First results from AMPLIFY trial will reinforce CALQUENCE^® as leading second-generation BTK inhibitor in frontline chronic lymphocytic leukemia with fixed-duration regimen

Next generation cell therapy and T-cell engagers will demonstrate promising early results in multiple types of blood cancer

New, long-term data for VOYDEYA™ as add-on to ULTOMIRIS^® or SOLIRIS^® will show low rate of breakthrough hemolysis events and sustained improvements in quality-of-life measures in PNH with extravascular hemolysis

AstraZeneca advances its ambition to redefine cancer care with new data across its industry-leading and diverse pipeline in hematology at the 66^th American Society of Hematology (ASH) Annual Meeting and Exposition December 7-10, 2024.

A total of 57 abstracts will feature 13 approved and potential new medicines from across AstraZeneca’s portfolio and pipeline in hematology, including from Alexion, its rare disease group, with data in key settings including chronic lymphocytic leukemia (CLL), multiple myeloma (MM), paroxysmal nocturnal hemoglobinuria (PNH) and other hematologic diseases.

Anas Younes, Senior Vice President, Hematology R&D, AstraZeneca, said: “Our data at ASH from the AMPLIFY Phase III trial will demonstrate the efficacy and safety of our leading second-generation BTK inhibitor, CALQUENCE^®, as a fixed-duration therapy in first-line CLL. In addition, new results for our novel T-cell engager, AZD0486, will reinforce its promising clinical profile in lymphomas, and data for our novel CAR T cell therapy, AZD0120, will highlight the potential of this therapy to transform treatment in multiple myeloma.”

Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: “Our ASH presentations will highlight the transformative impact of our medicines, including new analyses from the ALPHA Phase III trial reaffirming the safety and efficacy of our first-in-class Factor D inhibitor, VOYDEYA™ as add-on to ULTOMIRIS^® or SOLIRIS^® for the subset of patients with PNH experiencing clinically significant extravascular hemolysis. Further, new insights from our robust pipeline will enhance the understanding of several rare hematologic and cardiovascular conditions, underscoring our commitment to innovation in rare disease.”

CALQUENCE combinations demonstrate significant benefits across CLL and MCL

An oral presentation on interim results from the pivotal AMPLIFY Phase III trial will demonstrate the potential of fixed-duration CALQUENCE in combination with venetoclax, with or without obinutuzumab, in previously untreated adults with CLL compared to standard-of-care chemoimmunotherapy.¹ These results will be featured during the ASH Press Briefing on Sunday, December 9.

An updated analysis from the pivotal ECHO Phase III trial will further highlight the use of CALQUENCE in combination with bendamustine and rituximab as a first-line treatment option by demonstrating high and durable undetectable minimal residual disease (MRD) rates in previously untreated patients with mantle cell lymphoma (MCL) as well as showing the benefit of CALQUENCE across all patients including those with high-risk disease characteristics.² Results from ECHO were first presented as a late-breaking oral presentation at the European Hematology Association (EHA) 2024 Hybrid Congress in June.³

Results will also be shared from the ChangE Phase III trial, evaluating CALQUENCE compared with chlorambucil plus rituximab in first-line CLL in patients in China.⁴

New data show promise of next generation T-cell engagers and chimeric antigen receptor T-cell (CAR T) therapy

Two oral presentations will share results for the novel CD19xCD3 bispecific T-cell engager AZD0486, reinforcing the potential of this novel medicine as a new treatment option for B-cell malignancies.^5-6 Phase I results demonstrate high response rates, with a 96% overall response rate, 85% complete response rate and high rates of undetectable MRD in patients with relapsed/refractory follicular lymphoma (R/R FL) at doses of 2.4 mg and above.⁵ Additionally, interim Phase I results will show the early potential of AZD0486 in patients with heavily pretreated diffuse large B-cell lymphoma (DLBCL).⁶ Data will also reinforce the safety profile of AZD0486, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events effectively mitigated by the double step-up dosing schedule.⁷

Early data for AZD0120 (GC012F), a novel BCMAxCD19 dual-targeting autologous CAR T developed using the Gracell FasTCAR rapid manufacturing process, will show potential as a first-line therapy for elderly patients with newly diagnosed transplant ineligible MM.⁸ Preliminary results from the ongoing investigator-initiated trial of AZD0120 suggest deep responses and an acceptable safety profile, with no ICANS and no ≥Grade 2 CRS events observed in this patient population.⁸

