On December 10, 2022 CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported an oral, encore presentation of clinical data from patients with sickle cell disease (SCD) or transfusion-dependent beta-thalassemia (TDT) treated with the investigational therapy exagamglogene autotemcel (exa-cel) in CLIMB-111 or CLIMB-121 and followed in CLIMB-131, a long-term follow-up study (Press release, CRISPR Therapeutics, DEC 10, 2022, View Source [SID1234625015]). Vertex will also present new health economics and outcomes research from multiple studies in patients with SCD and TDT.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to be at ASH (Free ASH Whitepaper) and share data from the pivotal exa-cel trials and from multiple real-world studies examining the burden of severe SCD and TDT," said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. "We remain on track to complete submission of the first ever CRISPR-based therapy in the EU and U.K. this year, and we have initiated our rolling submission in the U.S., which we plan to complete in Q1 2023. We are working with urgency to bring forward this potential therapy to patients who are waiting."

Vertex will have the following presentations at ASH (Free ASH Whitepaper) this year.

Oral presentation, abstract #12 combined with abstract #2137, in partnership with CRISPR Therapeutics, entitled "Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Transfusion-Dependent Beta-Thalassemia and Severe Sickle Cell Disease," will be presented on Saturday, December 10 at 10:45 a.m CST. The presentation will include encore data as presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2022 on patients with SCD or TDT who received the investigational therapy exa-cel in the CLIMB-111 or CLIMB-121 study and were followed in CLIMB-131, a long-term follow-up study.
Oral presentation, abstract #577, entitled "Health-Related Quality of Life, Disease Impacts, and Health Equity Concerns in Adults with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises: Preliminary Results from a Global Longitudinal Survey," will be presented on Sunday, December 11 at 12:00 p.m. CST. The study quantifies the symptoms, quality of life and work impacts of living with SCD with recurrent vaso-occlusive crises (VOCs). This presentation represents preliminary results from an ongoing longitudinal study.
Poster presentation, abstract #4820, entitled "Clinical and Economic Outcomes in Patients with Transfusion-Dependent Beta-Thalassemia and Patients with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises Receiving Hematopoietic Stem Cell Transplants in the United States," will be presented on Monday, December 12 from 6:00-8:00 p.m. CST. The study analyzes the demographics, transplant-related complications and costs of patients with SCD and TDT who undergo a hematopoietic stem cell transplant (HSCT) in the United States utilizing a claims database.
Poster presentation, abstract #4882, entitled "Health-Related Quality of Life and Disease Impacts in Adults with Transfusion-Dependent Beta-Thalassemia: Preliminary Results from the Global Longitudinal Survey," will be presented on Monday, December 12 from 6:00-8:00 p.m. CST. The study quantifies the symptoms, quality of life and work impacts of living with TDT. This presentation represents preliminary results from an ongoing longitudinal study.
The accepted abstracts are available online on the ASH (Free ASH Whitepaper) website.

About exagamglogene autotemcel (exa-cel)

Exa-cel, formerly known as CTX001, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with SCD or TDT, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exa-cel has the potential to reduce or eliminate painful and debilitating VOCs for patients with SCD and alleviate transfusion requirements for patients with TDT. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021 and presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2022.

Based on progress in this program to date, exa-cel has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both SCD and TDT. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both SCD and TDT.

The companies have begun the rolling Biologics License Application (BLA) submission for exa-cel to the U.S. FDA and plan to complete the BLA by the end of the first quarter 2023 and remain on track to submit exa-cel to the Medicines and Healthcare products Regulatory Agency in the U.K. and the EMA in the European Union by the end of the year.

About CLIMB‑111 and CLIMB‑121

The ongoing Phase 1/2/3 open-label trials, CLIMB‑111 and CLIMB‑121, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after exa-cel infusion. Each patient will be asked to participate in CLIMB‑131, a long-term follow-up trial.

About CLIMB-131

The ongoing long-term, open-label trial, CLIMB-131, is designed to evaluate the safety and efficacy of exa-cel in patients who received exa-cel in CLIMB‑111, CLIMB‑121, CLIMB‑141, CLIMB‑151 or CLIMB-161. The trial is designed to follow participants for up to 15 years after exa-cel infusion.

About CLIMB‑141 and CLIMB‑151

The ongoing Phase 3 open-label trials, CLIMB‑141 and CLIMB‑151, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years and will plan to extend to ages 2 to less than 5 years at a later date. Each trial will enroll approximately 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.

