SEATTLE, Sept. 21, 2022 /PRNewswire/ — CTI BioPharma Corp. (NASDAQ: CTIC) right this moment introduced two poster shows from the Firm’s pacritinib program on the Society of Hematologic Oncology (SOHO) Tenth Annual Assembly, to be held in Houston, Texas and nearly September 28 – October 1, 2022.
A brand new information evaluation from the Part 3 PERSIST-2 trial and an in vitro evaluation of pacritinib, a novel JAK2/IRAK1 inhibitor accredited by the U.S. FDA for sufferers with myelofibrosis and a platelet rely under 50 x 109/L, will spotlight pacritinib’s affect on anemia and inhibition of Activin A receptor sort 1 (ACVR1).
“Therapy with pacritinb on the accredited dose of 200 mg twice day by day (BID) led to enhancements in transfusion independence and anemia when in comparison with finest accessible remedy (BAT) in sufferers handled on the PERSIST-2 Part 3 research,” mentioned Dr. Stephen Oh, MD, PhD, Affiliate Professor of Medication, Hematology Division at Washington College College of Medication in St. Louis. “I’m inspired by these information, given the restricted choices to deal with anemia in myelofibrosis, particularly high-risk sufferers with cytopenias who regularly require blood transfusions. I sit up for additional investigation of pacritinib’s potential to alleviate anemia and associated signs on this affected person inhabitants.”
“We’re happy to report that pacritinib is a extremely potent inhibitor of ACVR1. This inhibition is assumed to guide to enhancements in blood transfusion necessities and anemia in sufferers with cytopenic myelofibrosis,” mentioned Adam Craig, MD, PhD, President and Chief Govt Officer of CTI BioPharma. “The info offered at SOHO 2022 assist our perception that pacritinib is a straightforward, secure and efficient JAK2 inhibitor. We plan to current extra information on pacritinib’s anemia profit at a medical assembly later this 12 months.”
Presentation supplies might be accessible at ctibiopharma.com.
Retrospective Evaluation of Anemia Good thing about Pacritinib from the PERSIST-2 Trial
Summary Quantity: MPN-145
Session Title: Poster Session
Session Date: Wednesday, September 28
Presentation Time: 5:05-6:30 p.m. CDT (06:05-7:30 p.m. EDT)
Presenter: Dr. Stephen Oh
Pacritinib is a novel JAK2/IRAK1 inhibitor accredited by the U.S. Meals and Drug Administration (FDA) for sufferers with myelofibrosis and extreme thrombocytopenia (platelet rely <50 x 109/L). Earlier medical trials have famous enhancements in spleen quantity and symptom scores, in addition to enchancment in anemia and a decline in transfusion burden. A retrospective evaluation of the Part 3 PERSIST-2 trial was carried out to additional assess pacritinib’s affect on anemia, and an in vitro evaluation was carried out to discover pacritinib’s inhibition of Activin A receptor sort 1 (ACVR1; also called activin receptor-like kinase 2 [ALK2]).
On duplicate assays, pacritinib was proven to be a stronger inhibitor of ACVR1 in comparison with momelotinib, with a half maximal inhibitory focus (IC50) of 10.8 and 22.6 nM versus34.9 and 70.2 nM, respectively. The share of sufferers who achieved transfusion independence over any 12-week intervals by means of week 24 was larger on pacritinib 200 mg twice day by day than finest accessible remedy (27% vs 7%), amongst evaluable non-transfusion impartial sufferers (outlined as any crimson blood cell transfusions in 90 days previous to the primary dose or a baseline hemoglobin <8 g/dL). These information recommend an vital position for pacritinib in addressing anemia in sufferers with myelofibrosis.
Retrospective Comparability of Affected person Outcomes on Pacritinib Versus Ruxolitinib in Sufferers with Myelofibrosis (MF) and Thrombocytopenia (encore)
Summary Quantity: MPN-141
Session Title: Poster Session
Session Date: Wednesday, September 28
Presentation Time: 5:05-6:30 p.m. CDT (06:05-7:30 p.m. EDT)
Presenter: Dr. Prithviraj Bose
Pacritinib is a novel JAK2/IRAK1 inhibitor accredited by the U.S. FDA for sufferers with myelofibrosis and extreme thrombocytopenia (platelet rely <50 x 109/L). In contrast to the JAK 1/2 inhibitor ruxolitinib, which have to be dose-reduced or held in sufferers with thrombocytopenia, pacritinib has been studied at full dose no matter platelet rely. This retrospective evaluation reported on the outcomes in sufferers handled with pacritinib versus ruxolitinib within the Part 3 PERSIST-2 research. Sufferers have been randomized 1:1:1 to pacritinib 200 mg BID, pacritinib 400 mg as soon as day by day (QD) or BAT, with 45 % of sufferers on BAT receiving ruxolitinib.
Outcomes present that pacritinib, administered on the full dose of 200 mg BID, yielded increased response charges and an analogous security profile in comparison with lower-dose ruxolitinib in sufferers with myelofibrosis who’ve average or extreme thrombocytopenia.