An oral presentation will share preclinical data demonstrating the anti-tumor activity of AZD5492, a next-generation CD8 selective, CD20-targeting T-cell engager, designed using AstraZeneca’s innovative Target Induced T-cell Activating Nanobody (TITAN) platform. AZD5492 is currently being evaluated in Phase I clinical trials in R/R Non-Hodgkin lymphoma (NHL) and CLL.⁹

VOYDEYA (danicopan) as add-on to ULTOMIRIS (ravulizumab-cwvz) or SOLIRIS (eculizumab) demonstrates low rate of mild or moderate BTH events and improves quality-of-life measures in patients with PNH and clinically significant EVH

Data will be presented detailing events of breakthrough hemolysis (BTH), a key indicator of intravascular hemolysis and PNH disease control, reported in the ALPHA trial evaluating VOYDEYA as add-on to ULTOMIRIS or SOLIRIS in patients with PNH experiencing clinically significant extravascular hemolysis (EVH) and separately in the PEGASUS Phase III trial evaluating pegcetacoplan in patients with PNH previously treated with SOLIRIS. Data will show that 5/84 patients (6.0%) in the ALPHA trial and 19/80 patients (23.8%) in the PEGASUS trial experienced one or more BTH events. Moreover, most BTH events (6/7 or 85.7%) in the ALPHA trial were either mild or moderate, and all events were resolved without transfusion, dose modification or treatment withdrawal.¹⁰

Separately, final long-term patient-reported outcomes from the ALPHA trial will demonstrate VOYDEYA as add-on to ULTOMIRIS or SOLIRIS resulted in sustained improvements in fatigue, quality-of-life and physical function for up to 72 weeks in the subset of patients with PNH who experience clinically significant EVH.¹¹

Advancing understanding of life-threatening rare diseases

A US, retrospective chart review will provide real-world evidence showing hematologic and renal improvements in adults with atypical hemolytic uremic syndrome (aHUS) who switched to ULTOMIRIS after short-term use of SOLIRIS, with early responses and continued improvements through one year of treatment with ULTOMIRIS.¹²

Additionally, two presentations on amyloid light chain (AL) amyloidosis will highlight unmet medical needs in this progressive, debilitating disease, reinforcing the importance of bringing forward novel therapies to improve cardiovascular outcomes and organ function.^13-14

Key presentations during the 66^th ASH Annual Meeting and Exposition

INDICATIONS AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CALQUENCE is also indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE^® (acalabrutinib) tablets

Serious and Opportunistic Infections

Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding.

Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies

Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.9% of patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including CALQUENCE.

Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) of any grade in patients with relapsed or refractory MCL were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%).

*Treatment-emergent decreases (all grades) of hemoglobin (46%), platelets (44%), and neutrophils (36%) were based on laboratory measurements and adverse reactions.

Dose reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively. Increases in creatinine to 1.5 to 3 times the upper limit of normal (ULN) occurred in 4.8% of patients.

The most common adverse reactions (≥30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.

*Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions.

In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).

Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine to 1.5 to 3 times ULN occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.

In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in >5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection.

Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dose interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.

Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.

SPECIFIC POPULATIONS

Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.

Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for 1 week following the last dose of CALQUENCE.

It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for 2 weeks after the last dose.

Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Please see full Prescribing Information, including Patient Information.

INDICATION & IMPORTANT SAFETY INFORMATION FOR VOYDEYA^TM (danicopan)

INDICATION

What is VOYDEYA?

VOYDEYA is a prescription medicine used along with ravulizumab or eculizumab to treat breakdown of red blood cells that takes place outside of blood vessels (extravascular hemolysis), in adults with paroxysmal nocturnal hemoglobinuria (PNH).

It is not known if VOYDEYA is safe and effective in children.

IMPORTANT SAFETY INFORMATION

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

VOYDEYA is a medicine that affects your immune system. VOYDEYA may lower the ability of your immune system to fight infections.

• VOYDEYA increases your chance of getting serious infections caused by encapsulated bacteria. These serious infections may quickly become life-threatening and cause death if not recognized and treated early.