About CLIMB-161

The ongoing Phase 3b study, CLIMB-161, is to support expansion of our manufacturing footprint after initial potential approval and launch. This study will enroll approximately 12 patients with either SCD or TDT ages 12 to 35 years. Patients will be followed for approximately one year after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.

About the Gene-Editing Process in These Trials

Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, exa-cel, will then be infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT), a process which involves a patient being treated with myeloablative busulfan conditioning. Patients undergoing HSCT may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of exa-cel. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of exa-cel on multiple measures of disease and for safety.

On December 10, 2022 AbbVie (NYSE: ABBV) reported new and updated data across clinical and real-world studies in chronic lymphocytic leukemia (CLL) (Press release, AbbVie, DEC 10, 2022, View Source [SID1234625008]). Presentations featured during the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition will include two clinical trials investigating once daily, fixed-duration treatment with IMBRUVICA (ibrutinib) plus VENCLEXTA/VENCLYXTO (venetoclax) (I+V) in adults with CLL and several analyses from real-word data evaluating front-line treatment in CLL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As the only Bruton’s Tyrosine Kinase inhibitor (BTKi) studied across many clinical trials, including up to eight years of follow-up data in CLL and small lymphocytic lymphoma (SLL), these latest data add to overall evidence for IMBRUVICA," said James Dean, M.D., Ph.D., global development lead and executive medical director, Pharmacyclics LLC, an AbbVie company. "These findings further inspire our commitment to the continued investigation of IMBRUVICA in the treatment of patients with CLL."

Presentations will include the five-year median follow-up efficacy and safety data from the minimal residual disease (MRD) Cohort of the Phase 2 CAPTIVATE study (Abstract #92)1 and data on MRD kinetics from the randomized, open-label Phase 3 GLOW study (Abstract #93).2 Additionally, new data from three studies evaluating the impact of IMBRUVICA treatment in the real-world setting will be presented (Abstracts #797,#1809, #3132).3,4,5

Five-Year Update from the CAPTIVATE Study Adds to Clinical Data Investigating the Potential of a Fixed-Duration Regimen

The MRD Cohort of the Phase 2 CAPTIVATE (NCT02910583) study evaluated 164 patients age 70 years or younger with previously untreated CLL; those who achieved confirmed undetectable minimal residual disease (uMRD) after completion of I+V fixed-duration treatment were randomly assigned to placebo (PBO) (n=43), or continued IMBRUVICA treatment (n=43).1 For patients with confirmed uMRD, median time on study was 56 months (PBO arm range, 40‒65 months; IMBRUVICA arm range, 25‒68 months); median post-randomization follow-up was 41 months in both arms.1 At four years of follow-up, estimated progression-free survival (PFS) was 88 percent (95 percent Confidence Interval [CI], 74-95, seven progressive disease events) with PBO compared to 95 percent (95 percent CI, 82-99, two progressive disease events) with continued IMBRUVICA treatment.1 Additionally, at year four, patients in the PBO arm of the study achieved an estimated overall survival (OS) rate of 100 percent compared to 98 percent (95 percent CI, 84-99.7) in the IMBRUVICA treatment arm.1

No new atrial fibrillation (AF) or Grade three or higher hemorrhage events occurred in the PBO arm during the three year post-randomization period, and one patient in the IMBRUVICA arm had AF in the second year post-randomization.1 During the three-year post-randomization period, adverse events (AEs) of any grade for patients treated with IMBRUVICA were arthralgia (4/41), hypertension (2/41), neutropenia (1/41) and diarrhea (1/41). No new grade three or higher hemorrhage events occurred in either arm.1

The Data of IMBRUVICA in the Treatment of CLL Through Real-World Studies

An oral presentation (Abstract #797) will report findings comparing time to next treatment (TTNT) in patients with CLL who received first-line treatment with IMBRUVICA or acalabrutinib based on a real-world study utilizing electronic medical records.3

A poster presentation (Abstract #1809) will highlight results from a pooled analysis of the RESONATE-2 (NCT01722487), ECOG1912 (NCT02048813), and iLLUMINATE (NCT02264574) clinical studies investigating the comparison of OS in previously untreated CLL patients treated with IMBRUVICA to that of the available age-matched general population, as well as comparative results of OS in patients treated with IMBRUVICA versus chemotherapy and chemoimmunotherapy.4

