CTI BioPharma Corp CTIC

SEATTLE, Dec. 11, 2022 /PRNewswire/ -- CTI BioPharma Corp. (Nasdaq: CTIC) today announced an oral presentation and two poster presentations from the Company's pacritinib program at the 64^th American Society of Hematology (ASH^®) Annual Meeting and Exposition, taking place in New Orleans, Louisiana and virtually December 10-13, 2022.

A new post-hoc data analysis from the Phase 3 PERSIST-2 trial of pacritinib, a novel JAK2/IRAK1 inhibitor approved by the U.S. Food and Drug Administration (FDA) for patients with myelofibrosis and severe thrombocytopenia (platelet count below 50 x 10⁹/L), highlights pacritinib's potential anemia benefit in patients with myelofibrosis through its inhibition of Activin A receptor type 1 (ACVR1).

"The ACVR1/hepcidin pathway has a major role in the control of anemia in patients with myelofibrosis. Importantly, pacritinib has now been shown to be a potent ACVR1 inhibitor that reduces hepcidin levels in vitro. Furthermore, in the PERSIST-2 trial, at the approved dose of 200 mg twice daily (BID), treatment with pacritinib led to transfusion independence in patients with myelofibrosis who required red blood cell (RBC) transfusions," said Dr. Stephen Oh, MD, PhD, Associate Professor of Medicine, Hematology Division at Washington University School of Medicine in St. Louis. "As anemia poses a substantial burden for patients with myelofibrosis, the potential role of pacritinib in addressing anemia is highly encouraging."

"As our understanding of the mechanism of action of pacritinib expands, the full potential of pacritinib as a therapy for cytopenic myelofibrosis is emerging," said Adam Craig, MD, PhD, President and Chief Executive Officer of CTI BioPharma. "We continue in our commitment to meaningfully change the treatment paradigm for cytopenic myelofibrosis."

Presentation materials will be available at ctibiopharma.com.

The details of the oral presentation are as follows:

Pacritinib Is a Potent ACVR1 Inhibitor with Significant Anemia Benefit in Patients with Myelofibrosis

Abstract Number: 628
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Towards Personalized Medicine in Myeloproliferative Neoplasms and Mastocytosis: New and Repurposed Drugs for Unmet Clinical Needs
Session Date: Sunday, December 11, 2022
Presentation Time: 5:15–5:30 p.m. CST/6:15–6:30 p.m. EST
Presenter: Dr. Stephen Oh

Pacritinib is a novel JAK2/IRAK1 inhibitor approved by the U.S. FDA for patients with myelofibrosis and severe thrombocytopenia (platelet count <50 x 10⁹/L) and can be administered at the full approved dose (200 mg BID) regardless of cytopenias. Pacritinib demonstrated hemoglobin improvement in the randomized Phase 3 PERSIST-2 study, though the mechanism behind and the extent of pacritinib's anemia benefit has not been fully described. A retrospective analysis of the Phase 3 PERSIST-2 study was performed to assess pacritinib's in vitro potency against ACVR1 and its ability to reduce hepcidin and to describe the impact of pacritinib 200 mg BID on RBC transfusion independence.

Results from in vitro testing suggest pacritinib is a potent ACVR1 inhibitor that reduces hepcidin expression. Analysis of the clinical data shows that pacritinib therapy results in transfusion independence in patients with myelofibrosis who require RBC transfusions. Given this unique mechanism of action, pacritinib may provide a therapeutic option that provides spleen, symptom and anemia benefits to patients with myelofibrosis.

The details of the poster presentations are as follows:

Differential Impact of Thrombocytopenia and Anemia on Myelofibrosis (MF) Symptom Burden

Abstract Number: 1712
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Session Date: Saturday, December 10, 2022
Presentation Time: 5:30–7:30 p.m. CST/6:30–8:30 p.m. EST
Presenter: Dr. Jeanne Palmer

Patients with myelofibrosis and thrombocytopenia (platelet count <50 x 10⁹/L) report worse fatigue, inactivity, early satiety and quality of life compared to patients with higher platelet counts. Because thrombocytopenia and anemia frequently co-occur in myelofibrosis, the relative impact of thrombocytopenia and anemia on myelofibrosis symptoms is unknown. A retrospective analysis of baseline data from the Phase 3 PERSIST-1 and Phase 2 PAC203 trials was performed to describe the differential impact of thrombocytopenia and anemia on symptom burden by analyzing symptom data from patients with myelofibrosis who have isolated thrombocytopenia (platelet count <100 x 10⁹/L and hemoglobin ≥8 g/dL) versus isolated anemia (platelet count ≥100 x 10⁹/L and hemoglobin <8 g/dL).

