FDA Approves Ojjaara (Momelotinib) for Treating High-Risk Myelofibrosis with Anemia a new competitor of Jakafi

GlaxoSmithKline, momelotinib, Ojjaara, FDA approval, myelofibrosis, MOMENTUM trial, SIMPLIFY-1 trial, intermediate or high-risk myelofibrosis

The FDA has granted approval for momelotinib, marketed as Ojjaara, as a groundbreaking treatment option for adult patients grappling with intermediate or high-risk myelofibrosis, encompassing both primary and secondary forms of the disease, in conjunction with anemia.

This milestone regulatory decision has been substantiated by compelling results emanating from the MOMENTUM trial (NCT04173494) in Phase 3, as well as data extracted from a subset of adult patients with anemia who were part of the Phase 3 SIMPLIFY-1 trial (NCT01969838).

MOMENTUM Trial Highlights

The primary endpoint of the trial focused on achieving a Myelofibrosis Symptom Assessment Form (MFSAF v4.0) TSS reduction of 50% or more at week 24 compared to baseline. Symptoms were meticulously tracked through patient diaries, which recorded disease-related symptoms such as fatigue, night sweats, itching, abdominal discomfort, pain under the ribs or left side, feelings of fullness after eating, and bone pain.

Additional endpoints encompassed transfusion independence (TI), spleen volume response (SVR), change in MFSAF v4.0 Total Symptom Score from baseline, and the percentage of patients requiring no transfusions.

The median age of patients was 71 years (ranging from 38 to 86), with a substantial portion (79%) aged 65 years or older. Over half of the patients were male (63%), and the majority identified as White (81%). Among the disease categories, 64% had primary myelofibrosis, 19% had post–polycythemia vera myelofibrosis, and 17% had post–essential thrombocytopenia myelofibrosis. As for risk stratification, 5% fell under intermediate-1 risk, 57% intermediate-2 risk, and 35% high-risk disease. In the eight weeks preceding study treatment, 79% of patients had received red blood cell (RBC) transfusions, with a median of 4 RBC units (interquartile range, 1-6).

“The vast majority of myelofibrosis patients eventually develop anaemia, causing them to discontinue treatments and require transfusions. Given this high unmet need, we are proud to add Ojjaara to our oncology portfolio and address a significant medical need in the community. We look forward to helping improve outcomes in this difficult-to-treat blood cancer.”

– Nina Mojas, Senior Vice President, Oncology Global Product Strategy, GSK

Furthermore, 13% of individuals in the momelotinib group were transfusion independent at baseline compared to 15% in the danazol group. Baseline metrics included a median hemoglobin count of 8 g/dL and a median platelet count of 96 × 109/L (ranging from 24 to 733). Palpable spleen length at baseline had a median of 11 cm below the left costal margin, with central spleen volume measured via MRI or CT at a median of 2105 cm3 (ranging from 609 to 9717).

Data analysis revealed that 25% of those in the momelotinib group experienced a MFSAF v4.0 TSS reduction of 50% or more, in stark contrast to the 9% of individuals in the danazol group, resulting in a significant treatment difference of 16% (95% CI, 6%-26%; P < .01). Moreover, 30% of momelotinib recipients achieved TI, as opposed to 20% of danazol recipients, indicating a noninferiority treatment difference of 14% (95% CI, 2%-25%; P = .023).

Additionally, 39% of those in the momelotinib group experienced an SVR of at least 25%, while only 6% in the danazol group achieved this milestone, representing a substantial difference of 33% (95% CI, 23%-44%; P < .0001). Furthermore, 22% of momelotinib patients achieved an SVR reduction of at least 35%, while this figure was only 3% in the danazol group, with a noteworthy difference of 18% (95% CI, 10%-27%; P = .001). The percentage of patients in the momelotinib group who required no transfusions during the 24-week treatment period stood at 35%, contrasting with 17% in the danazol group, marking a significant difference of 17% (95% CI, 8%-26%; P = .001). MFSAF v4.0 TSS change from baseline was markedly different, with momelotinib showing -9.4 compared to -3.1 for danazol, equating to a difference of -6.2 (95% CI, -10 to -2.4; P = .001).

Of those who received momelotinib, 72% were exposed to the agent for at least 24 weeks, and 52% continued treatment for at least 48 weeks.

Serious toxicities were encountered by 35% of patients, with 12% experiencing adverse effects (AEs) that proved fatal. Additionally, 34% of patients suffered AEs necessitating dose reduction or interruption, while 18% experienced AEs leading to treatment discontinuation.

SIMPLIFY-1 Study Overview

The primary efficacy endpoint focused on achieving a reduction in SVR by 35% or more. Results demonstrated that 31.4% (95% CI, 21.8%-42.3%) of patients in the momelotinib arm (n = 86) achieved this target, as opposed to 32.6% (95% CI, 23.4%-43.0%) of patients in the danazol arm (n = 95).

Serious AEs were observed in 28% of patients, with one fatal AE documented. Furthermore, 21% of patients necessitated dose interruptions or reductions due to toxicities, and 19% experienced AEs leading to treatment discontinuation.

“We are thrilled to see momelotinib reach the clinic, giving patients and their physicians another option to help manage myelofibrosis. Any new treatment that takes steps toward unlocking the mysteries of this complex and chronic blood cancer represents great progress for the field.”

– Kapila Viges, Chief Executive Officer, MPN (Myeloproliferative Neoplasms) Research Foundation

This FDA approval for momelotinib brings a ray of hope to the myelofibrosis patient community, particularly those grappling with anemia, offering an effective treatment option with promising outcomes.

GSK’s Ongoing Endeavors and Incyte’s Setbacks

GSK initially acquired Ojjaara as a complement to its blood cancer drug, Blenrep, which targets BCMA. However, GSK made the decision last year to withdraw Blenrep’s accelerated approval for late-line multiple myeloma due to its failure in a confirmatory trial. Furthermore, the European Medicines Agency’s human medicines committee has recently declined to renew Blenrep’s conditional authorization, indicating a potential withdrawal from the EU market once the negative opinion is officially adopted by the European Commission.

Despite these setbacks, GSK is still actively involved in two phase 3 trials exploring Blenrep combinations for second-line treatment, and we can anticipate updates on these trials later this year.

Incyte is also in the process of pairing Jakafi with other therapeutic agents. However, this Delaware-based pharmaceutical company encountered an obstacle when the FDA rejected an extended-release formulation, disrupting its plans to introduce fixed-dose combinations.

In GSK’s expanding oncology portfolio, Jemperli achieved a significant milestone in July by securing the first FDA approval in the PD-1/L1 class for use as a frontline treatment for endometrial cancer characterized by either a deficiency in mismatch repair (dMMR) or high microsatellite instability (MSI-H).

These developments in the pharmaceutical landscape reflect the dynamic nature of cancer treatment and the ongoing efforts to advance therapies and improve patient outcomes.

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