1. You must complete or update meningococcal vaccine(s) and streptococcus vaccine(s) at least 2 weeks before your first dose of VOYDEYA.
2. If you have not completed your vaccinations and VOYDEYA must be started right away, you should receive the required vaccinations as soon as possible.
3. If you have not been vaccinated at least 2 weeks before your first VOYDEYA dose and VOYDEYA must be started right away, you should also receive antibiotics to take for as long as your healthcare provider tells you.
4. If you have been vaccinated against these bacteria in the past, you might need additional vaccinations before starting VOYDEYA. Your healthcare provider will decide if you need additional vaccinations.
5. Vaccines do not prevent all infections caused by encapsulated bacteria. Call your healthcare provider or get emergency medical care right away if you have any of these signs and symptoms of a serious infection: fever with or without chills, fever and a rash, fever with chest pain and cough, fever with breathlessness/fast breathing, fever with high heart rate, headache with nausea or vomiting, headache and a fever, headache with a stiff neck or stiff back, confusion, body aches with flu-like symptoms, clammy skin, eyes sensitive to light.

Your healthcare provider will give you a Patient Safety Card about the risk of serious infections. Carry it with you at all times during treatment and for 1 week after your last VOYDEYA dose. Your risk of serious infections may continue for a few days after your last dose of VOYDEYA. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly.

VOYDEYA is only available through a program called the VOYDEYA Risk Evaluation and Mitigation Strategy (REMS). Before you can take VOYDEYA, your healthcare provider must: enroll in the VOYDEYA REMS; counsel you about the risk of serious infections caused by certain bacteria; give you information about the symptoms of serious infections; make sure that you are vaccinated against serious infections caused by encapsulated bacteria and that you receive antibiotics if you need to start VOYDEYA right away and you are not up to date on your vaccinations; give you a Patient Safety Card about your risk of serious infections, as discussed above.

Who should not receive VOYDEYA?

Do not take VOYDEYA if you have a serious infection caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae type B infection.

Before taking VOYDEYA, tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever, have liver problems, are pregnant or plan to become pregnant, or are breastfeeding. It is not known if VOYDEYA will harm your unborn baby or if it passes into your breast milk. Do not breastfeed during treatment with VOYDEYA and for 3 days after the last dose.

Tell your healthcare provider about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment. VOYDEYA may affect the way other medicines work.

If you stop taking VOYDEYA, your healthcare provider will need to monitor you closely for at least 2 weeks after your last dose. Stopping treatment with VOYDEYA may cause a breakdown of red blood cells due to PNH. Symptoms or problems that can happen due to breakdown of red blood cells include: decreased hemoglobin level in your blood and tiredness

What are the possible side effects of VOYDEYA?

VOYDEYA can cause serious side effects, including increased liver enzyme levels and increased cholesterol. Your healthcare provider will do blood tests to check your liver enzyme levels and cholesterol before and during treatment with VOYDEYA. Your healthcare provider may temporarily or permanently stop treatment with VOYDEYA if you develop increased liver enzyme levels.

The most common side effect of VOYDEYA is headache.

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all of the possible side effects of VOYDEYA. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see the accompanying full Prescribing Information and Medication Guide for VOYDEYA (danicopan), including Boxed WARNING regarding serious infections caused by encapsulated bacteria.

INDICATION(S) & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS ^® (ravulizumab-cwvz)

INDICATION(S)

What is ULTOMIRIS?

ULTOMIRIS is a prescription medicine used to treat:

• adults and children 1 month of age and older with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH).
• adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
• adults with a disease called generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.
• adults with a disease called Neuromyelitis Optica Spectrum Disorder (NMOSD) who are anti-aquaporin 4 (AQP4) antibody positive.

It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age.

It is not known if ULTOMIRIS is safe and effective for the treatment of gMG or NMOSD in children.

IMPORTANT SAFETY INFORMATION

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

ULTOMIRIS is a medicine that affects your immune system and may lower the ability of your immune system to fight infections.

• ULTOMIRIS increases your chance of getting serious meningococcal infections that may quickly become life-threatening or cause death if not recognized and treated early.