Results showed that patients with isolated thrombocytopenia had more severe symptom burden than those with isolated anemia, particularly with physical function- and spleen-related symptoms. While amelioration of anemia is an important therapeutic goal for patients with cytopenic myelofibrosis, these data suggest that additional efforts aimed at the control of platelet count and underlying disease should be implemented to achieve optimal symptom control.

PACIFICA: A Randomized, Controlled Phase 3 Study of Pacritinib Versus Physician's Choice in Patients with Primary or Secondary Myelofibrosis and Severe Thrombocytopenia

Abstract Number: 4316
Session Name: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Poster III
Session Date: Monday, December 12, 2022
Presentation Time: 6:00–8:00 p.m. CST/7:00–9:00 p.m. EST
Presenter: Dr. John Mascarenhas

Pacritinib is a novel JAK2/IRAK1/ACVR1 inhibitor approved by the U.S. FDA for patients with myelofibrosis and severe thrombocytopenia (platelet count <50 x 10⁹/L). So far, treatment options for patients with myelofibrosis and severe thrombocytopenia are limited due to the high incidence of treatment-related thrombocytopenia when other JAK inhibitors are used. Previously, pacritinib demonstrated clinical activity in myelofibrosis in two Phase 3 studies (PERSIST-1 and PERSIST-2) and a Phase 2 dose-finding study (PAC203), all of which included patients with severe thrombocytopenia. PACIFICA is a multinational, multicenter, 2:1 randomized, controlled Phase 3 trial (NCT03165734) designed to confirm the efficacy and safety of pacritinib 200 mg twice daily vs physician's choice therapy in patients with myelofibrosis and severe thrombocytopenia.

About VONJO^® (pacritinib)
Pacritinib is an oral kinase inhibitor with activity against wild type Janus Associated Kinase 2 (JAK2), mutant JAK2^V617F form, IRAK1, ACVR1 (ALK2) and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Myelofibrosis is often associated with dysregulated JAK2 signaling. At clinically relevant concentrations, pacritinib does not inhibit JAK1.

VONJO is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 x 10⁹/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). CTI is conducting the Phase 3 PACIFICA study of VONJO in patients with myelofibrosis and severe thrombocytopenia as a post-marketing requirement.

Important VONJO Safety Information
Hemorrhage:
Serious (11%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <100 x 10⁹/L. Serious (13%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <50 x 10⁹/L. Grade ≥3 bleeding events (defined as requiring transfusion or invasive intervention) occurred in 15% of patients treated with VONJO compared to 7% of patients treated on the control arm. Due to hemorrhage, VONJO dose reductions, dose interruptions, or permanent discontinuations occurred in 3%, 3%, and 5% of patients, respectively.

Avoid use of VONJO in patients with active bleeding and hold VONJO seven days prior to any planned surgical or invasive procedures. Assess platelet counts periodically, as clinically indicated. Manage hemorrhage using treatment interruption and medical intervention.

Diarrhea:
VONJO causes diarrhea in approximately 48% of patients compared to 15% of patients treated on the control arm. The median time to resolution in VONJO-treated patients was two weeks. The incidence of reported diarrhea decreased over time, with 41% of patients reporting diarrhea in the first eight weeks of treatment, 15% in weeks 8 through 16, and 8% in weeks 16 through 24. Diarrhea resulted in treatment interruption in 3% of VONJO-treated patients. None of the VONJO-treated patients reported diarrhea that resulted in treatment discontinuation. Serious diarrhea adverse reactions occurred in 2% of patients treated with VONJO compared to no such adverse reactions in patients in the control arm.

Control pre-existing diarrhea before starting VONJO treatment. Manage diarrhea with antidiarrheal medications, fluid replacement, and dose modification. Treat diarrhea with antidiarrheal medications promptly at the first onset of symptoms. Interrupt or reduce VONJO dose in patients with significant diarrhea despite optimal supportive care.

Thrombocytopenia:
VONJO can cause worsening thrombocytopenia. VONJO dosing was reduced due to worsening thrombocytopenia in 2% of patients with pre-existing moderate to severe thrombocytopenia (platelet count <100 x 10⁹/L). VONJO dosing was reduced due to worsening thrombocytopenia in 2% of patients with pre-existing severe thrombocytopenia (platelet count <50 x 10⁹/L).

