On November 7, 2022 Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported financial results for the third quarter of 2022 and highlighted recent corporate achievements (Press release, Day One, NOV 7, 2022, View Source [SID1234623237]).

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"Day One’s progress in 2022 has been remarkable. We announced positive interim results from our pivotal FIREFLY-1 study with tovorafenib in relapsed or progressive pLGG in patients harboring activating RAF alterations, completed a follow-on public offering, advanced our pivotal Phase 3 FIREFLY-2/LOGGIC trial for frontline pLGG as well as our Phase 2 FIRELIGHT-1 trial for MAPK-altered solid tumors, and recently entered into a CRADA agreement with the NCI to further expand therapeutic research opportunities using tovorafenib," said Jeremy Bender, Ph.D., chief executive officer of Day One. "With this significant momentum, we believe we are well-positioned to continue to execute on our mission. We look forward to the topline results from the full FIREFLY-1 pivotal study population, expected in the first quarter of 2023, and potential subsequent NDA submission to the FDA. 2023 is poised to be another pivotal year for Day One."

Program Highlights

Pivotal FIREFLY-1 trial of tovorafenib in relapsed or progressive pLGG in patients harboring activating RAF alterations continues to progress following positive initial data from the first 25 patients announced in June 2022.

Additional interim results from FIREFLY-1 will be presented at the Society for Neuro-Oncology (SNO) annual meeting in November 2022.

Day One is conducting a pivotal Phase 3 clinical trial (FIREFLY-2/LOGGIC) evaluating tovorafenib as a front-line therapy for patients newly diagnosed with pLGG.

The study is a randomized, monotherapy, open-label trial aiming to enroll approximately 400 patients aged 6 months to 25 years across approximately 100 sites globally, including in the United States, Europe and Asia.

The primary endpoint will be the ORR based upon Response Assessment for Neuro-Oncology (RANO) criteria as reported by Blinded Independent Central Review.

Secondary endpoints will include safety, progression-free survival, overall survival, duration of response, functional outcomes and quality of life measures.

Patient enrollment continues in the Phase 2 FIRELIGHT-1 trial evaluating tovorafenib as a monotherapy and as a combination with the company’s investigational MEK inhibitor, pimasertib, in adults and adolescents with recurrent, progressive, or refractory solid tumors harboring MAPK pathway aberrations.

Day One recently entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute’s (NCI) Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program (CTEP) to expand therapeutic research opportunities using tovorafenib.
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NCI investigators will have the opportunity to study tovorafenib in CTEP-sponsored trials to be conducted by NCI-funded extramural clinical networks in several solid tumor and hematologic cancers.

The company also recently announced a global collaboration with Foundation Medicine to develop FoundationOneCDx as a companion diagnostic for tovorafenib.

Corporate Highlights and Upcoming Milestones

Garry Nicholson was appointed as chairman of Day One’s board of directors. Mr. Nicholson brings more than 30 years of pharmaceutical and biotech oncology experience and previously served as president of Pfizer Oncology where he led its global oncology franchise.

Day One strengthened its leadership team with the appointment of Adam Dubow as general counsel. Mr. Dubow joins Day One following a 22-year tenure at Bristol Myers Squibb, where he most recently served as chief compliance and ethics officer and a member of the company’s management team.

Day One anticipates releasing topline results for the full FIREFLY-1 pivotal study population in the first quarter of 2023. If the data are supportive, Day One expects to submit a new drug application (NDA) to the United States Food and Drug Administration (FDA) in the first half of 2023.

Day One expects to dose the first patient in FIREFLY-2/LOGGIC trial in the fourth quarter of 2022.

Third Quarter 2022 Financial Highlights

Cash Position: Cash, cash equivalents and short-term investments totaled $374.3 million on September 30, 2022. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2025.

R&D Expenses: Research and development expenses were $22.0 million for the third quarter of 2022 compared to $9.8 million for the third quarter of 2021. The increase was primarily due to additional employee compensation costs, clinical trial and pre-commercial manufacturing activities related to Day One’s lead product candidate, tovorafenib.

G&A Expenses: General and administrative expenses were $17.7 million for the third quarter of 2022 compared to $9.4 million for the third quarter of 2021. The increase was primarily due to additional employee compensation costs, an ongoing commercial buildout, and professional service expenses to support company growth.

