The future of haemophilia could lie with neither factor inhibitors nor gene therapy, but instead with antibodies. In its currently approved population of haemophilia A patients with factor inhibitors, Roche’s Hemlibra has been judged to be more cost-effective than alternative therapies, which should help erase payers’ doubts about its annual price tag exceeding half a million dollars.
Hemlibra’s clear dominance of this treatment-resistant population might reveal Roche’s true aim: a product priced at parity or below for the larger population of haemophilia patients who have not developed inhibitors. This canny strategy could prove to be a blow to Shire and embarrass the business development division of Sanofi, which last week spent $11.6bn on the haemophilia specialist Bioverativ.
Icer released a draft assessment of haemophilia treatments, finding that, over the lifetime of a haemophilia patient who develops inhibitors at age 12 or older, Hemlibra costs the healthcare system $71m less than prophylaxis with the bypassing agents used when factor VIII inhibitors fail. Those agents include Shire’s Feiba and Novo Nordisk’s Novoseven.
Hemlibra’s advantage comes from a lower lifetime price – $15m versus $81m – in this scenario, and fewer lifetime bleeding events – 107 to 221.
It is uncommon for an innovative drug to come in as both more effective clinically and lower priced, but it speaks to Roche’s intention to take on the entire haemophilia A market.
Roche’s pricing strategy is a clue that it never saw bypassing agents as the main competitors to Hemlibra. Rather than the $4m annual price of bypassing agents dosed prophylactically for adults, the company chose a price point of about $700,000, according to Icer’s analysis. This should compare favourably to the cost of factor VIII replacement therapies like Bioverativ’s Eloctate and Shire’s Advate, which come in at $469,000 and $219,000 per patient per year respectively, according to EvaluatePharma data.
The non-inhibitor market is much bigger, with three in four patients remaining inhibitor-free. Roche has said that its pivotal trial in the non-inhibitor population, Haven 3, met its primary endpoint, although statistical analysis is being held back for a medical meeting. Once those data are available payers and organisations like Icer will be able to assess how Hemlibra shapes up against the factor VIII therapies in patients without inhibitors.
Just like Haven
Haven 3, detailed data from which could be revealed in May, was a trial of Hemlibra against no prophylaxis to determine how well Roche's agent reduces bleeding events (Roche’s latest Hemlibra win leaves no safe Haven for Shire, November 20, 2018). To equal Advate, it would need to show an annualised bleeding rate of 5-5.2 in children and adolescents and 1 in adults; to beat Eloctate, it would need to hit 1.6 in patients age 12 or older and 2 in patients younger than 12.
Among the inhibitor patients in Haven 1, Hemlibra achieved an annualised bleeding rate of 5.5, compared with 28.3 in subjects who received no prophylaxis.
Should Hemlibra merely match the factor therapies it has dosing on its side, as a once-weekly subcutaneous injection rather than an intravenous infusion multiple times a week.
And if Hemlibra beats the two on reducing bleeding episodes, the strategies of Shire and Sanofi could be disrupted. Shire’s two factor VIIIs, Advate and the longer-acting Adynovate, are forecast to constitute about $2bn of that group’s $17.8bn sales in 2022 – which could make its $32bn takeout of Baxalta look a little pricey.
The same is true for Sanofi, which placed an $11.6bn bet on the durability of factor-replacement therapies when it bought Biogen's spinout Bioverativ.
As for gene therapy and DNA/RNAi therapeutics, which could prove to be equally disruptive, Hemlibra’s price could yet make for a ripe target – if these next-generation projects work. Biomarin’s valoctocogene roxaparvovec wowed haematologists at the Ash meeting in December, and a plausible $1m price tag for a once-and-done treatment in haemopilia could look like a bargain next to Hemlibra, which still had a lifetime cost of $19.2m in the inhibitor population.
This would, of course, require patients to be willing to take a chance on gene therapy, which is still a young treatment technique compared with antibodies. In any case, Roche appears ready with a strategy to lower Hemlibra’s cost, with dosing every four weeks.
Hemlibra is emerging as the standard to beat in haemophilia A. Now that the Roche agent has been judged to chop millions off the lifetime costs of treating patients with inhibitors, rivals like Shire and Sanofi need to consider how they can adjust their pricing strategies to meet this new threat.