1. You must complete or update meningococcal vaccine(s) at least 2 weeks before your first dose of ULTOMIRIS.
2. If you have not completed your meningococcal vaccines and ULTOMIRIS must be started right away, you should receive the required vaccine(s) as soon as possible.
3. If you have not been vaccinated and ULTOMIRIS must be started right away, you should also receive antibiotics for as long as your healthcare provider tells you.
4. If you had a meningococcal vaccine in the past, you might need additional vaccines before starting ULTOMIRIS. Your healthcare provider will decide if you need additional meningococcal vaccines.
5. Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: fever, fever with high heart rate, headache and fever, confusion, muscle aches with flu-like symptoms, fever and a rash, headache with nausea or vomiting, headache with a stiff neck or stiff back, or eyes sensitive to light.

Your healthcare provider will give you a Patient Safety Card about the risk of serious meningococcal infection. Carry it with you at all times during treatment and for 8 months after your last ULTOMIRIS dose. Your risk of meningococcal infection may continue for several months after your last dose of ULTOMIRIS. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly.

ULTOMIRIS is only available through a program called the ULTOMIRIS and SOLIRIS Risk Evaluation and Mitigation Strategy (REMS). Before you can receive ULTOMIRIS, your healthcare provider must: enroll in the REMS program; counsel you about the risk of serious meningococcal infections; give you information about the signs and symptoms of serious meningococcal infection; make sure that you are vaccinated against serious infections caused by meningococcal bacteria, and that you receive antibiotics if you need to start ULTOMIRIS right away and are not up to date on your vaccines; give you a Patient Safety Card about your risk of meningococcal infection.

ULTOMIRIS may also increase the risk of other types of serious infections, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. Your child should receive vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) if treated with ULTOMIRIS. Certain people may be at risk of serious infections with gonorrhea.

Who should not receive ULTOMIRIS?

Do not receive ULTOMIRIS if you have a serious meningococcal infection when you are starting ULTOMIRIS.

Before you receive ULTOMIRIS, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection or fever
• are pregnant or plan to become pregnant. It is not known if ULTOMIRIS will harm your unborn baby.
  • Pregnancy Registry: There is a registry for pregnant women who take ULTOMIRIS to check the health of the pregnant mother and her baby. If you are pregnant or become pregnant while taking ULTOMIRIS, talk to your healthcare provider about how you can join this registry or you may contact the registry at 1-833-793-0563 or www.UltomirisPregnancyStudy.com to enroll.
• are breastfeeding or plan to breastfeed. It is not known if ULTOMIRIS passes into your breast milk. You should not breastfeed during treatment and for 8 months after your final dose of ULTOMIRIS.

Tell your healthcare provider about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment.

If you have PNH and you stop receiving ULTOMIRIS, your healthcare provider will need to monitor you closely for at least 16 weeks after you stop ULTOMIRIS. Stopping ULTOMIRIS may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in your red blood cell count, tiredness, blood in your urine, stomach-area (abdomen) pain, shortness of breath, blood clots, trouble swallowing, and erectile dysfunction (ED) in males.

If you have aHUS, your healthcare provider will need to monitor you closely for at least 12 months after stopping treatment for signs of worsening aHUS or problems related to a type of abnormal clotting and breakdown of your red blood cells called thrombotic microangiopathy (TMA). Symptoms or problems that can happen with TMA may include: confusion or loss of consciousness, seizures, chest pain (angina), difficulty breathing and blood clots or stroke.

What are the possible side effects of ULTOMIRIS?

ULTOMIRIS can cause serious side effects including infusion-related reactions. Symptoms of an infusion-related reaction with ULTOMIRIS may include lower back pain, stomach (abdominal) pain, muscle spasms, changes in blood pressure, tiredness, feeling faint, shaking chills (rigors), discomfort in your arms or legs, or bad taste. Stop treatment of ULTOMIRIS and tell your healthcare provider right away if you develop these symptoms, or any other symptoms during your ULTOMIRIS infusion that may mean you are having a serious infusion-related reaction, including: chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out.

The most common side effects of ULTOMIRIS in people treated for PNH are upper respiratory tract infection and headache.

The most common side effects of ULTOMIRIS in people treated for aHUS are upper respiratory tract infection, diarrhea, nausea, vomiting, headache, high blood pressure and fever.