Net Loss: Net loss totaled $37.8 million for the third quarter of 2022 compared to $19.2 million for the third quarter of 2021 with non-cash stock compensation expense of $8.6 million and $5.1 million for the third quarters of 2022 and 2021, respectively.

Upcoming Events

Society for Neuro-Oncology (SNO) annual meeting, November 16-20, 2022

34th Annual Piper Sandler Healthcare Conference, November 29–December 1, 2022

Inducement Grants

In connection with Mr. Dubow’s appointment as general counsel, the compensation committee of the company’s board of directors granted Mr. Dubow 47,400 restricted stock units (RSUs) and 309,000 options to purchase shares of the company’s common stock on October 31, 2022 pursuant to the terms of the Company’s 2022 Equity Inducement Plan. The grants of the RSUs and options were approved by the compensation committee as inducements to Mr. Dubow commencing employment with Day One, in accordance with Nasdaq Marketplace Rule 5635(c)(4). The RSUs vest as to 25% on the first anniversary of the first Quarterly Vesting Date (as defined below), and 1/12th of the remaining RSUs will vest quarterly thereafter, on each applicable quarterly vesting date. For purposes of this announcement, "Quarterly Vesting Date" means February 15, May 15, August 15 or November 15. Each RSU is subject to the terms and conditions of the 2022 Equity Inducement Plan and restricted stock unit agreement covering the grant. The options have an exercise price per share equal to the closing selling price as reported on the Nasdaq Stock Market for the grant date. 1/4th of the options vest and become exercisable on the one-year anniversary of the grant date, and 1/48th of the options vest and become exercisable on a monthly basis thereafter, in each case, so long as the employee remains employed by Day One through the applicable vesting date. The options have a ten-year term and are subject to the terms and conditions of the 2022 Equity Inducement Plan and stock option agreement covering the grant.

About Tovorafenib

Tovorafenib is an investigational, oral, brain-penetrant, highly selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors and solid tumors harboring activating RAF alterations. Tovorafenib has been studied in over 325 patients to date. Currently tovorafenib is under evaluation in a pivotal Phase 2 clinical trial (FIREFLY-1) among pediatric, adolescent and young adult patients with relapsed or progressive pediatric low-grade glioma (pLGG), which is an area of considerable unmet need with no approved therapies for the majority of patients. Day One has also initiated a pivotal Phase 3 study (FIREFLY-2/LOGGIC) in newly-diagnosed patients with pLGG. Beyond pLGG, tovorafenib is being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1). Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma.

About Pimasertib

Pimasertib is an investigational, oral, highly selective, small molecule inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK-1/-2) within the MAPK signaling pathway. Pimasertib has been dosed in over 850 patients to date for various tumor types. Preclinical data indicates that the combination of a MEK inhibitor, such as pimasertib, and a type II RAF inhibitor, such as tovorafenib, has synergistic anti-tumor activity.

Day One is conducting a Phase 1b/2 study (FIRELIGHT-1) to evaluate the safety, tolerability, and preliminary efficacy of combining pimasertib with tovorafenib in adolescent and adult patients (≥12 years of age) with recurrent, progressive, or refractory solid tumors with MAPK pathway aberrations.

On November 7, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported that preclinical data for CX-801, its conditionally activated cytokine program, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Boston, Massachusetts (Press release, CytomX Therapeutics, NOV 7, 2022, View Source [SID1234623236]).

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"Interferon alpha is a clinically validated, powerful antitumor agent, but has historically been limited in its clinical use due to toxicity. CX-801, our masked interferon alpha-2b therapeutic candidate, potentially addresses this limitation through a favorable predicted therapeutic index and preferential activity in the tumor micronenvironment," said Marcia P. Belvin, Ph.D., senior vice president and head of research at CytomX Therapeutics. "At the upcoming SITC (Free SITC Whitepaper) Annual Meeting, we will report encouraging preclinical data that support the development of CX-801 based on its single agent activity as well as its enhanced activity when combined with PD-L1 blockade. We plan to explore the clinical potential of CX-801 in tumor types that have traditionally been both responsive and unresponsive to immunotherapy. We look forward to continuing to progress CX-801 towards an investigational new drug application submission in the second half of 2023."