Thirdly, the final analysis from the informCLL real-world (RW) registry, which assessed RW outcomes with first-line IMBRUVICA versus chemoimmunotherapy (CIT) in patients with CLL and SLL, will be presented as a poster (Abstract #3132).5 The informCLL registry enrolled 1,459 patients, of whom 59 percent were previously untreated.5 First-line treatment with IMBRUVICA was associated with longer TTNT than with CIT and sustained benefit, with up to four years of follow-up.5 In the IMBRUVICA cohort (n=383), serious adverse events (AEs) occurred in 144 patients (38 percent), most commonly (greater or equal to three percent of patients) pneumonia (six percent) and atrial fibrillation (five percent); AEs led to discontinuation of IMBRUVICA in 135 patients (35 percent), most commonly atrial fibrillation (five percent) and fatigue (three percent). In the CIT cohort (n=363), serious AEs occurred in 85 patients (23 percent), most commonly febrile neutropenia (four percent) and pneumonia (three percent). AEs led to discontinuation of CIT in 61 patients (17 percent), and no single AE term led to discontinuation in three percent or more of patients (most common was anemia, two percent).5 The spectrum and frequency of AEs observed with first-line treatment appeared consistent with data from clinical studies and other RWE studies.5

About IMBRUVICA
IMBRUVICA (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. IMBRUVICA blocks the Bruton’s tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments and inhibits their proliferation.6,7,8

IMBRUVICA is approved in more than 100 countries and has been used to treat more than 270,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, over 11 years evaluating the efficacy and safety of IMBRUVICA.

IMBRUVICA was first approved by the U.S. Food and Drug Administration (FDA) in November 2013, and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include indications to treat adults with CLL/SLL with or without 17p deletion (del17p), adults with Waldenström’s macroglobulinemia (WM), adults with previously treated mantle cell lymphoma (MCL)*, adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, as well as adult and pediatric patients one year of age and older with previously treated chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.9

*Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

For more information, visit www.IMBRUVICA.com.

IMPORTANT SIDE EFFECT INFORMATION

Before taking IMBRUVICA, tell your healthcare provider about all of your medical conditions, including if you:

have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA for any planned medical, surgical, or dental procedure.
have bleeding problems
have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes
have an infection
have liver problems
are pregnant or plan to become pregnant. IMBRUVICA can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA. Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA.
Females who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA and for 1 month after the last dose.
Males with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA and for 1 month after the last dose.
are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with IMBRUVICA and for 1 week after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA with certain other medicines may affect how IMBRUVICA works and can cause side effects.

How should I take IMBRUVICA?

Take IMBRUVICA exactly as your healthcare provider tells you to take it.
Take IMBRUVICA 1 time a day at about the same time each day.
IMBRUVICA comes as capsules, tablets, and oral suspension.

If your healthcare provider prescribes IMBRUVICA capsules or tablets:
Swallow IMBRUVICA capsules or tablets whole with a glass of water.
Do not open, break, or chew IMBRUVICA capsules.
Do not cut, crush, or chew IMBRUVICA tablets.
If your healthcare provider prescribes IMBRUVICA oral suspension:
See the detailed Instructions for Use that comes with IMBRUVICA oral suspension for information about the correct way to give a dose to your child. If you have questions about how to give IMBRUVICA oral suspension, talk to your healthcare provider.
Do not use if the carton seal is broken or missing.
If you miss a dose of IMBRUVICA take it as soon as you remember on the same day. Take your next dose of IMBRUVICA at your regular time on the next day. Do not take extra doses of IMBRUVICA to make up for a missed dose.
If you take too much IMBRUVICA call your healthcare provider or go to the nearest hospital emergency room right away.
What should I avoid while taking IMBRUVICA?

You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA. These products may increase the amount of IMBRUVICA in your blood.
What are the possible side effects of IMBRUVICA?
IMBRUVICA may cause serious side effects, including:

Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA, and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.
Infections can happen during treatment with IMBRUVICA. These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA.
Heart problems. Serious heart rhythm problems (ventricular arrhythmias, atrial fibrillation and atrial flutter), heart failure and death have happened in people treated with IMBRUVICA, especially in people who have an infection, an increased risk for heart disease, or have had heart rhythm problems in the past. Your heart function will be checked before and during treatment with IMBRUVICA. Tell your healthcare provider if you get any symptoms of heart problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, swelling of the feet, ankles or legs, chest discomfort, or you faint. If you develop any of these symptoms, your healthcare provider may do tests to check your heart and may change your IMBRUVICA dose.
High blood pressure (hypertension). New or worsening high blood pressure has happened in people treated with IMBRUVICA. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
Decrease in blood cell counts. Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA, but can also be severe. Your healthcare provider should do monthly blood tests to check your blood counts.
Second primary cancers. New cancers have happened during treatment with IMBRUVICA, including cancers of the skin or other organs.
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.
The most common side effects of IMBRUVICA in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

· diarrhea

· tiredness

· muscle and bone pain

· rash

· bruising

The most common side effects of IMBRUVICA in adults or children 1 year of age and older with cGVHD include:

· tiredness

· low red blood cell count (anemia)

· bruising

· diarrhea

· low platelet count

· muscle and joint pain

· fever

· muscle spasms

· mouth sores (stomatitis)

· bleeding

· nausea

· stomach pain

· pneumonia

· headache

Diarrhea is a common side effect in people who take IMBRUVICA. Drink plenty of fluids during treatment with IMBRUVICA to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away.