The most common side effects of ULTOMIRIS in people with gMG are diarrhea and upper respiratory tract infections.

The most common side effects of ULTOMIRIS in people with NMOSD are COVID-19 infection, headache, back pain, urinary tract infection, and joint pain (arthralgia).

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of ULTOMIRIS. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider right away if you miss an ULTOMIRIS infusion or for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see the accompanying full Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious meningococcal infections.

INDICATION(S) & IMPORTANT SAFETY INFORMATION FOR SOLIRIS^® (eculizumab)

INDICATION(S)

What is SOLIRIS?

SOLIRIS is a prescription medicine used to treat:

• people with paroxysmal nocturnal hemoglobinuria (PNH).
• people with atypical hemolytic uremic syndrome (aHUS).
  
  SOLIRIS is not for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
• adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.
• adults with a disease called neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.

It is not known if SOLIRIS is safe and effective in children with PNH, gMG, or NMOSD

IMPORTANT SAFETY INFORMATION

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

SOLIRIS is a medicine that affects your immune system and may lower the ability of your immune system to fight infections.

• SOLIRIS increases your chance of getting serious meningococcal infections that may quickly become life-threatening or cause death if not recognized and treated early.

1. You must complete or update your meningococcal vaccine(s)at least 2 weeks before your first dose of SOLIRIS.
2. If you have not been vaccinated and SOLIRIS must be started right away, you should receive the required vaccine(s) as soon as possible.
3. If you have not been vaccinated and SOLIRIS must be started right away, you should also receive antibiotics for as long as your healthcare provider tells you.
4. If you had a meningococcal vaccine in the past, you might need additional vaccines before starting SOLIRIS. Your healthcare provider will decide if you need additional meningococcal vaccines.
5. Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a serious meningococcal infection: fever, fever with high heart rate, headache and fever, confusion, muscle aches with flu-like symptoms, fever and rash, headache with nausea or vomiting, headache with a stiff neck or stiff back, or eyes sensitive to light.

Your healthcare provider will give you a Patient Safety Card about the risk of serious meningococcal infection. Carry it with you at all times during treatment and for 3 months after your last dose of SOLIRIS. Your risk of meningococcal infection may continue for several weeks after your last dose of SOLIRIS. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly.

SOLIRIS is only available through a program called the ULTOMIRIS and SOLIRIS Risk Evaluation and Mitigation Strategy (REMS). Before you can receive SOLIRIS, your healthcare provider must: enroll in the REMS program; counsel you about the risk of serious meningococcal infections; give you information about the signs and symptoms of serious meningococcal infection; make sure that you are vaccinated against serious infections caused by meningococcal bacteria, and that you receive antibiotics if you need to start SOLIRIS right away and you are not up to date on your vaccines; give you a Patient Safety Card about your risk of meningococcal infection.

SOLIRIS may also increase the risk of other types of serious infections, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. Your child should receive vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) if treated with SOLIRIS. Certain people may be at risk of serious infections with gonorrhea. Certain fungal infections (Aspergillus) may occur if you take SOLIRIS and have a weak immune system or a low white blood cell count.

Who should not receive SOLIRIS?

Do not receive SOLIRIS if you have a serious meningococcal infection when you are starting SOLIRIS.

Before you receive SOLIRIS, tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed. It is not known if SOLIRIS will harm your unborn baby or if it passes into your breast milk.

Tell your healthcare provider about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment.

If you have PNH, your healthcare provider will need to monitor you closely for at least 8 weeks after stopping SOLIRIS. Stopping treatment with SOLIRIS may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in the number of your red blood cell count, drop in your platelet count, confusion, kidney problems, blood clots, difficulty breathing, and chest pain.

If you have aHUS, your healthcare provider will need to monitor you closely during and for at least 12 weeks after stopping SOLIRIS for signs of worsening aHUS symptoms or problems related to abnormal clotting (thrombotic microangiopathy). Symptoms or problems that can happen with abnormal clotting may include: stroke, confusion, seizure, chest pain (angina), difficulty breathing, kidney problems, swelling in arms or legs, and a drop in your platelet count.

What are the possible side effects of SOLIRIS?

