Pacritinib (Vonjo) received accelerated approval from the FDA at a twice daily, 200-mg dose for patients with intermediate- or high-risk primary or secondary myelofibrosis who are experiencing severe thrombocytopenia with a platelet count below 50 × 10

/L, according to a press release from CTI BioPharma Corporation.

The agency’s decision comes from results of the phase 3 PERSIST-2 study (NCT02055781).

Treatment with pacritinib at 200 mg resulted in a reduction in spleen volume of at least 35% for 29% of patients, vs 3% of patients who received the best available therapy, including ruxolitinib (Jakafi). As part of the post-approval plans for pacritinib, the phase 3 PACIFICA trial (NCT03165734) will be completed with results estimated in 2025.

“Today's approval of Vonjo establishes a new standard of care for myelofibrosis patients suffering from cytopenic myelofibrosis,” John Mascarenhas, MD, associate professor of medicine, hematology and medical oncology at Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, said in a press release. “Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 10

/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need. I am pleased to see that a new, efficacious and safe treatment option is now available for these patients.”

The PERSIST-2 study, which assessed the use of pacritinib compared with best available therapy in patients with myelofibrosis and thrombocytopenia, enrolled 311 patients. Those who enrolled were randomized into 1 of 3 treatment regimens, including pacritinib once daily (n = 104), pacritinib twice daily (n = 107), or a best alternative treatment (n = 100). Best alternative treatments included ruxolitinib (45%), hydroxyurea (19%), and prednisone and/or prednisolone (13%).

At the 24-week mark, 15% of patients taking pacritinib once daily and 22% taking the agent twice daily experienced a 35% or higher reduction in spleen volume compared with 3% of those taking a best alternative treatment. Differences between the 3 treatment groups did not reach significance in terms of overall survival, including between the once daily (HR, 1.18; 95% CI, 0.57-2.44) and twice daily pacritinib arms (HR, 0.68; 95% CI, 0.30-1.53). The treatment also yielded a 25% reduction in total symptom score of 50% or more in the pacritinib arms vs 14% in the control group.

Additionally, the phase 3 PERSIST-1 study (NCT01773187) examined the use of pacritinib vs best available therapy for myelofibrosis regardless of baseline cytopenias. Results from the trial indicated that pacritinib was well tolerated and resulted in sustained spleen volume and symptom reduction.

 This study showed that patients with baseline cytopenias could have a treatment option with pacritinib. At week 34, 19% (n = 42) of patients treated with pacritinib experienced a 35% or more reduction in spleen volume reduction compared with 5% (n = 5) in the best alternative treatment group (

The most common grade 3/4 adverse events through week 24 in the pacritinib group were anemia (17%), thrombocytopenia (12%), and diarrhea (5%) compared with anemia (15%), thrombocytopenia (11%), dyspnea (3%), and hypotension (3%) in the best available therapy cohort. A total of 12% (n = 27) of patients died in the pacritinib group and 13% (n = 14) in the best alternative treatment group died.

Pacritinib was also assessed as part of the dose-finding phase 2 PAC203 study (NCT03165734) vs ruxolitinib in patients with myelofibrosis and severe thrombocytopenia.

 Patients who were administered 200 mg of pacritinib twice daily experienced the highest reduction in spleen volume and total symptom score. In particular, patients with a baseline platelet count of less than 50 × 10

/L experienced a promising reduction in splenic volume (14%).

Patients who were treated with 200 mg of pacritinib twice a day did not experience an excess of grade 3 or higher hemorrhagic or cardiac events.

CTI BioPharma announces FDA accelerated approval of VONJO™ (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. News release. CTI BioPharma Corp. February 28, 2022. Accessed February 28, 2022. https://prn.to/3ppk5Cm

Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis. 

. 2018;4(5):652-659. doi:10.1001/jamaoncol.2017.5818

Mesa RA, Vannucchi AM, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. 

. 2017;4(5):e225-e236. doi:10.1016/S2352-3026(17)30027-3

Gerds AT, Savona MR, Scott BL, et al. Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. 

. 2020;4(22):5825-5835. doi:10.1182/bloodadvances.2020003314

Articles

Patients with intermediate- or high-risk primary or secondary myelofibrosis with a low platelet count may derive benefit from treatment with pacritinib following its accelerated approval by the FDA.  

Pacritinib Granted Accelerated Approval for Use in Myelofibrosis With Severe Thrombocytopenia 

In February 2022, the FDA granted accelerated approval to pacritinib for intermediate or high-risk primary or secondary myelofibrosis with severe thrombocytopenia.

Pacritinib for Myelofibrosis With Severe Thrombocytopenia

Ruben Mesa, MD, executive director of Mays Cancer Center, home of the UT Health San Antonio MD Anderson Cancer Center, spoke with CancerNetwork® about future research involving pacritinib (Vonjo) following its accelerated approval in intermediate- or high-risk primary or secondary myelofibrosis with severe thrombocytopenia. Mesa served as lead investigator on the PERSIST-1 trial (NCT01773187), which examined pacritinib in this setting.

