Polycythemia Vera: Growing Competition and the Changing Treatment Landscape in 2025

JAKAFI’s demand continues to grow in Polycythemia Vera

The therapeutic paradigm for Polycythemia Vera patients has shifted significantly in the last few years. Previously, the Polycythemia Vera treatment landscape was dominated by generic medicines such as aspirin, hydroxyurea, interferons, and phlebotomy until the approval of JAKAFI (ruxolitinib) in the US in 2014, a JAK inhibitor developed by Incyte as a second-line treatment for Polycythemia Vera patients. Another achievement in this space emerged in 2021 when PharmaEssentia’s BESREMi, an interferon, was approved in the United States as a monotherapy in the first-line setting. This content is a walkthrough of the most potential competitors in the Polycythemia Vera market. Emerging drugs to treat polycythemia vera offer innovative solutions, improving symptom management and enhancing patients’ quality of life. JAK inhibitors revolutionize polycythemia vera treatment with targeted therapy.

Incyte has already entrenched approval of JAKAFI as a second-line therapy in Polycythemia Vera. In addition to Polycythemia Vera, the drug has been approved for multiple indications, including myelofibrosis (MF), the first indication in JAKAFI’s label, and more recently in acute and chronic GvHD. Incyte has been successful in proving its market dominance by exploring multiple indications. In terms of Polycythemia Vera, the drug is also approved in the EU and Japan by the name of JAKAVI, with Novartis as a commercial partner outside the US. A supplemental New Drug Application (sNDA) for ruxolitinib cream in pediatric atopic dermatitis has been submitted, with potential approval anticipated in the second half of 2025.

Incyte has reported a net revenue of USD 741 million in Q3 2024 (+16% Y/Y); raising full year 2024 JAKAFI guidance to a new range of USD 2,740 – USD 2,770 million. Net product revenues were primarily driven by patient demand, which increased 10% in the third quarter of 2024 versus the same quarter in the prior year, with growth across all indications. The company has reported that approximately 35% of the prescriptions of JAKAFI were in Polycythemia Vera in Q3 2024. This attributes to JAKAFI’s well-established therapeutic efficacy and traction in patients as a second-line therapy. Given its well-established therapeutic efficacy and traction in patients as a second-line Polycythemia Vera therapy, we believe that the drug will attain its peak in Polycythemia Vera due to the impact of emerging therapies in the US by 2026, with a revenue of approximately USD 1.3 billion. Moreover, a further decline in its revenue is expected by approximately >50% in 3-4 years following its patent expiry in 2028 and the entry of rusfertide in the US market.

JAKAFI’s generics: Possible delay in entry?

The patent expiration in mid-2028 might be the most significant obstacle to JAKAFI’s supremacy in the Polycythemia Vera market. To address this, Incyte introduced the LIMBER (Leadership in MPNs and GVHD BEyond Ruxolitinib) life-cycle management initiative, which was meant to explore different monotherapy and combination methods to enhance and expand therapies for patients with MPNs and GVHD. The initiative is currently focusing on developing a novel once-daily ruxolitinib formulation; ruxolitinib-based combinations with new targets such as PI3K, BET, and ALK2; and new treatment alternatives such as mutant CALR. If this LIMBER initiative receives a green signal, the company may be able to prolong its patent, delaying the arrival of generics into the market.
In the long term, it will be fascinating to observe how JAKAFI is prescribed after BESREMi enters the Polycythemia Vera treatment market, or maybe rusfertide, which might be a contender if approved.

PharmaEssentia’s new entrant, entry into NCCN guidelines, insights on pricing, and launches

Besremi is a breakthrough treatment for polycythemia vera, offering improved disease control, reduced symptoms, and better long-term management outcomes. PharmaEssentia’s BESREMi (ropeginterferon alfa-2b), a monopegylated proline interferon is a new entrant for first and more advanced-line Polycythemia Vera patients without symptomatic splenomegaly; it is one of the first to be approved for the condition. BESREMi approval was stated in Q4 2021 in the US; therefore, meaningful sales began from 2022. Before the launch in the US, the drug was approved in the EU since 2019 and has been available in Germany, France, and the UK since 2020, whereas in April 2022, the drug was approved for reimbursement by Italy’s National Health Service (SSN). BESREMi was approved in Japan in 2023. In 2024, Besremi received approvals in countries such as Canada and Malaysia, and until now it has been approved in approximately 40 countries globally. Besremi side effects may include flu-like symptoms, injection site reactions, fatigue, headache, nausea, anemia, and liver function abnormalities.

