EHA – At least Incyte can still count on Jakafi

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When you’re reeling from a pivotal trial disaster, and another potential blockbuster only just scraped through the US regulatory process, it is good to have one revenue driver you can count on. Step forward Incyte, whose Jakafi franchise is starting to look like one of the industry’s most reliable mainstays.

Findings presented today at the European Hematology Association congress suggest that Jakafi could have a positive effect on overall survival and thrombosis – claims that had earlier eluded it. And this is not the only trick that this Jak inhibitor might still have up its sleeve.

Additional uses could take it beyond its approved indications of myelofibrosis and polycythemia vera, though according to EvaluatePharma’s sellside consensus these still account for 96% of its nearly $4bn of forecast 2024 sales.

Waiting in the wings are such indications as graft-versus-host disease, a filing for which could come this year, and atopic dermatitis and vitiligo, the last two with a cream formulation coded INCB018424. The Asco meeting even saw data from a Jakafi trial in multiple myeloma.

Jakafi – a pipeline within a drug?
Global sales ($m)
Indication Status 2017 2024e Trial ID
Myelofibrosis Marketed 1,266 1,962 NCT00952289
Polycythaemia vera Marketed 644 1,854 NCT01243944
Graft-vs-host disease Phase III - 147 NCT03112603
Atopic dermatitis Phase II - - NCT03011892
Vitiligo Phase II - - NCT03099304
Multiple myeloma Phase I - - NCT03110822
Total 1,910 3,963
Source: EvaluatePharma sellside consensus.

Life has not been as kind to other Jak inhibitors. Incyte’s own Olumiant, a Jak inhibitor targeting rheumatoid arthritis and licensed to Lilly, was knocked back by a complete response letter; a refiling recently secured approval only for the lower of two doses because of thrombosis risk.

Thrombosis risk makes today’s EHA data with Jakafi look ironic. The findings relate to the pivotal Response trial in polycythemia vera subjects unresponsive to or intolerant of hydroxyurea, a study that failed to yield survival and thrombosis data owing to the large number of patients crossing over from control to active treatment.

To overcome this problem Novartis, Incyte’s Jakafi partner, carried out a comparison of the active cohort against a registry compiled by Gemfin, a Spanish group of healthcare professionals.

The results look stunning: Jakafi cut risk of death by 72%, and risk of thrombosis by 79%. As this is a cross-trial comparison the data should be treated with caution, though Novartis insists that the Gemfin registry comprises a similar patient cohort to that in Response.

Secondary lymphoma?

Interpretation of the analysis will now be up to prescribers of Jakafi and other Jak inhibitors. Though Incyte might not like it they will also need to bear in mind findings of a separate study, published yesterday in Blood, proposing a link between Jak inhibitor use in myelofibrosis and the development of B-cell lymphoma, an aggressive secondary malignancy.

This arose from an analysis of patients at the Medical University of Vienna, Austria, and found that 5.8% of 69 Jak inhibitor-treated subjects developed lymphomas, versus two of 557 patients who did not receive a Jak agent.

The main caveat is that the numbers are tiny, and the authors do not present a statistical analysis. However, they state that this type of 15-fold increase in lymphoma development was also seen in an independent cohort of myeloproliferative neoplasm patients.

They seem to have little doubt that Jak/Stat pathway activation is involved in elevated incidence of B-cell lymphomas. Interestingly, most of the lymphoma patients in the analysis had had a pre-existing B cell clone whose outgrowth was responsible for the subsequent malignancy.

Screening myelofibrosis patients for the gene rearrangements seen in this clone could avoid these subjects being prescribed Jak inhibitors, the authors suggest – a finding that should give Incyte comfort.

After the spectacular failure of its IDO inhibitor epacadostat the company can certainly do without further disappointments, and in Jakafi it does at least have a reliable blockbuster, whose $8.9bn NPV accounts for over half of Incyte’s market cap.

That said, when it comes to relying on one drug the company will surely be mindful of the lessons learned by Celgene and Seattle Genetics.

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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