These are not all the possible side effects of IMBRUVICA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of IMBRUVICA
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA for a condition for which it was not prescribed. Do not give IMBRUVICA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA that is written for health professionals.

Please click here for full Prescribing Information.

About VENCLYXTA (venetoclax)
VENCLYXTA (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLYXTA targets the BCL-2 protein and works to help restore the process of apoptosis.

VENCLYXTA is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.

Approved Uses of VENCLEXTA

VENCLEXTA is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with
newly diagnosed acute myeloid leukemia (AML) who:
are 75 years of age or older, or
have other medical conditions that prevent the use of standard chemotherapy.
It is not known if VENCLEXTA is safe and effective in children.

Important Safety Information

What is the most important information I should know about VENCLEXTA?

VENCLEXTA can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS.

You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start treatment and during treatment with VENCLEXTA.

It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS.

Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you have side effects. When restarting VENCLEXTA after stopping for 1 week or longer, your healthcare provider may again check for your risk of TLS and change your dose.

Who should not take VENCLEXTA?

Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased TLS.

Tell your healthcare provider about all the medicines you take, including prescription and over-the- counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider.
Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you:

have kidney or liver problems.
have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium.
have a history of high uric acid levels in your blood or gout.
are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during, or after treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA. If you become pregnant or think you are pregnant, tell your healthcare provider right away.
are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk.
Do not breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.
What should I avoid while taking VENCLEXTA?

You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?

VENCLEXTA can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your healthcare provider will do blood tests to check your blood counts during treatment with VENCLEXTA and may pause dosing.
Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with VENCLEXTA. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with VENCLEXTA.
Tell your healthcare provider right away if you have a fever or any signs of an infection during treatment with VENCLEXTA.

The most common side effects of VENCLEXTA when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell counts; low platelet counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your arms, legs, hands, and feet.

The most common side effects of VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of VENCLEXTA. Call your doctor for medical advice about side effects.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you cannot afford your medication, contact genentech-access.com/patient/brands/venclexta for assistance.

On December 10, 2022 AbbVie (NYSE: ABBV) reported new data from Cohort 3 of its Phase 2 REFINE study of investigational navitoclax in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (MF) (Press release, AbbVie, DEC 10, 2022, View Source [SID1234625007]). The exploratory analysis suggests the combination of navitoclax and ruxolitinib led to reductions in bone marrow fibrosis (BMF) and variant allele frequency (VAF) for common genetic mutations found in individuals with myelofibrosis that may indicate potential disease modification.1 The findings were shared in an oral presentation (abstract #237) at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"While the current standard of care for patients with myelofibrosis can improve disease symptoms, impact on underlying disease biology is limited. It is our hope that patients have an option that goes beyond symptom control," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology clinical development, AbbVie. "Consistent with previous evidence, these results suggest navitoclax combination may have disease modifying potential, both as an anti-fibrosis agent and by reducing variant allele frequency of driver mutations."

REFINE (NCT03222609) is a Phase 2 non-randomized open-label multi-cohort study evaluating the safety and efficacy of navitoclax alone or in combination with ruxolitinib in MF.2

These data build on AbbVie’s history of transforming standards of care in blood cancers, including recent presentations of investigational navitoclax data from the REFINE study earlier this year at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

The findings presented at ASH (Free ASH Whitepaper) were based on an exploratory analysis of 32 JAK inhibitor-naïve patients with MF from Cohort 3 of the Phase 2 REFINE study. The primary endpoint was spleen volume reduction of ≥35 percent (SVR35) from baseline at week 24.1 Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF and a reduction in VAF for the driver gene mutations (JAK2V617, CALR, MPL or Triple-negative), respectively.1

In this exploratory analysis, SVR35 at week 24 was observed in higher-risk groups, improving over time. The four poor prognosis subgroups were: Type (primary or secondary) of MF (primary MF, 59 percent [n = 10/17]; age (≥75 years, 50 percent [n = 4/8]); prognostic risk score, as measured by Dynamic International Prognostic Scoring System or DIPSS (intermediate-2, 63 percent [n = 12/19]; high, 33 percent [n = 1/3]); and presence of high molecular risk (HMR) mutations (47 percent [n = 9/19].1