On November 7, 2022 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported that it will host a conference call and live audio webcast on Monday, November 14, 2022 at 4:30 p.m. Eastern Time to discuss financial results for the third quarter ended September 30, 2022 and to provide a business update (Press release, CymaBay Therapeutics, NOV 7, 2022, View Source [SID1234623235]).

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Conference Call Details
To access the live conference call, please dial 855-327-6837 from the U.S. and Canada, or 631-891-4304 internationally, Conference ID #10020554. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source

On November 7, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the Company along with its collaborative partners will be presenting three posters at the upcoming 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2022) being held in Boston, MA and virtually from November 8th to November 12th (Press release, Curis, NOV 7, 2022, View Source [SID1234623234]).

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"We are pleased to have three posters at SITC (Free SITC Whitepaper) this year," said James Dentzer, President and Chief Executive Officer of Curis. "The presentation on emavusertib follows prior research demonstrating emavusertib reaching therapeutic concentrations in brain metastases and how emavusertib might be useful in helping patients with melanoma that has metastasized to the brain by enhancing the effect of anti-PD1 therapy. Two presentations on CI-8993 describe work on our anti-VISTA antibody’s pharmacokinetic and pharmacodynamic profile in the clinic and Curis’s investigation of potential biomarkers to help guide therapy."

Presentations
Emavusertib
Abstract Title: Immune modulation of melanoma brain metastases by IRAK-4 inhibition
Abstract Number: 1111
Session Type/Title: Poster/Immune-stimulants and immune modulators
Session Date and Time: Thursday, November 10, 11:40 a.m.-1:10 p.m. & 7:30 p.m.-9:00 p.m. ET
CI-8993
Abstract Title: Pharmacokinetic and pharmacodynamic data from a Phase 1 Study of CI-8993 Anti-VISTA Antibody in Patients with Advanced Solid Tumors
Abstract Number: 761
Session Type/Title: Poster/Clinical Trials in Progress
Session Date and Time: Thursday, November 10, 11:40 a.m.-1:10 p.m. & 7:30 p.m.-9:00 p.m. ET

Abstract Title: Development of VISTA-centric tumor immunophenotyping as a novel approach for identification of potential biomarkers for anti-VISTA therapy
Abstract Number: 20
Session Type/Title: Poster/ Biomarkers, Immune Monitoring and Novel Technologies
Session Date and Time: Friday, November 11, 11:55 a.m.-1:25 p.m. & 7:00 p.m.-8:30 p.m. ET
About Emavusertib (CA-4948)
Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-κB protein complex. Additionally, third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, emavusertib was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS.

About CI-8993
CI-8993 is a monoclonal IgG1κ antibody with active Fc, designed to antagonize the V-domain Ig suppressor of T-cell activation (VISTA) signaling pathway. VISTA is a novel negative checkpoint ligand expressed on myeloid cells and T cells that is homologous to PD-1/PD-L1. VISTA enhances T cell quiescence and myeloid derived immune suppressor cells (MDSCs). CI-8993 relieves negative regulation by hematopoietic cells and enhances protective anti-tumor immunity. Preclinically, VISTA monoclonal antibody treatment increased the number of tumor-specific T cells in the periphery, and enhanced the infiltration, proliferation and effector function of tumor-reactive T cells within the tumor microenvironment (TME). VISTA blockade alters the suppressive feature of the TME by decreasing the presence of monocytic and granulocytic MDSCs and increasing the presence of activated dendritic cells (DCs) within the TME leading to enhanced T cell mediated immunity. VISTA monoclonal antibody administration as a monotherapy has been shown to suppress the growth of both transplantable and inducible melanoma in preclinical models. CI-8993 was originally developed as part of a license and collaboration agreement between ImmuNext and Janssen Biotech, Inc (Janssen). In 2016, Janssen initiated clinical development of CI-8993 in a Phase 1 study of CI-8993 in patients with advanced solid tumors. The study enrolled 12 patients, in which one patient experienced dose-limiting side effects related to cytokine release syndrome. Afterwards, Janssen opted to close the study and ImmuNext regained control of the asset. Curis is engaged in a collaboration with ImmuNext for the development of CI-8993.

On November 7, 2022 CTI BioPharma Corp. (Nasdaq: CTIC) reported its financial results for the third quarter ended September 30, 2022 (Press release, CTI BioPharma, NOV 7, 2022, View Source [SID1234623233]).