BESREMi is a subcutaneous pen self-administered once every 2 weeks or monthly during long-term maintenance. BESREMi gained US approval in 2021 with an annual price more than USD 180,000, whereas in certain EU countries, annual pricing range from USD 60,000–110,000.

As the first approved medicine in the first line, it is expected to be the primary promotional voice in this market. Though interferon alfa-2b-based medications have been used to treat Polycythemia Vera for a long time, BESREMi differs from its predecessors due to its effectiveness, infrequent dose, and safety profile. More significantly, BESREMi’s long-term efficacy data over current SOC based on 7.5 years of evaluation is impressive and could provide strong support for the drug’s long-term treatment benefit over competing treatments. Because BESREMi’s label is broad (first and subsequent lines of therapy), PharmaEssentia has more leeway in positioning BESREMi in diverse therapeutic situations. Given BESREMi’s position upstream of JAKAFI in the NCCN recommendations, the drug is not a direct competitor for JAKAFI, but it has the potential to hinder progression of patients to JAKAFI usage, which might affect JAKAFI’s overall revenue.

We expect BESREMi’s peak in the US by 2027 until other late-stage assets, such as rusfertide, establish themselves in the market. Based on our analysis, BESREMi could potentially have at least 5 years, if not more lead time, in the market before other entrants, such as rusfertide, create stability for themselves. Moreover, the patent for BESREMi is expected to expire in 2034, allowing generics to enter the Polycythemia Vera market and hinting at a rapid decline in revenue. The dynamics of the BESREMi market are anticipated to change in the coming years owing to increased usage of BESREMi as a first line treatment for Polycythemia Vera, launch of a pen device version for Polycythemia Vera, expected launches in other potential indications, and global launch in various geographies.

Protagonist therapeutics’ Rusfertide a potential therapy for Polycythemia Vera patients

Rusfertide has a unique approach to treating Polycythemia Vera, it is an injectable treatment which can be self-administered by patients, reducing frequency of hospital visits and it is able to restrict the overproduction of red blood cells by mimicking the activities of the Hepcidin hormone. Takeda is Protagonist’s Co-development, the US Co-commercialization partner with 50:50 profit share, and with exclusive Ex-US rights is responsible for leading global commercialization activities. Final data from the rusfertide Phase II REVIVE study showed that rusfertide, when added to therapeutic phlebotomy with or without cytoreductive therapy achieved long term durable control of hematocrit below the 45% threshold for over 3 years. Polycythemia vera medications manage symptoms and control blood production. The Phase III VERIFY study is currently underway to assess rusfertide in Polycythemia Vera, with topline results expected in the first quarter of 2025. The company expects NDA submission in the fourth quarter of 2025, followed by potential approval in the fourth quarter of 2026, and commercial launch targeted for 2027. Rusfertide side effects may include injection site reactions, fatigue, headache, nausea, dizziness, and potential changes in blood iron levels.

Given its very different MoA compared to JAKAFI and BESREMi, rusfertide could become a viable alternative as an earlier line of therapy. Rusfertide might have the edge over current treatment, considering that JAK inhibitors have side effects that can be fatal, and the data available till date shows that rusfertide has the ability to become the new standard of care as the drug substantially reduces the frequency of phlebotomy, which affects the quality of life.

Earlier withdrawl of Breakthrough Therapy Designation (BTD)

Before the results were published, the US FDA slapped a full clinical hold in 2H 2021 after an animal study showed that mice developed benign and malignant skin tumors using the drug. Still, the hold was lifted soon after the company handed over individual patient clinical safety reports. This did not stop here; in 1Q 2022, the company received a letter from the FDA indicating the FDA’s intent to rescind Breakthrough Therapy Designation (BTD) for rusfertide in Polycythemia Vera, following which the company voluntarily withdrew its BTD following correspondence with the FDA and based on the internal analysis of the relative utility of BTD for

In a nutshell, Polycythemia Vera Market over the next few years is expected to substantially change and experience growth, as it will be dominated by two already approved products, JAKAFI and BESREMi. In contrast, we also anticipate the launch of a third product, rusfertide, in the US market in the coming 2–3 years. Considering that the symptomatic cases of Polycythemia Vera are the ones that get diagnosed, around a moderate range of 60–70%, we expect the market to expand, especially as safer and more effective therapies enter the market. Other competitors apart from Protagonist Therapeutics in the Polycythemia Vera space include Italfarmaco, Ionis Pharmaceuticals, Merck, Silence Therapeutics, and others.