In Cohort 3, BMF grade improvement was evaluable in 81 percent (26/32) of patients.1 Of these study participants, 35 percent (9/26) achieved ≥ 1 grade improvement at any time during treatment with a median time-to-improvement of 12.3 weeks.1 Complete resolution of BMF was observed in 22 percent (2/9) of patients.1

Reduction in driver gene mutation VAF > 20% from baseline at week 12 or 24 was observed in 50 percent (14/28) of patients, while 18 percent (5/28) of patients achieved > 50% VAF reduction from baseline. There were no differences in > 20% VAF reductions from baseline to week 12 or 24 between those with or without HMR mutations (47 percent [7/15] versus 54 percent [7/13], respectively).

Preliminary safety analysis identified no new safety signals. Twenty-five (78 percent) patients reported one or more adverse events (AE). The most common grade ≥3 AEs were thrombocytopenia (47 percent), anemia (34 percent), and neutropenia (25 percent). 9.4 percent of patients discontinued therapy due to an AE.3

"These results are promising for patients who need a treatment option that goes beyond just symptom control," said Francesco Passamonti, full professor of hematology, University of Insubria and chief, hematology, Varese Hospital, Italy. "The suggestion of disease modification in this analysis from combination therapy with navitoclax is encouraging, particularly when combined with clinical efficacy in terms of SVR35 rates in the higher risk groups that improved over time."

About Navitoclax
Navitoclax is an investigational, oral BCL-XL/BCL-2 inhibitor. Navitoclax is not approved by any health authority worldwide at this time. Its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies.

AbbVie has an extensive late-stage clinical trial program for investigational navitoclax that is currently enrolling. Please visit us here for more information about enrolling in a clinical trial.

About the REFINE Study
REFINE is a multi-cohort, Phase 2, randomized, open-label, multicenter study evaluating the tolerability and efficacy of navitoclax alone or when added to ruxolitinib in patients with myelofibrosis (MF).2 The primary outcome measure is the percentage of patients who achieve spleen volume reduction of greater than or equal to 35 percent (SVR35) from baseline to week 24.2 Secondary outcomes measures include percentage of participants achieving 50 percent reduction in total symptom score from baseline to week 24; anemia response every 12 weeks up to approximately 96 weeks, measured according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria; and change in grade of bone marrow fibrosis assessed according to the European Consensus Grading System.2

Data presented at ASH (Free ASH Whitepaper) 2022 include safety and efficacy results from Cohort 3 of REFINE (n=32). Patients in Cohort 3 had primary or secondary MF with splenomegaly (DIPSS ≥ intermediate-1) and had not received JAK-2 therapy or bromodomain and extra terminal motif (BET) inhibitors prior to enrollment. The primary endpoint of SVR35 was assessed by MRI conducted by central review. Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF obtained from BM biopsies by local evaluation and a reduction in VAF for the driver gene mutations (JAK2V617, CALR, or MPL), respectively. Studied HMR mutations included ASXL1, EZH2, SRSF2, IDH1/2, and U2AF1 p.Q157. Driver gene VAF and HMR mutations were determined in whole blood with a 50-gene focus myeloid next-generation sequencing panel. The findings presented at ASH (Free ASH Whitepaper) 2022 are representative of data from Cohort 3 of the REFINE study as of February 7, 2022.

More information about the REFINE study can be found at View Source (NCT03222609).

About Myelofibrosis
Myelofibrosis (MF) is a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Patients living with MF experience symptoms such as an enlarged spleen, fatigue, weakness, and severe anemia which are often debilitating and greatly impact quality of life. MF also carries a risk of transformation to more aggressive disease such as acute myeloid leukemia.

On December 9, 2022 Takeda (TSE:4502/NYSE:TAK) reported that it will present 15 company-sponsored abstracts at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 10-13, 2022 in New Orleans (Press release, Takeda, DEC 10, 2022, View Source [SID1234625001]). Takeda’s latest research focuses on improving long-term outcomes for patients with hematologic diseases.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Takeda’s presentations will include oral sessions detailing a three-year update of the Phase 3 OPTIC trial demonstrating the efficacy and safety of ICLUSIG (ponatinib) in patients with resistant chronic-phase chronic myeloid leukemia (CP-CML), and results from a first-in-human Phase 1/2 study evaluating modakafusp alfa (TAK-573) in patients with relapsed / refractory multiple myeloma.