About VONJO (pacritinib)
Pacritinib is an oral kinase inhibitor with exercise towards wild sort Janus Related Kinase 2 (JAK2), mutant JAK2V617F kind and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of quite a lot of cytokines and progress components which might be vital for hematopoiesis and immune perform. Myelofibrosis is usually related to dysregulated JAK2 signaling. Pacritinib has increased inhibitory exercise for JAK2 over different relations, JAK3 and TYK2. At clinically related concentrations, pacritinib doesn’t inhibit JAK1. Pacritinib displays inhibitory exercise towards extra mobile kinases (corresponding to CSF1R and IRAK1), the medical relevance of which is unknown.
VONJO is indicated for the remedy of adults with intermediate or high-risk major or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet rely under 50 × 109/L. This indication is accredited underneath accelerated approval primarily based on spleen quantity discount. Continued approval for this indication could also be contingent upon verification and outline of medical profit in a confirmatory trial(s).
Necessary VONJO Security Data
Severe (11%) and deadly (2%) hemorrhages have occurred in VONJO-treated sufferers with platelet counts <100 × 109/L. Severe (13%) and deadly (2%) hemorrhages have occurred in VONJO-treated sufferers with platelet counts <50 × 109/L. Grade ≥3 bleeding occasions (outlined as requiring transfusion or invasive intervention) occurred in 15% of sufferers handled with VONJO in comparison with 7% of sufferers handled on the management arm. Resulting from hemorrhage, VONJO dose reductions, dose interruptions, or everlasting discontinuations occurred in 3%, 3%, and 5% of sufferers, respectively.
Keep away from use of VONJO in sufferers with energetic bleeding and maintain VONJO seven days previous to any deliberate surgical or invasive procedures. Assess platelet counts periodically, as clinically indicated. Handle hemorrhage utilizing remedy interruption and medical intervention.
VONJO causes diarrhea in roughly 48% of sufferers in comparison with 15% of sufferers handled on the management arm. The median time to decision in VONJO-treated sufferers was two weeks. The incidence of reported diarrhea decreased over time, with 41% of sufferers reporting diarrhea within the first eight weeks of remedy, 15% in weeks 8 by means of 16, and eight% in weeks 16 by means of 24. Diarrhea resulted in remedy interruption in 3% of VONJO-treated sufferers. Not one of the VONJO-treated sufferers reported diarrhea that resulted in remedy discontinuation. Severe diarrhea opposed reactions occurred in 2% of sufferers handled with VONJO in comparison with no such opposed reactions in sufferers within the management arm.
Management pre-existing diarrhea earlier than beginning VONJO remedy. Handle diarrhea with antidiarrheal medicines, fluid alternative, and dose modification. Deal with diarrhea with antidiarrheal medicines promptly on the first onset of signs. Interrupt or scale back VONJO dose in sufferers with important diarrhea regardless of optimum supportive care.
VONJO may cause worsening thrombocytopenia. VONJO dosing was decreased attributable to worsening thrombocytopenia in 2% of sufferers with pre-existing average to extreme thrombocytopenia (platelet rely <100 × 109/L). VONJO dosing was decreased attributable to worsening thrombocytopenia in 2% of sufferers with pre-existing extreme thrombocytopenia (platelet rely <50 × 109/L).
Monitor platelet rely previous to VONJO remedy and as clinically indicated throughout remedy. Interrupt VONJO in sufferers with clinically important worsening of thrombocytopenia that lasts for greater than seven days. Restart VONJO at 50% of the final given dose as soon as the toxicity has resolved. If toxicity recurs maintain VONJO. Restart VONJO at 50% of the final given dose as soon as the toxicity has resolved.
Extended QT interval:
VONJO may cause prolongation of the QTc interval. QTc prolongation of >500 msec was increased in VONJO-treated sufferers than in sufferers within the management arm (1.4% vs 1%). QTc improve from baseline by 60 msec or increased was larger in VONJO-treated sufferers than in management arm sufferers (1.9% vs 1%). Hostile reactions of QTc prolongation have been reported for 3.8% of VONJO-treated sufferers and a pair of% of management arm sufferers. No circumstances of torsades de pointes have been reported.
Keep away from use of VONJO in sufferers with a baseline QTc of >480 msec. Keep away from use of medication with important potential for QTc prolongation together with VONJO. Right hypokalemia previous to and through VONJO remedy. Handle QTc prolongation utilizing VONJO interruption and electrolyte administration.
Main Hostile Cardiac Occasions (MACE):
One other JAK)-inhibitor has elevated the danger of MACE, together with cardiovascular loss of life, myocardial infarction, and stroke (in comparison with these handled with TNF blockers) in sufferers with rheumatoid arthritis, a situation for which VONJO will not be indicated.
Take into account the advantages and dangers for the person affected person previous to initiating or persevering with remedy with VONJO, notably in sufferers who’re present or previous people who smoke and sufferers with different cardiovascular threat components. Sufferers must be knowledgeable concerning the signs of great cardiovascular occasions and the steps to take in the event that they happen.
