Roche’s Hemlibra: Market expansion approved, but safety an initial concern?

The annual industry forecast and analysis report Drugs to Watch from Clarivate Analytics was published in March 2018, detailing the pharma industry’s expected blockbuster launches for 2018. The report was led by Roche/Chugai’s hemophilia drug Hemlibra (emicizumab), for which analysts had very big expectations, and consensus forecasts stood at $4.002 billion for 2022 at the time of report publication.

This forecast assumed expansion of the drug’s label beyond its initially approved indication, which took place as expected in October 2018 with approval in patients without Factor VIII inhibitors.¹

Clarivate’s 2018 Drugs to Watch report was led by Roche/Chugai’s hemophilia drug Hemlibra (emicizumab), for which analysts had very big expectations.”

Hemlibra is a bispecific antibody which binds to Factor X and Factor XI, thus restoring the function of Factor VIII which is necessary for hemostasis. The drug was initially approved in the U.S. in November 2017 for patients with hemophilia A who have developed inhibitors²; up to 30% of patients develop these inhibitors as a consequence of Factor VIII treatment, a serious and challenging complication of treatment since bleeds no longer respond to standard therapy.³ Approvals for hemophilia A with inhibitors in both the EU⁴ and Japan⁵ followed in February 2018 and March 2018, respectively.

While sales in this setting will be robust given the unmet medical need, longer-term sales growth is expected to come from the broader hemophilia A market in patients without inhibitors, where the drug will compete with current standard of care Factor VIII replacements. Roche completed the HAVEN 3 study in patients without inhibitors, which reported data in November 2017 demonstrating superiority to prior Factor VIII prophylaxis in reducing treated bleeds in intra-patient comparison; the median annualized bleed rate was zero with Hemlibra dosed once or twice a week versus 40.4 for patients not receiving prophylaxis.⁶ The FDA granted Breakthrough designation in this setting in April 2018⁷, which expedited approval.

However, despite approval in this new setting, prescribers are likely to remain concerned about safety, as there are still some unknowns on the drug’s mechanism of action and the drug has a boxed warning on the potential for thromboembolism. This was confounded by reports at the end of March 2018 of five deaths among patients treated with the drug⁸, which could reignite concerns. Although no causal link to drug treatment was confirmed, prescribers may be hesitant to use the drug in patients without inhibitors, where there is less unmet need, until longer-term data are available – which could temper sales.

However, despite approval in this new setting, prescribers are likely to remain concerned about safety, as there are still some unknowns on the drug’s mechanism of action…”

It appears that these potential cautions have had more of an impact than expedited approval in the non-inhibitor setting, and Cortellis Consensus Forecast data (source Thomson Reuters I/B/E/S) have dropped significantly from when Drugs to Watch was published seven months ago, now standing at $2.667 billion for 2022. While lower than previously forecast, these sales are more than the peak sales of any previous FVIII replacement therapy, with previous market leader Advate reaching peak sales of $2.3 billion. Furthermore, as physicians become more familiar with key aspects of the drug’s efficacy and gain more safety experience, there could be an inflection point in sales as physicians increasingly start to recommend use in non-inhibitor patients and uptake ramps up.

Read the 2018 Drugs to Watch report

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