechanism that might help. “I think that’s something the laboratory societies should be considering,” he says.
The vast majority of hemophilia patients are treated at one of the 140 hemophilia centers in the U.S., Dr. Young says. “But there are some patients outside those centers, and I worry about those patients even more, because doctors may see emicizumab as really useful, and the sales rep will recommend that they put patients on it, which is fine if it’s beneficial to their patients. But the doctors may not be hemophilia or coagulation experts, and that’s where we need to worry even more about misinterpretation of lab results.”
Still, he says, it should not be forgotten that emicizumab is a life-changing drug. One example he cites is the case of a 12 year old who was spending 30 percent of his time in a wheelchair, missing a lot of school, spending a lot of time in the hospital. “Now, since he was put on the drug two-and-a-half years ago, he hasn’t missed any school, he pretty much has no bleeding, he can do all kinds of physical activities, and the family got rid of the wheelchair a long time ago.”
Dr. Young has also seen the same effect on younger patients. “There have been four and five year olds who were bleeding all the time, having a lot of pain, and their families have to do a lot of infusions. Now I have five kids younger than age 12 who have been on the clinical trial of emicizumab an average of two years and none of them has had a bleed at all. They’ve gone from 15 to 20 bleeds a year, pain, damage to joints, and multiple IV infusions to basically being a normal kid and not having to do any infusions other than weekly subcutaneous ones.”
Soon, non-inhibitor hemophilia patients may also benefit from emicizumab, says Genentech’s Dr. Levy, pointing to exciting clinical trial results for Hemlibra in people without factor VIII inhibitors. “Our HAVEN 3 study showed that Hemlibra prophylaxis resulted in a statistically significant and clinically meaningful reduction in treated bleeds compared to no prophylaxis. It also showed Hemlibra is the first medicine to significantly reduce bleeds compared to prior factor VIII prophylaxis, the current standard-of-care treatment for people without factor VIII inhibitors, as demonstrated by a statistically significant reduction in treated bleeds in an intrapatient comparison” (Mahlangu J, et al. N Engl J Med. 2018;379:811–822).
Based on the data from the HAVEN 3 trial, Genentech and Roche filed a supplemental biologics license application and were granted priority review for Hemlibra to treat adults and children with hemophilia A without factor VIII inhibitors. The FDA is expected to announce a decision on approval of this widened application in early October, Dr. Young says.
In the meantime, Genentech continues to address the issue of accurate test results by stressing education. “Education of patients and physicians is something that we take very seriously and will continue to do,” Dr. Levy says. “Separately, we are working to support the continued development of existing tests that may be of use to the hemophilia community, as well as new tests that may be of help to physicians in certain clinical scenarios.”
Anne Paxton is a writer and attorney in Seattle.