SOLIRIS can cause serious side effects including serious infusion-related reactions. Tell your healthcare provider or nurse right away if you get any of these symptoms during your SOLIRIS infusion: chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out. If you have an infusion-related reaction to SOLIRIS, your healthcare provider may need to infuse SOLIRIS more slowly, or stop SOLIRIS.

The most common side effects in people with PNH treated with SOLIRIS include: headache, pain or swelling of your nose or throat (nasopharyngitis), back pain, and nausea.

The most common side effects in people with aHUS treated with SOLIRIS include: headache, diarrhea, high blood pressure (hypertension), common cold (upper respiratory infection), stomach-area (abdominal) pain, vomiting, pain or swelling of your nose or throat (nasopharyngitis), low red blood cell count (anemia), cough, swelling of legs or feet (peripheral edema), nausea, urinary tract infections, and fever.

The most common side effects in people with gMG treated with SOLIRIS include: muscle and joint (musculoskeletal) pain.

The most common side effects in people with NMOSD treated with SOLIRIS include: common cold (upper respiratory infection), pain or swelling of your nose or throat (nasopharyngitis), diarrhea, back pain, dizziness, flu like symptoms (influenza) including fever, headache, tiredness, cough, sore throat, and body aches, joint pain (arthralgia), throat irritation (pharyngitis), and bruising (contusion).

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of SOLIRIS. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious meningococcal infections

Notes

CALQUENCE^® (acalabrutinib)

CALQUENCE^® (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity.¹⁵ In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

CALQUENCE has been used to treat more than 85,000 patients worldwide¹⁶ and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. CALQUENCE is also approved in the US, China and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. CALQUENCE is not currently approved for the treatment of MCL in Japan or the EU.

As part of an extensive clinical development program, CALQUENCE is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

VOYDEYA™ (danicopan)

VOYDEYA™ (danicopan) is a first-in-class oral Factor D inhibitor. The medication works by selectively inhibiting Factor D, a complement system protein that plays a key role in the amplification of the complement system response. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. VOYDEYA has been granted Breakthrough Therapy designation by the US Food and Drug Administration and PRIority MEdicines (PRIME) status by the European Medicines Agency. VOYDEYA has also been granted Orphan Drug Designation in the US, EU and Japan for the treatment of PNH.

VOYDEYA is approved in the US, EU, Japan and other countries as add-on therapy to ravulizumab or eculizumab for the treatment of certain adults with PNH.

Alexion is also evaluating VOYDEYA as a potential monotherapy for geographic atrophy in a Phase II clinical trial.

ULTOMIRIS^® (ravulizumab-cwvz)

ULTOMIRIS^® (ravulizumab-cwvz), the longest-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Following a loading dose, ULTOMIRIS is administered intravenously every eight weeks in adults, or every four or eight weeks in pediatric patients (based on body weight).

ULTOMIRIS is approved in the US, EU, Japan and other countries for the treatment of certain adults with paroxysmal nocturnal hemoglobinuria (PNH) and for certain children with PNH in the US and EU.

ULTOMIRIS is also approved in the US, EU, Japan and other countries for the treatment of certain adults and children with atypical hemolytic uremic syndrome (aHUS).

Additionally, ULTOMIRIS is approved in the US, EU, Japan and other countries for the treatment of certain adults with generalized myasthenia gravis (gMG).

Further, ULTOMIRIS is approved in the US, EU, Japan and other countries for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

ULTOMIRIS is being assessed as a treatment for additional indications as part of a broad development program.

SOLIRIS^® (eculizumab)

SOLIRIS^® (eculizumab) is a first-in-class C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the terminal complement cascade over-responds, leading the body to attack its own healthy cells. SOLIRIS is administered intravenously every two weeks, following an introductory dosing period.

SOLIRIS is approved in the US, EU, Japan, China and other countries for the treatment of certain children and adults with paroxysmal nocturnal hemoglobinuria (PNH).

SOLIRIS is also approved in the US, EU, Japan, China and other countries for the treatment of certain children and adults with atypical hemolytic uremic syndrome (aHUS).

Additionally, SOLIRIS is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with generalized myasthenia gravis (gMG), and for certain pediatric patients with gMG in the EU, Japan and other countries.

Further, SOLIRIS is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

SOLIRIS is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome.

