- Swiss pharma Roche's experimental hempohilia treatment emicizumab took a step closer toward winning U.S. approval, securing a Feb. 23 decision date from the Food and Drug Administration under the regulator's Priority Review program.
- Roche submitted emicizumab based on the results of the HAVEN 1 and HAVEN 2 pivotal studies, which tested the antibody drug in hemophilia A patients with inhibitors to standard factor VIII replacement therapies — a segment which makes up nearly a third of the total hemophilia A population.
- Emicizumab, pegged as a potential blockbuster, is one of the pharma giant's top clinical hopes. Its success could prove disruptive to Shire plc and Novo Nordisk S/A, both current leaders in the market for hemophilia drugs.
A pipeline of promising drugs, from emicizumab to gene therapies developed by BioMarin Pharmaceutical Inc. and Spark Therapeutics, Inc., could dramatically shake up the hemophilia market in coming years.
Roche's drug is the closest to market and an approval in February would offer a powerful new treatment option for patients who have developed resistance to standard replacement therapy.
In healthy people, proteins known as factor VIII help blood clot to prevent further bleeding. Hemophilia A patients, however, don't produce enough of these proteins, leading to uncontrolled bleeds. While factor VIII replacement therapy can help most patients, around a third develop antibodies known as inhibitors that bind and block replacement factor — putting those patients at higher risk.
In the HAVEN 1 study, prophylactic treatment with emicizumab reduced the number of treated bleeds by 87% compared to on-demand use of bypassing agents typically tapped to help clotting for inhibitor patients. Interim results from a second trial, HAVEN 2, showed only one of 19 children treated with emicizumab reported a treated bleed through three months.
Market enthusiasm for emicizumab, though, has been dampened somewhat by lingering safety concerns which emerged from the HAVEN 1 study.
Five patients experienced either thromboembolic (TE) events or thrombotic microangiopathy (TMA), and one patient died despite additional treatment with bypassing agents. Roche believes the side effects were tied to repeated, high doses of a bypassing agent but the events have still sparked concerns about the drug's safety.
No TE or TMA events have been observed in the HAVEN 2 study, and the drug still looks likely to be approved given the need for new treatment options for inhibitor patients. A third trial will test emicizumab in non-inhibitor patients and success there would broaden the number of patients Roche could reach.
Both Shire and Novo expect approval of emicizumab to cut into sales of their drugs currently used for inhibitor patients, yet have expressed confidence in the competitiveness of their respective hemophilia businesses.
"While we don't know for sure how much of our approximately $800 million in annual global sales of Feiba is at risk — and this will most certainly be impacted by the potential approval timing, the final label and the future clinical and real-world data generated from patient — we do think that the market's current expectation for up to 50% share erosion after five years post-launch is reasonable," explained Shire CEO Flemming Ornskov on an August 3 call with analysts.
Novo's chief financial officer Jesper Brandgaard has laid out a similar scenario for the Danish drugmaker's NovoSeven franchise, predicting about 50% of the drug's sales to be exposed to competition from emicizumab. Brandgaard expects any sales erosion to happen over time, predicting gradual uptake.