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"In the third quarter, CTI continued to make strong progress with the U.S. commercial launch of VONJO, delivering net revenue of $18.2 million, a 48% increase in sales compared to the second quarter. This important result reflects strong growth in new patient starts and high refill rates. As CTI continues on its path to becoming the market leader in cytopenic myelofibrosis, the value proposition of VONJO as a safe, simple and effective therapy is rapidly being accepted in both the community and academic settings," said Adam Craig, President and Chief Executive Officer of CTI BioPharma. "As our understanding of pacritinib’s potential mechanisms of actions expands, we are excited to present new data on pacritinib’s anemia benefit in cytopenic myelofibrosis, a benefit believed to be due to ACVR1 (ALK2) inhibition, during an oral presentation at the upcoming ASH (Free ASH Whitepaper) 2022 meeting."

Recent Accomplishments and Updates

Abstract accepted for oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2022 Annual Meeting and Exposition being held December 10–13, 2022, in New Orleans and virtually:
Abstract Title: 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
Two posters selected for poster presentations at ASH (Free ASH Whitepaper) 2022:
Abstract Title: 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
Abstract Title: 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
A new data analysis from the Phase 3 PERSIST-2 trial and an in vitro analysis of pacritinib presented at the Society of Hematologic Oncology (SOHO) 2022 Annual Meeting demonstrated pacritinib as a more potent inhibitor of ACVR1 compared to momelotinib, suggesting an important role of pacritinib in addressing anemia in patients with myelofibrosis. An encore presentation demonstrated full dose pacritinib (200 mg BID) yielded higher response rates and a similar safety profile to lower dose ruxolitinib in patients with myelofibrosis who have moderate or severe thrombocytopenia.
Third Quarter Financial Results
Net product sales of $18.2 million and $32.9 million for the three and nine months ended September 30, 2022, respectively, were entirely attributable to VONJO product sales in the United States. There were no product sales for the comparable periods in 2021. Operating loss was $12.2 million and $23.4 million for the three months ended September 30, 2022 and 2021, respectively, and $66.2 million and $60.0 million for the nine months ended September 30, 2022 and 2021, respectively. The decrease in operating loss between the three-month periods ended September 30, 2022 and 2021 was primarily attributable to net product sales, partially offset by an increase in selling, general and administrative activities related to the commercial launch of VONJO. The increase in operating loss between the nine-month periods ended September 30, 2022 and 2021 resulted primarily from an increase in selling, general and administrative activities related to the commercial launch of VONJO, as well as a $10.3 million milestone expense related to FDA approval of VONJO, which was included in other operating expenses.

Net loss for the three months ended September 30, 2022 was $15.7 million, or $0.13 for basic and diluted loss per share, compared to net loss of $24.2 million, or $0.26 for basic and diluted loss per share, for the same period in 2021. Net loss for the nine months ended September 30, 2022 was $75.5 million, or $0.69 for basic and diluted loss per share, compared to net loss of $61.1 million, or $0.70 for basic and diluted loss per share, for the same period in 2021.

As of September 30, 2022, our cash, cash equivalents and short-term investments totaled $81.6 million, compared to $65.4 million as of December 31, 2021.

Conference Call and Webcast
CTI will host a conference call and webcast to review its third quarter 2022 financial results and provide an update on business activities today, November 7, 2022, at 4:30 p.m. ET. To participate via telephone, please register in advance using this link: https://register.vevent.com/register/BI1dc7f17da2ae4ce8ba0e490c169604ac. Upon registration, telephone participants will receive a confirmation email detailing how to join the conference call, including a dial-in number and a unique registrant ID. A live audio webcast of the event may also be accessed through the "Investors" section of CTI’s website at www.ctibiopharma.com. A replay of the webcast will be available for 30 days following the event.

About VONJO (pacritinib)
Pacritinib is an oral kinase inhibitor with activity against wild type Janus Associated Kinase 2 (JAK2), mutant JAK2V617F form, IRAK1, ACVR1 (ALK2) and 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 × 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).

Important VONJO Safety Information
Hemorrhage:
Serious (11%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <100 × 109/L. Serious (13%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <50 × 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 × 109/L). VONJO dosing was reduced due to worsening thrombocytopenia in 2% of patients with pre-existing severe thrombocytopenia (platelet count <50 × 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 View Source 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 x109/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.