One other JAK-inhibitor has elevated the danger of thrombosis, together with deep venous thrombosis, pulmonary embolism, and arterial thrombosis (in comparison with these handled with TNF blockers) in sufferers with rheumatoid arthritis, a situation for which VONJO will not be indicated.
Sufferers with signs of thrombosis must be promptly evaluated and handled appropriately.
One other JAK-inhibitor has elevated the danger of lymphoma and different malignancies, excluding non-melanoma pores and skin most cancers (NMSC) (in comparison with these handled with TNF blockers), in sufferers with rheumatoid arthritis, a situation for which VONJO will not be indicated. Sufferers who’re present or previous people who smoke are at extra elevated threat.
Take into account the advantages and dangers for the person affected person previous to initiating or persevering with remedy with VONJO, notably in sufferers with a recognized malignancy (apart from a successfully-treated NMSC), sufferers who develop a malignancy, and sufferers who’re present or previous people who smoke.
Danger of An infection:
One other JAK-inhibitor has elevated the danger of great infections in comparison with finest accessible remedy (BAT) in sufferers with myeloproliferative neoplasms. Severe bacterial, mycobacterial, fungal and viral infections might happen in sufferers handled with VONJO. Delay beginning remedy with VONJO till energetic critical infections have resolved. Observe sufferers receiving VONJO for indicators and signs of an infection and handle promptly. Use energetic surveillance and prophylactic antibiotics in response to medical tips.
Interactions with CYP3A4 Inhibitors or Inducers:
Co-administration of VONJO with robust CYP3A4 inhibitors or inducers is contraindicated. Keep away from concomitant use of VONJO with average CYP3A4 inhibitors or inducers.
Drug interruptions attributable to an opposed response occurred in 27% sufferers who acquired VONJO 200 mg twice day by day in comparison with 10% of sufferers handled with BAT. Dosage reductions attributable to an opposed response occurred in 12% of sufferers who acquired VONJO 200 mg twice day by day in comparison with 7% of sufferers handled with BAT. Everlasting discontinuation attributable to an opposed response occurred in 15% of sufferers receiving VONJO 200 mg twice day by day in comparison with 12% of sufferers handled with BAT.
Please go to http://www.ctibiopharma.com/vonjo_prescribing_information for full Prescribing Data and the Remedy Information.
Myelofibrosis is bone marrow most cancers that leads to formation of fibrous scar tissue and might result in thrombocytopenia and anemia, weak point, fatigue and an enlarged spleen and liver. Inside the US, there are roughly 21,000 sufferers with myelofibrosis, 7,000 of which have extreme thrombocytopenia (outlined as blood platelet counts of lower than 50 x109/L). Extreme thrombocytopenia is related to poor survival and excessive symptom burden and might happen because of illness development or from drug toxicity with different JAK2 inhibitors, corresponding to JAKAFI and INREBIC.
About CTI BioPharma Corp.
We’re a industrial biopharmaceutical firm targeted on the acquisition, growth and commercialization of novel focused therapies for blood-related cancers that supply a novel profit to sufferers and their healthcare suppliers. CTI has one FDA-approved product, VONJO® (pacritinib), a JAK2 and IRAK1 inhibitor, that spares JAK1. VONJO is accredited for the remedy of adults with intermediate- or high-risk major or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet rely under 50 × 109/L. This indication is accredited underneath FDA accelerated approval primarily based on spleen quantity discount. Continued approval for this indication could also be contingent upon verification and outline of medical profit in a confirmatory trial(s). CTI is conducting the Part 3 PACIFICA research of VONJO in sufferers with myelofibrosis and extreme thrombocytopenia as a post-marketing requirement.
VONJO® is a registered trademark of CTI BioPharma Corp.
Statements included on this press launch that aren’t historic in nature are forward-looking statements inside the that means of Part 27A of the Securities Act of 1933 and Part 21E of the Securities Trade Act of 1934, and the Non-public Securities Litigation Reform Act of 1995. These forward-looking statements are primarily based on present assumptions that contain dangers, uncertainties and different components which will trigger the precise outcomes, occasions or developments to be materially completely different from these expressed or implied by such forward-looking statements. These dangers and uncertainties embody, however should not restricted to: our skill to efficiently commercialize VONJO and generate future revenues with respect to VONJO; our restricted expertise in producing income from product gross sales; the accuracy of our assumptions relating to our deliberate expenditures and sufficiency of our money to fund operations; dangers and uncertainties associated to the COVID-19 pandemic because it pertains to our operations and ongoing medical trials; plans to current extra information on pacritinib’s anemia profit at later scientific conferences or in scientific journals; and people dangers extra totally mentioned within the part entitled “Danger Elements” in our Annual Report on Kind 10-Okay for the 12 months ended December 31, 2021 and subsequent quarterly experiences on Kind 10-Q. These forward-looking statements communicate solely as of the date hereof and we assume no obligation to replace these forward-looking statements, and readers are cautioned to not place undue reliance on such forward-looking statements. “CTI BioPharma” and the CTI BioPharma emblem are registered logos or logos of CTI BioPharma Corp. in varied jurisdictions. All different logos belong to their respective proprietor.
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