We now have mature data in terms of what monotherapy with pacritinib looks like in the front-line or second-line setting, particularly for individuals with marked thrombocytopenia. Combination therapies are intriguing, and there are many interesting agents, almost 10 that have a different mechanism of action distinct from JAK2, that are in development. Many of them can cause thrombocytopenia themselves.

The approval of pacritinib is a significant advance for patients with myelofibrosis. It allows us to create a new group of individuals. Importantly, it also shows that this is a disease where multiple therapies are needed. There is a range of different phenotypes of the disease and many new mechanisms of action are being identified, even with IRAK-1 as an additional important new target. I’m excited to see this advance and excited to see our patients with myelofibrosis [given] more options.

Videos

Ruben Mesa, MD, spoke about why pacritinib in the treatment of myelofibrosis is beneficial. 

Mesa Considers Next Steps With Pacritinib in Myelofibrosis

Ruben Mesa, MD, executive director of Mays Cancer Center, home of the UT Health San Antonio MD Anderson Cancer Center, spoke with CancerNetwork® about which population of patients with myelofibrosis would benefit most from the accelerated approval of pacritinib (Vonjo).1 Mesa also spoke about the PERSIST-1 trial (NCT01773187), for which he is lead investigator.2 This trial aimed to determine if pacritinib vs best available therapy would improve outcomes in patients with myelofibrosis, regardless of baseline cytopenia.

The group of individuals with cytopenic myelofibrosis [will benefit the most from pacritinib] and that’ll be a natural part of the discussion, even patients who are JAK inhibitor naïve who have marked thrombocytopenia. There will be important use as second- or third-line therapy for individuals with myelofibrosis, particularly if they have cytopenic myelofibrosis.

If they have a platelet count under 50,000/μl, it will [offer the most unique option]. Any amount of thrombocytopenia under 100,000/μl, it will be a strong consideration both in the frontline and the second-line setting. There clearly is activity in the PERSIST-1 study [NCT01773187], where it was not limited only to patients with thrombocytopenia. It is active for individuals that have a normal platelet count. In those settings, it will be more in the second line alone or potentially in combinations.

1. CTI BioPharma announces FDA accelerated approval of VONJO™ (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. News release. CTI BioPharma Corp. February 28, 2022. Accessed February 28, 2022. 

2. Mesa RA, Vannucchi AM, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. 

Ruben Mesa, MD, spoke about which patients stand to benefit the most from the approval of pacritinib in myelofibrosis with severe thrombocytopenia. 

Mesa Talks Benefits of Pacritinib in Myelofibrosis With Marked Thrombocytopenia 

Ruben Mesa, MD, executive director of Mays Cancer Center, home to the UT Health San Antonio MD Anderson Cancer Center, spoke with CancerNetwork® about the accelerated approval of 

pacritinib (Vonjo) for intermediate or high-risk primary or secondary myelofibrosis with severe thrombocytopenia

. This approval adds to the toolkit of agents to combat JAK2 and other key targets.

Pacritinib is an important addition to the armamentarium we have for treating patients with myelofibrosis, in particular because of the safety and effectiveness that has been seen for a subset of patients with myelofibrosis that have low platelet counts. Myelofibrosis is a chronic leukemia, and it’s driven by genetic mutations such as JAK2,CALR, and MPL.Patients can have difficulties with splenomegaly, symptoms, cytopenias, or risk of progressing to acute leukemia.

Our current state of approvals of ruxolitinib [Jakafi] andfedratinib [Inrebic] have been for individuals with a platelet counts of 50,000/μl or above. Both of those agents can improve splenomegaly or symptoms but have an[adverse] effect of causing anemia or lowering the platelet count, with thrombocytopenia beinga dose-limiting toxicity.

Pacritinib, a JAK2 and IRAK-1 inhibitor, is somewhat distinct in that it can improve splenomegaly and symptoms to very important areas of burden in myelofibrosis. It has been safely used in individuals even with severe thrombocytopenia platelet counts of under 50,000/μl. It can be used, given as full dose, to improve splenomegaly and symptoms. Additionally, there has been improvement in an anemiain some individual’s or even turning from transfusion dependent to transfusion independent. It’s an important additional JAK inhibitor with a unique lanefor individuals with marked thrombocytopenia or the even the broader cytopenic myelofibrosis. I’m excited that to see this come.

CTI BioPharma announces FDA accelerated approval of VONJO (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. News release. CTI BioPharma Corp. February 28, 2022. Accessed February 28, 2022. https://prn.to/3ppk5Cm

Ruben Mesa, MD, spoke about the accelerated approval of pacritinib and its importance for the treatment of myelofibrosis with severe thrombocytopenia.  