Monitor platelet count prior to VONJO treatment and as clinically indicated during treatment. Interrupt VONJO in patients with clinically significant worsening of thrombocytopenia that lasts for more than seven days. Restart VONJO at 50% of the last given dose once the toxicity has resolved. If toxicity recurs hold VONJO. Restart VONJO at 50% of the last given dose once the toxicity has resolved.

Prolonged QT interval:
VONJO can cause prolongation of the QTc interval. QTc prolongation of  >500 msec was higher in VONJO-treated patients than in patients in the control arm (1.4% vs 1%). QTc increase from baseline by 60 msec or higher was greater in VONJO-treated patients than in control arm patients (1.9% vs 1%). Adverse reactions of QTc prolongation were reported for 3.8% of VONJO-treated patients and 2% of control arm patients. No cases of torsades de pointes were reported.

Avoid use of VONJO in patients with a baseline QTc of  >480 msec. Avoid use of drugs with significant potential for QTc prolongation in combination with VONJO. Correct hypokalemia prior to and during VONJO treatment. Manage QTc prolongation using VONJO interruption and electrolyte management.

Major Adverse Cardiac Events (MACE):
Another JAK)-inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which VONJO is not indicated.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with VONJO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

Thrombosis:
Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which VONJO is not indicated.

Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Secondary Malignancies:
Another JAK-inhibitor has increased the risk of lymphoma and other malignancies, excluding non-melanoma skin cancer (NMSC) (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which VONJO is not indicated. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with VONJO, particularly in patients with a known malignancy (other than a successfully-treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.

Risk of Infection:
Another JAK-inhibitor has increased the risk of serious infections compared to best available therapy (BAT) in patients with myeloproliferative neoplasms. Serious bacterial, mycobacterial, fungal and viral infections may occur in patients treated with VONJO. Delay starting therapy with VONJO until active serious infections have resolved. Observe patients receiving VONJO for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines.

Interactions with CYP3A4 Inhibitors or Inducers:
Co-administration of VONJO with strong CYP3A4 inhibitors or inducers is contraindicated. Avoid concomitant use of VONJO with moderate CYP3A4 inhibitors or inducers.

Drug interruptions due to an adverse reaction occurred in 27% patients who received VONJO 200 mg twice daily compared to 10% of patients treated with BAT. Dosage reductions due to an adverse reaction occurred in 12% of patients who received VONJO 200 mg twice daily compared to 7% of patients treated with BAT. Permanent discontinuation due to an adverse reaction occurred in 15% of patients receiving VONJO 200 mg twice daily compared to 12% of patients treated with BAT.

Please visit http://www.ctibiopharma.com/vonjo_prescribing_information for full Prescribing Information and the Medication Guide.

About Myelofibrosis
Myelofibrosis is bone marrow cancer that results in formation of fibrous scar tissue and can lead to thrombocytopenia and anemia, weakness, fatigue and an enlarged spleen and liver. Within the United States, there are approximately 21,000 patients with myelofibrosis, 7,000 of which have severe thrombocytopenia (defined as blood platelet counts of less than 50 x 10⁹/L). Severe thrombocytopenia is associated with poor survival and high symptom burden and can occur as a result of disease progression or from drug toxicity with other JAK2 inhibitors, such as JAKAFI and INREBIC.

About CTI BioPharma Corp.
We are a commercial biopharmaceutical company focused on the acquisition, development and commercialization of novel targeted therapies for blood-related cancers that offer a unique benefit to patients and their healthcare providers. CTI has one FDA-approved product, VONJO^® (pacritinib).

VONJO^® is a registered trademark of CTI BioPharma Corp.

Forward-Looking Statements
Statements included in this press release that are not historical in nature are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and the Private Securities Litigation Reform Act of 1995. These forward-looking statements, including plans to present data on pacritinib's anemia benefit at later scientific conferences or in scientific journals and the Company's goal of becoming a market leader in cytopenic myelofibrosis, are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: our ability to successfully commercialize VONJO and generate future revenues with respect to VONJO; our limited experience in generating revenue from product sales; the accuracy of our assumptions regarding our planned expenditures and sufficiency of our cash to fund operations; risks and uncertainties related to the COVID-19 pandemic as it relates to our operations and ongoing clinical trials; and those risks more fully discussed in the section entitled "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2021 and subsequent quarterly reports on Form 10-Q. These forward-looking statements speak only as of the date hereof and we assume no obligation to update these forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. "CTI BioPharma" and the CTI BioPharma logo are registered trademarks or trademarks of CTI BioPharma Corp. in various jurisdictions. All other trademarks belong to their respective owner.

CTI BioPharma Investor Contacts:
Argot Partners
+212-600-1902
cti@argotpartners.com

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