"Our latest research is focused on investigating novel mechanisms of action, as well as optimizing approved treatments to improve long-term outcomes and more deeply understand and address unmet needs for patients across a range of hematologic diseases," said Awny Farajallah, M.D., Head of Global Medical Affairs Oncology at Takeda. "We look forward to sharing our latest clinical trial results and real-world data with the goal of contributing to a more holistic view of the patient experience, and ultimately, profound improvements in care."

A full list of company-sponsored abstracts, which include data in multiple myeloma, lymphoma, leukemia, von Willebrand disease and hemophilia can be found here.

Modakafusp alfa (TAK-573) is an investigational compound that has not been approved for use by the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) or any other regulatory authorities.

About ICLUSIG (ponatinib) tablets
ICLUSIG is a kinase inhibitor targeting BCR::ABL1, an abnormal tyrosine kinase that is expressed in CML and Ph+ ALL. ICLUSIG is a targeted cancer medicine developed using a computational and structure-based drug-design platform, specifically designed to inhibit the activity of BCR::ABL1 and its mutations. ICLUSIG inhibits native BCR::ABL1, as well as all BCR::ABL1 treatment-resistant mutations, including the most resistant T315I mutation. ICLUSIG received full approval from the FDA in November 2016. ICLUSIG is indicated for the treatment of adult patients with chronic-phase (CP) CML with resistance or intolerance to at least two prior kinase inhibitors, accelerated-phase (AP) or blast-phase (BP) CML or Ph+ ALL for whom no other kinase inhibitor is indicated, and T315I+ CML (CP, AP or BP) or T315I-positive Ph+ ALL. ICLUSIG is not indicated and is not recommended for the treatment of patients with newly diagnosed CP-CML.

IMPORTANT SAFETY INFORMATION

WARNING: ARTERIAL OCCLUSIVE EVENTS, VENOUS THROMBOEMBOLIC EVENTS, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning.

Arterial occlusive events (AOEs), including fatalities, have occurred in ICLUSIG-treated patients. AOEs included fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. Monitor for evidence of AOEs. Interrupt or discontinue ICLUSIG based on severity. Consider benefit-risk to guide a decision to restart ICLUSIG.
Venous thromboembolic events (VTEs) have occurred in ICLUSIG-treated patients. Monitor for evidence of VTEs. Interrupt or discontinue ICLUSIG based on severity.
Heart failure, including fatalities, occurred in ICLUSIG-treated patients. Monitor for heart failure and manage patients as clinically indicated. Interrupt or discontinue ICLUSIG for new or worsening heart failure.
Hepatotoxicity, liver failure and death have occurred in ICLUSIG-treated patients. Monitor liver function tests. Interrupt or discontinue ICLUSIG based on severity.

WARNINGS AND PRECAUTIONS
Arterial Occlusive Events (AOEs): AOEs, including fatalities, have occurred in patients who received ICLUSIG in OPTIC and PACE. These included cardiovascular, cerebrovascular, and peripheral vascular events. The incidence of AOEs in OPTIC (45 mg->15 mg) was 14% of 94 patients; 6% experienced Grade 3 or 4. In PACE, the incidence of AOEs was 26% of 449 patients; 14% experienced Grade 3 or 4. Fatal AOEs occurred in 2.1% of patients in OPTIC, and in 2% of patients in PACE. Some patients in PACE experienced recurrent or multisite vascular occlusion. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. The most common risk factors observed with these events in PACE were history of hypertension, hypercholesterolemia, and non-ischemic cardiac disease. In OPTIC and PACE, AOEs were more frequent with increasing age.

In OPTIC, patients with uncontrolled hypertension or diabetes and patients with clinically significant, uncontrolled, or active cardiovascular disease were excluded. In PACE, patients with uncontrolled hypertriglyceridemia and patients with clinically significant or active cardiovascular disease within the 3 months prior to the first dose of ICLUSIG were excluded. Consider whether the benefits of ICLUSIG are expected to exceed the risks.

Monitor for evidence of AOEs. Interrupt, then resume at the same or decreased dose or discontinue ICLUSIG based on recurrence/severity. Consider benefit-risk to guide a decision to restart ICLUSIG.

Venous Thromboembolic Events (VTEs): Serious or severe VTEs have occurred in patients who received ICLUSIG. In PACE, VTEs occurred in 6% of 449 patients including serious or severe (Grade 3 or 4) VTEs in 5.8% of patients. VTEs included deep venous thrombosis, pulmonary embolism, superficial thrombophlebitis, retinal vein occlusion, and retinal vein thrombosis with vision loss. The incidence was higher in patients with Ph+ ALL (9% of 32 patients) and BP-CML (10% of 62 patients). One of 94 patients in OPTIC experienced a VTE (Grade 1 retinal vein occlusion). Monitor for evidence of VTEs. Interrupt, then resume at the same or decreased dose or discontinue ICLUSIG based on recurrence/severity.

