While the excitement in hemophilia treatment has been all about the once-and-done approach of gene therapy, Roche (OTCQX:RHHBY) has in its own unspectacular way advanced an antibody now forecast to be one of only two blockbusters in the space in 2022.
The Swiss group is expected to report phase III data for emicizumab early next year in patients who have developed inhibitors to factor VIII clotting factors, putting it on track for approval in 2018. Gene therapies are moving swiftly, but if Roche can establish itself in hemophilia before them it has a good chance of meeting lofty expectations.
Saved by zero
Emicizumab, formerly known as ACE910, is a bispecific antibody binding to both factors IX and X, in so doing mimicking factor VIII, an essential coagulation factor that is suppressed in hemophilia patients because of genetic abnormalities. In contrast, the gene and RNAi therapies now in early and mid-stage trials have attempted to correct the condition by stimulating the body’s own factor VIII production.
Usual first-line treatment is with a recombinant factor VIII, and treatment protocols have been migrating from on-demand therapy after a bleeding episode to prophylactic treatment. Many patients develop antibodies that inhibit the effectiveness of these factor VIIIs. Roche’s phase III is testing emicizumab as a prophylactic in patients who have developed these inhibitors, but the company is believed to be preparing a trial in the broad hemophilia A population.
At the World Federation of Hemophilia meeting Roche released updated data from a phase I trial in 18 patients at three different dosing levels. The highest dose of 3mg/kg achieved a median annualized bleeding rate of 0 at 21.4 months of follow-up, consistent with the findings from this endpoint at 12 weeks.
Patients taking 1mg/kg had a median annualized bleeding rate of 0.2, and in those taking 0.3mg/kg it was 1.4, a reduction from 4.4 at the 12 week endpoint. Researchers saw effectiveness in all patients regardless of whether they have developed inhibitors.
A 2022 forecast of $1.5bn makes emicizumab Roche’s second-biggest clinical stage hope after the macular degeneration treatment lampalizumab. Analysts have doubled forecasts this year as positive news emerged and the phase III readout approached.
Bryan Garnier analyst Eric Le Berrigaud wrote this morning that emicizumab would face two commercial problems if it succeeds: achieving quick uptake when physicians may be reluctant to switch stable patients to emicizumab, and pricing emicizumab when payer costs for non-inhibitor patients are significantly lower than for those with inhibitors.
Final stop, payers
A third commercial issue is weekly subcutaneous injections, a vulnerability not unlike the frequent infusions of factor VIIIs like Advate. This is the selling point of the gene therapy approach, which hopes to change the course of the disease with a single episode of treatment.
In hemophilia A gene therapy BioMarin (NASDAQ:BMRN) presented proof-of-concept data from nine patients taking BMN 270. A single dose of BMN 270 stimulated factor VIII production equaling 50% or more of normal in six of the seven patients, a finding that sparked a 7% share rise yesterday.
RNAi therapy got a hearing in the form of Alnylam’s (NASDAQ:ALNY) fitusiran, a once-monthly injection that achieved an annualized bleeding rate of 0 in 17 evaluable patients with hemophilia A or B.
Gene therapy’s checkered history naturally has the sector skeptical as to its promise, while Roche’s record of success in the antibody space has perhaps resulted in a more bullish view for emicizumab – even if it requires more frequent dosing.
The hope of infrequent injections or perhaps a single treatment has its appeal, however, although it will be an expensive proposition. The last gatekeepers will be payers, who will be asked to accept that treatments potentially costing $1m or more will save money long-term. If emicizumab’s comparatively simple pricing conflict causes payers difficulty, just wait until gene therapy arrives.
Editor's Note: This article discusses one or more securities that do not trade on a major U.S. exchange. Please be aware of the risks associated with these stocks.