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New Data Could Make Roche Drug a Hemophilia Standard, But for How Long?

Xconomy San Francisco — 

It’s been a bumpy ride for emicizumab (Hemlibra) in 2018. The Roche/Genentech drug, approved by the FDA in late 2017, has a chance to become the choice treatment for people with hemophilia A, and new data today help that case. But will safety concerns and emerging competition blunt its rise?

At the World Federation of Hemophilia’s World Congress in Scotland today, Roche’s South San Francisco-based Genentech unit disclosed details from two Phase 3 studies of emicizumab, an antibody drug for hemophilia given via a subcutaneous injection. Genentech reports that both studies are positive.

The trials, called HAVEN-3 and HAVEN-4, are meant to expand the reach of emicizumab, currently approved for the roughly 20 percent of hemophilia A patients with “inhibitors,” or immune responses that require the use of additional expensive drugs. Hemophilia, which affects an estimated 400,000 worldwide, is typically treated prophylactically with infusible drugs given multiple times a week that boost levels of the clotting proteins, or factors, these patients lack. Emicizumab is given once a week via subcutaneous injection, but Genentech is trying to prove it can be taken by more hemophilia A patients, and less frequently, than other drugs. The firm will submit the new data to regulators in the U.S. and Europe for approval.

HAVEN-3 tested emicizumab in 152 hemophilia A patients without inhibitors. Emicizumab succeeded in the main goal of the study; a low and high dose of the drug reduced bleeds, per year, by 96 and 97 percent, respectively, compared to placebo. Genentech said 55.6 percent of people on a low dose and 60.0 percent of those on a high dose didn’t have any bleeds after a year of treatment.

Important to note: Genentech also reported that patients who switched from other preventative therapies to weekly injections of emicizumab saw their bleeding rates cut by 68 percent, from an estimated 4.8 per year to 1.5 per year. That’s the first time a hemophilia medicine has beat prophylaxis head to head in a clinical trial, said study investigator Johnny Mahlangu, of the University of the Witwatersrand and NHLS (South Africa), in a statement. And it’s an important finding as Genentech aims to show emicizumab can supplant other hemophilia A drugs, among them Shire’s FEIBA, which hemophilia A patients with inhibitors often have to take on top of other treatments to prevent bleeds.

Emicizumab also passed the 48-patient HAVEN-4, a single-arm study that tested the drug once a month in hemophilia A patients with or without inhibitors. Genentech said patients on a monthly dose had a median of zero bleeds requiring treatment per year; 56.2 percent of patients had none, and 90.2 percent of patients had three or less.

Genentech didn’t report any surprising or serious safety concerns. The most common side effects were injection site reactions, joint pain, cold, headache, upper respiratory tract infections, and flu. That’s positive news because safety problems have been a thorny issue for emicizumab. The FDA gave the drug a black box warning for severe blood clots, and in April, the nonprofit Hemophilia Federation of America reported in a letter that a total of five patients on emicizumab had died. (Genentech said none of the cases were related to its drug).

Taken together, the new emicizumab data are a “major step forward” for hemophilia A patients with inhibitors, wrote Jefferies analyst Ian Hilliker. Emicizumab could now become the new standard of care for all hemophilia A patients and generate up to $5 billion a year at its peak, he wrote in a research note.

The economics of treatment help its cause. Last year, for instance, Hemophilia Federation of America president Kimberly Haugstad told Xconomy that the cost to a severe adult patient who receives regular treatment several times a week and doesn’t suffer any bleeding episodes is “quite easily” $250,000 to $400,000 worth of factor each year. The bills run higher for those who have inhibitors, possibly north of $1 million per year. That’s partly why the nonprofit drug pricing hawk ICER (The Institute for Clinical and Economic Review) concluded, in a research report, that emicizumab presently “improves health while lowering costs.” The drug launched with a $482,000 list price for the first year and $448,000 each year afterwards, a discount to Feiba. It generated $23 million in its first quarter on the market.

But big change is on the way in hemophilia, and soon—which could give payers more levers to pull. Haugstad, for example, told Xconomy last year that patients are concerned that payers may start implementing restrictive formularies. And more drugs are coming.

An RNA interference treatment from Alnylam Pharmaceuticals (NASDSAQ: ALNY), fitusiran, for both hemophilia A and B patients—subcutaneous, taken monthly, and cheaper to produce than biologic drugs—is in late-stage testing. It could directly compete with emicizumab. Gene therapy, which offers at least the potential for a one-time, long-lasting treatment, is advancing too. A BioMarin Pharmaceutical (NASDAQ: BMRN) gene therapy for hemophilia A is in late-stage testing, with results expected next year. Leerink Partners analysts recently speculated that hemophilia gene therapy, if it works, could cost $1.5 million in the U.S., citing the known, long-term costs of standard treatment and how eliminating them could save money. (As Xconomy reported last year, this argument is complicated and has several important nuances.) One caveat to the ICER report, for instance, was that its positive conclusion about emicizumab was based on a comparison to the “huge costs currently associated with treating hemophilia.”

“High drug prices, paired with an insurance structure that often requires significant patient cost sharing, results in overwhelming financial burdens for families year after year—so extreme that even a cost-saving treatment like emicizumab likely won’t prevent these families from reaching their out-of-pocket maximum payment,” said ICER chief medical officer David Rind, in a statement earlier this year. “Payers, manufacturers, and policy makers must seek new approaches to address financial toxicity across the hemophilia landscape.”

Another issue to keep an eye on: Genentech said in late April that a patient in one of its studies, Haven 2, developed an antibody that neutralized the drug. To be clear, that’s the only confirmed case so far, but it’s worth watching, as is the progress of gene therapy. Here’s more on that, emicizumab, and the fast-moving hemophilia treatment landscape.