Heart Failure: Fatal, serious or severe heart failure events have occurred in patients who received ICLUSIG. In PACE, heart failure occurred in 9% of 449 patients; 7% experienced serious or severe (Grade 3 or higher). Heart failure occurred in 13% of 94 patients in OPTIC; 1.1% experienced serious or severe (Grade 3 or 4). In PACE, the most frequently reported heart failure events (≥2%) were congestive cardiac failure (3.1%), decreased ejection fraction (2.9%), and cardiac failure (2%). In OPTIC, the most frequently reported heart failure events (>1 patient each) were left ventricular hypertrophy (3.2%) and BNP increased (3.2%). Monitor patients for signs or symptoms consistent with heart failure and manage heart failure as clinically indicated. Interrupt, then resume at reduced dose or discontinue ICLUSIG for new or worsening heart failure.

Hepatotoxicity: ICLUSIG can cause hepatotoxicity, including liver failure and death. Fulminant hepatic failure leading to death occurred in 3 patients, with hepatic failure occurring within 1 week of starting ICLUSIG in one of these patients. These fatal cases occurred in patients with BP-CML or Ph+ ALL. Hepatotoxicity occurred in 28% of 94 patients in OPTIC and 32% of 449 patients in PACE. Grade 3 or 4 hepatotoxicity occurred in OPTIC (6% of 94 patients) and PACE (13% of 449 patients). The most frequent hepatotoxic events were elevations of ALT, AST, GGT, bilirubin, and alkaline phosphatase. Monitor liver function tests at baseline, then at least monthly or as clinically indicated. Interrupt, then resume at a reduced dose or discontinue ICLUSIG based on recurrence/severity.

Hypertension: Serious or severe hypertension, including hypertensive crisis, has occurred in patients who received ICLUSIG. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. Monitor blood pressure at baseline and as clinically indicated and manage hypertension as clinically indicated. Interrupt, dose reduce, or stop ICLUSIG if hypertension is not medically controlled. For significant worsening, labile or treatment-resistant hypertension, interrupt ICLUSIG and consider evaluating for renal artery stenosis.

Pancreatitis: Serious or severe pancreatitis has occurred in patients who received ICLUSIG. Elevations of lipase and amylase also occurred. In the majority of cases that led to dose modification or treatment discontinuation, pancreatitis resolved within 2 weeks. Monitor serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on severity. Evaluate for pancreatitis when lipase elevation is accompanied by abdominal symptoms.

Increased Toxicity in Newly Diagnosed Chronic Phase CML: In a prospective randomized clinical trial in the first line treatment of newly diagnosed patients with CP-CML, single agent ICLUSIG 45 mg once daily increased the risk of serious adverse reactions 2-fold compared to single agent imatinib 400 mg once daily. The median exposure to treatment was less than 6 months. The trial was halted for safety. Arterial and venous thrombosis and occlusions occurred at least twice as frequently in the ICLUSIG arm compared to the imatinib arm. Compared to imatinib-treated patients, ICLUSIG-treated patients exhibited a greater incidence of myelosuppression, pancreatitis, hepatotoxicity, cardiac failure, hypertension, and skin and subcutaneous tissue disorders. ICLUSIG is not indicated and is not recommended for the treatment of patients with newly diagnosed CP-CML.

Neuropathy: Peripheral and cranial neuropathy occurred in patients in OPTIC and PACE. Some of these events in PACE were Grade 3 or 4. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Ocular Toxicity: Serious or severe ocular toxicity leading to blindness or blurred vision have occurred in ICLUSIG-treated patients. The most frequent ocular toxicities occurring in OPTIC and PACE were dry eye, blurred vision, and eye pain. Retinal toxicities included age-related macular degeneration, macular edema, retinal vein occlusion, retinal hemorrhage, and vitreous floaters. Conduct comprehensive eye exams at baseline and periodically during treatment.

