CTI Bites Off Big Chunk Of Myelofibrosis Market With Vonjo Approval
Executive Summary
The accelerated approval for the JAK2/IRAK1 inhibitor, CTI’s first commercial product, carves out an underserved market accounting for about one-third of the US myelofibrosis population.
The US Food and Drug Administration gave the drug accelerated approval on 28 February for patients with intermediate- or high-risk primary or secondary myelofibrosis with thrombocytopenia with a platelet count of less than 50 billion/liter. The drug is the first approved for cytopenic myelofibrosis.
Given that the label is for patients with less than 50 billion platelets/liter, chief commercial officer Jim Fong told a 1 March analyst call that the company’s marketing team would be promoting the drug for that particular population, despite the pivotal PERSIST-2 trial including those with up to 100 billion/liter and the safety data from that population being in labeling.
“Having said that, physicians, as you know, health care professionals, are allowed to use their best medical judgment in how they prescribe therapies, particularly in oncology,” he told the call. “And given the level of dissatisfaction and frustration we have heard through market research and advisory boards, we would not be surprised if there was spontaneous utilization of pacritinib in that population, particularly given the fact that [PERSIST-2] included that population.”
Fong told the call that while the severely thrombocytopenic patients included in Vonjo’s initial label represent about one-third of myelofibrosis patients, about another third have platelet counts up to 100,000/microliter. However, the confirmatory Phase III PACIFICA study is enrolling patients in the severely thrombocytopenic category, i.e. those with platelet counts below 50,000/microliter. Results are expected in mid-2025.
Lack Of Black Box A Potential Advantage
In PERSIST-2, patients were randomized to receive Vonjo at 200mg twice daily, 400mg twice daily or best available therapy, which included Incyte Corporation’s JAK2 inhibitor Jakafi (ruxolitinib), a longtime standard of care for myelofibrosis. Among the cohort of patients with platelet counts below 50 billion/liter treated with the 200mg dose of Vonjo, 29% experienced at least a 35% reduction in spleen volume, compared with 3% of those in the control arm.
The most common adverse events among patients receiving the 200mg dose – which the company is recommending – were diarrhea, thrombocytopenia, anemia, nausea and peripheral edema. Anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia and squamous cell carcinoma of the skin were the most frequent serious events among those receiving the drug at that dose, occurring in at least 3% of patients.
The company said that the population the drug is targeting represents about one-third of the approximately 21,000 people with myelofibrosis in the US and is a population poorly served by existing options, including Jakafi. On a call with analysts, CEO Adam Craig noted that Jakafi has been a mainstay of myelofibrosis care for years.
“However, despite its extensive use, the majority of treated patients are receiving low, sub-therapeutic doses of Jakafi, predominantly due to myelosuppression from the drug,” he said. That, he added, is despite Jakafi’s label recommending against giving the drug at 5mg twice daily due to its lack of efficacy.
Analysts also noted that unlike other JAK inhibitors, Vonjo’s label does not carry a black box warning.
“We believe the exclusion of a black box warning or any requirements for REMS protocols provide Vonjo with potential competitive advantages during brand promotion, particularly when comparing to low dose Jakafi which is currently being prescribed off-label,” Needham analyst Gil Blum said in a 1 March note.
He added that Bristol Myers Squibb Company’s JAK inhibitor Inrebic (fedratinib), which won approval in August 2019, does carry a black box warning. (Also see "Inrebic Approval Is A Boost For Myelofibrosis And Celgene's Buyer Bristol" - Scrip, 16 Aug, 2019.)
In another 1 March note, BTIG analyst Robert Hazlett pointed to Vonjo’s “differentiated” profile as a JAK2 inhibitor with specificity also for IRAK1, FLT3 and CSF1R, but without inhibiting JAK1 at clinically relevant concentrations. In addition to the significantly reduced spleen volume, he noted also that 23% of Vonjo-treated patients showed greater than 50% reductions in total symptom score (TSS), compared with 13% in the best-available-therapy group.
While not a direct competitor, another JAK inhibitor in development for myelofibrosis is Sierra Oncology, Inc.’s momelotinib, which the company is developing for patients with previous JAK inhibitor treatment, another setting with few therapy options. Results from a Phase III trial showed positive efficacy in that population, though a trial investigator cited patients with anemia as a “sweet spot.” (Also see "Sierra Sees Momelotinib ‘Sweet Spot’ In Anemic Myelofibrosis Population" - Scrip, 25 Jan, 2022.)
Priced For Unmet Need
Fong reported that Vonjo’s wholesale acquisition cost (WAC) will initially be $19,500 per month. The company anticipates that about 60% of prescriptions will come from the community setting, while the remaining 40% will be from academic medical centers.
“The price reflects Vonjo’s role as an important new therapeutic option serving a previously unmet medical need based on impressive data we have seen from the Phase III PERSIST-2 study,” Fong told the call.
BTIG’s Hazlett said Vonjo “has the potential to fill the material unmet need” among that group of patients not served by current JAK2-targeting drugs.
“Pacritinib has shown meaningful efficacy in these patients, and its novel profile that has a lack of myelosuppression is differentiated compared to currently available JAK2 therapeutics, and to those in development, which have limited consideration in thrombocytopenic [myelofibrosis] patients (those with platelet counts <100,000/mL) who represent approximately 2/3 of the ~20,000 US [myelofibrosis] population,” he said.
He said that in the low-platelet population, Vonjo’s annual sales could ultimately peak at more than $1bn. Needham’s Blum, meanwhile, projected sales of about $595m by 2026 in the US and EU.