AstraZeneca in hematology

AstraZeneca is pushing the boundaries of science to redefine care in hematology. Our goal is to help transform the lives of patients living with malignant, rare and other related hematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians.

In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our hematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies.

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

Alexion

Alexion, AstraZeneca Rare Disease is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.

References

1. Brown, J et al. Fixed-Duration Acalabrutinib plus Venetoclax with or without Obinutuzumab versus Chemoimmunotherapy for First-Line Treatment of Chronic Lymphocytic Leukemia: Interim Analysis of the Multicenter, Open-label, Randomized, Phase 3 AMPLIFY Trial. Presented at ASH 2024. Abstract 1009. 2024.
2. Dreyling, M et al. High-risk Subgroups and MRD: An Updated Analysis of the Phase 3 ECHO Trial of Acalabrutinib with Bendamustine/Rituximab in Previously Untreated Mantle Cell Lymphoma. Presented at ASH 2024. Abstract 1626. 2024.
3. Wang, M et al. Acalabrutinib plus bendamustine and rituximab in untreated mantle cell lymphoma: Results from the Phase 3, Double-Blind, Placebo-Controlled ECHO Trial. Presented at EHA 2024. Abstract LBA3439. 2024
4. Qiu, L et al. Acalabrutinib Versus Chlorambucil Plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia: A Randomized, Multicenter, Open Label, Phase 3 Study. Presented at ASH 2024. Abstract 3251. 2024.
5. Gaballa, S et al. Evaluation of AZD0486, a Novel CD19xCD3 T-Cell Engager, in Relapsed/Refractory Diffuse Large B-cell Lymphoma in an Ongoing First-in-Human Phase 1 Study: High Complete Responses Seen in CAR-T–naive and CAR-T–exposed Patients. Presented at ASH 2024. Abstract 868. 2024.
6. Hou, J et al. Escalating Doses of AZD0486, a Novel CD19xCD3 T-cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma. Presented at ASH 2024. Abstract 341. 2024.
7. Zhu, X et al. Exposure-Response analysis and Quantitative Systems Pharmacology modelling for an optimal dose selection of AZD0486 in follicular lymphoma patients. Presented at ASH 2024. Abstract 2794. 2024.
8. Du, J et al. A phase I study of dual targeting BCMA and CD19 FasTCAR-T cells (GC012F) as first-line therapy for transplant-ineligible newly diagnosed multiple myeloma. Presented at ASH 2024. Abstract 2072. 2024.
9. Lawrence, R et al. Pre-Clinical Evaluation of AZD5492, a Novel CD8-Guided T Cell Engager, for B-Non-Hodgkin Lymphoma Indications. Presented at ASH 2024. Abstract 959. 2024.
10. Schrezenmeier H, Mahdi M, Gasteyger C, et al. Breakthrough Hemolysis Events in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from Danicopan and Pegcetacoplan Trials. Presented at ASH 2024. Abstract 2694. 2024.
11. Piatek C, Lee JW, Griffin M, et al. Danicopan as Add-On Therapy to Ravulizumab or Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Patient-Reported Outcomes from the Phase 3 ALPHA Trial. Presented at ASH 2024. Abstract 2692. 2024.
12. Chaturvedi S, Wang Y, Ong M-L, et al. Real-World Effectiveness of Ravulizumab Among Adults with Atypical Hemolytic Uremic Syndrome (aHUS) who Switched to Ravulizumab Within 3 Months of Eculizumab Treatment: A Physician Panel-Based Chart Review Study (aHUS IMPACT). Presented at ASH 2024. Abstract 2613. 2024.
13. Laires P, Thompson J, Catini J, et al. Comparison of Alternative Mayo Staging Classification Systems Used in Light-Chain Amyloidosis. Presented at ASH 2024. Abstract 6887. 2024.
14. Thompson J, Catini J, Ouyang D, et al. Evaluation of Functional Cardiac Measures and Response to Treatment Initiation in Patients with Systemic Light-Chain (AL) Amyloidosis: Results from a Single Site Retrospective Study. Presented at ASH 2024. Abstract 4677. 2024.
15. Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21). doi:10.1186/s13045-016-0250-9.
16. Data on File, REF-236261. AstraZeneca Pharmaceuticals LP.

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