Hemorrhage: Fatal and serious hemorrhage events have occurred in patients who received ICLUSIG. Fatal hemorrhages occurred in PACE and serious hemorrhages occurred in OPTIC and PACE. In PACE, the incidence of serious bleeding events was higher in patients with AP-CML, BP-CML, and Ph+ ALL. Gastrointestinal hemorrhage and subdural hematoma were the most frequently reported serious hemorrhages. Events often occurred in patients with Grade 4 thrombocytopenia. Monitor for hemorrhage and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Fluid Retention: Fatal and serious fluid retention events have occurred in patients who received ICLUSIG. In PACE, one instance of brain edema was fatal and serious events included pleural effusion, pericardial effusion, and angioedema. Monitor for fluid retention and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Cardiac Arrhythmias: Cardiac arrhythmias, including ventricular and atrial arrhythmias, occurred in patients in OPTIC and PACE. For some patients, events were serious or severe (Grade 3 or 4) and led to hospitalization. Monitor for signs and symptoms suggestive of slow heart rate (fainting, dizziness) or rapid heart rate (chest pain, palpitations or dizziness) and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Myelosuppression: Grade 3 or 4 events of neutropenia, thrombocytopenia, and anemia occurred in patients in OPTIC and PACE. The incidence of myelosuppression was greater in patients with AP-CML, BP-CML, and Ph+ ALL than in patients with CP-CML. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated. If ANC less than 1 x 109/L or platelets less than 50 x 109/L, interrupt ICLUSIG until ANC at least 1.5 x 109/L and platelets at least 75 x 109/L, then resume at same or reduced dose.

Tumor Lysis Syndrome (TLS): Serious TLS was reported in ICLUSIG-treated patients in OPTIC and PACE. Ensure adequate hydration and treat high uric acid levels prior to initiating ICLUSIG.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS (also known as Posterior Reversible Encephalopathy Syndrome) has been reported in patients who received ICLUSIG. Patients may present with neurological signs and symptoms, visual disturbances, and hypertension. Diagnosis is made with supportive findings on magnetic resonance imaging (MRI) of the brain. Interrupt ICLUSIG until resolution. The safety of resumption of ICLUSIG in patients upon resolution of RPLS is unknown.

Impaired Wound Healing and Gastrointestinal Perforation: Impaired wound healing occurred in patients receiving ICLUSIG. Withhold ICLUSIG for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of ICLUSIG after resolution of wound healing complications has not been established. Gastrointestinal perforation or fistula occurred in patients receiving ICLUSIG. Permanently discontinue in patients with gastrointestinal perforation.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal studies, ICLUSIG can cause fetal harm when administered to a pregnant woman Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ICLUSIG and for 3 weeks after the last dose.

ADVERSE REACTIONS
The most common (>20%) adverse reactions are rash and related conditions, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/lipase elevation, hemorrhage, anemia, hepatic dysfunction and AOEs. The most common Grade 3 or 4 laboratory abnormalities (>20%) are platelet count decreased, neutrophil cell count decreased, and white blood cell decreased.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-817-6468 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS
Strong CYP3A Inhibitors: Avoid coadministration or reduce ICLUSIG dose if coadministration cannot be avoided.
Strong CYP3A Inducers: Avoid coadministration.

USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed during treatment with ICLUSIG and for 6 days following last dose

Females and Males of Reproductive Potential: Verify pregnancy status of females of reproductive potential prior to initiating ICLUSIG.
Ponatinib may impair fertility in females, and it is not known if these effects are reversible.

Pre-existing Hepatic Impairment: Reduce the starting dose of ICLUSIG to 30mg orally once daily for patients with pre-existing hepatic impairment as these patients are more likely to experience adverse reactions compared to patients with normal hepatic function.

On December 9, 2022 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported the pricing of an underwritten offering of 15,384,616 shares of its common stock at a price of $6.50 per share (Press release, Erasca, DEC 9, 2022, View Source [SID1234639372]). All of the shares to be sold in the offering are to be sold by Erasca. The gross proceeds to Erasca from the offering, before deducting the underwriting discounts and commissions and other offering expenses, are expected to be approximately $100 million. The offering is expected to close on December 13, 2022, subject to the satisfaction of customary closing conditions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Erasca intends to use the net proceeds from this offering, together with its existing cash, cash equivalents and marketable securities, to fund the research and development of its product candidates and other development programs and for working capital and other general corporate purposes.

J.P. Morgan and Goldman Sachs & Co. LLC are acting as joint book-running managers for the offering.

The securities described above are being offered by Erasca pursuant to a shelf registration statement on Form S-3, including a base prospectus, that was previously filed with the Securities and Exchange Commission (SEC) and was declared effective on August 18, 2022. A prospectus supplement and accompanying prospectus relating to this offering will be filed with the SEC. When available, copies of the prospectus supplement and the accompanying prospectus relating to this offering may be obtained from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at (866) 803-9204, or by email at [email protected], or from Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526, or by email at [email protected]. Electronic copies of the prospectus supplement and accompanying prospectus will also be available on the website of the SEC at View Source

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.