OXBRYTA® (voxelotor) 14 CLINICAL STUDIES

(voxelotor)

Prescribing Information

14 CLINICAL STUDIES

14.1 Adults and Pediatric Patients 12 Years and Older

The efficacy and safety of OXBRYTA in SCD was evaluated in HOPE, a Phase 3 randomized, double-blind, placebo-controlled, multicenter trial [NCT 03036813]. In this study, 274 patients were randomized to daily oral administration of OXBRYTA 1,500 mg (N=90), OXBRYTA 900 mg (N=92), or placebo (N=92). Patients were included if they had from 1 to 10 vasoocclusive crisis (VOC) events within 12 months prior to enrollment and baseline hemoglobin (Hb) ≥5.5 to ≤10.5 g/dL. Eligible patients on stable doses of hydroxyurea for at least 90 days were allowed to continue hydroxyurea therapy throughout the study. Randomization was stratified by patients already receiving hydroxyurea (yes, no), geographic region (North America, Europe, Other), and age (12 to <17 years, 18 to 65 years). The trial excluded patients who received red blood cell (RBC) transfusions within 60 days and erythropoietin within 28 days of enrollment, had renal insufficiency, uncontrolled liver disease, were pregnant, or lactating.

The majority of patients had HbSS or HbS/beta0-thalassemia genotype (90%) and were receiving background hydroxyurea therapy (65%). The median age was 24 years (range: 12 to 64 years); 46 (17%) patients were 12 to <17 years. Median baseline Hb was 8.5 g/dL (5.9 to 10.8 g/dL). One hundred and fifteen (42%) had 1 VOC event and 159 (58%) had 2 to 10 events within 12 months prior to enrollment. In the OXBRYTA 1,500 mg group, 63 (70%) patients completed the study through Week 72.

Efficacy was based on Hb response rate defined as a Hb increase of >1 g/dL from baseline to Week 24 in patients treated with OXBRYTA 1,500 mg versus placebo. The response rate for OXBRYTA 1,500 mg was 51.1% (46/90) compared to 6.5% (6/92) in the placebo group (p < 0.001). No outlier subgroups were observed. The distribution of Hb change from baseline for individual patients completing 24 weeks of treatment with OXBRYTA 1,500 mg or placebo is depicted in Figure 1.

*: Approximately 83% of all randomized patients completed 24 weeks of treatment.

Figure 1: Subject-level Change from Baseline in Hemoglobin at Week 24 in Patients Who Completed 24 Weeks of Treatment*

Additional efficacy evaluation included change in Hb and percent change in indirect bilirubin and percent reticulocyte count from baseline to Week 24 (Table 6).

Table 6: Adjusted Mean (SE) Change from Baseline to Week 24 in Hemoglobin and Clinical Measures of Hemolysis
	OXBRYTA 1,500 mg QD (N=90)	Placebo (N=92)	P Value
QD = once daily; SE = standard error
Hemoglobin	1.1 g/dL (0.1)	-0.1 g/dL (0.1)	< 0.001
Indirect Bilirubin	-29.1% (3.5)	-2.8% (3.5)	< 0.001
Percent Reticulocyte Count	-18.0% (4.7)	6.8% (4.7)	< 0.001

14.2 Pediatric Patients 4 to <12 Years

The efficacy and safety of OXBRYTA in patients 4 to <12 years with SCD was evaluated in an open-label, multi-center, Phase 2 trial [NCT 02850406]. In this study, 45 patients 4 to <12 years and 11 patients 12 to <17 years received OXBRYTA. Patients 4 to <12 years received tablets for oral suspension based on body weight at baseline. OXBRYTA doses of 600 mg, 900 mg, or 1,500 mg once daily were administered to patients weighing 10 kg to <20 kg, 20 kg to <40 kg, or ≥40 kg, respectively. Patients 12 to <17 years received OXBRYTA 1,500 mg once daily.

Patients were included if their baseline hemoglobin (Hb) was ≤10.5 g/dL. Eligible patients on stable doses of hydroxyurea for at least 90 days were allowed to continue hydroxyurea therapy throughout the study. The trial excluded patients who had a VOC event within 14 days prior to enrollment, received red blood cell (RBC) transfusions within 30 days of enrollment, and had renal insufficiency or uncontrolled liver disease.

All patients had HbSS or HbS/beta0-thalassemia genotype (100%) and most were receiving background hydroxyurea therapy (80%). The median age was 8 years (range: 4 to 15 years); 45 (80%) patients were 4 to <12 years. In this age group, mean baseline Hb was 8.6 g/dL (range: 6.1 to 10.5 g/dL).

Efficacy was based on Hb response rate, which is defined as a Hb increase of >1 g/dL from baseline to Week 24. Hb response rate for OXBRYTA in patients aged 4 to <12 years who took at least one dose of OXBRYTA was 36% (16/45) (95% CI: 21.6%, 49.5%).

Medication Guide

MEDICATION GUIDE

This Patient Information has been approved by the U.S. Food and Drug Administration				Revised: 08/2023
PATIENT INFORMATION
	OXBRYTA® (ox brye ta) (voxelotor) tablets			OXBRYTA® (ox brye ta) (voxelotor) tablets for oral suspension
What is OXBRYTA? OXBRYTA is a prescription medicine used for the treatment of sickle cell disease in adults and children 4 years of age and older. It is not known if OXBRYTA is safe and effective in children with sickle cell disease below 4 years of age.
Do not take OXBRYTA if you or your child have had an allergic reaction to voxelotor or any of the ingredients in OXBRYTA. See the end of this leaflet for a list of the ingredients in OXBRYTA.
Before taking OXBRYTA, tell your healthcare provider about all of your medical conditions, including if you or your child: • have liver problems • are pregnant or plan to become pregnant. It is not known if OXBRYTA can harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if OXBRYTA can pass into your breastmilk and if it can harm your baby. Do not breastfeed during treatment with OXBRYTA and for at least 2 weeks after the last dose. Tell your healthcare provider about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how OXBRYTA works. OXBRYTA may also affect how other medicines work and may affect the results of certain blood tests. Keep a list of all your medicines and show it to your healthcare provider.
How should I take OXBRYTA? • Take OXBRYTA exactly as your healthcare provider tells you. • Do not change your dose or stop taking OXBRYTA unless your healthcare provider tells you to. Your healthcare provider may change your dose if needed. • Take your prescribed dose of OXBRYTA 1 time each day. • Take OXBRYTA with or without food. • OXBRYTA comes in two different dosage forms, OXBRYTA tablets and OXBRYTA tablets for oral suspension. Your healthcare provider will decide which dosage form you take based on your age, weight, and ability to swallow tablets. o If you take OXBRYTA tablets: Swallow each OXBRYTA tablet whole. Do not cut, crush, or chew the tablets. o If you take OXBRYTA tablets for oral suspension: See the detailed Instructions for Use on how to prepare and take your dose. You must mix the OXBRYTA tablets for oral suspension in room temperature clear drink, such as drinking water, clear soda, apple juice, clear electrolyte drinks, clear flavored drinks, or clear sports drinks, right before taking it. Do not swallow whole, cut, crush, or chew the tablets for oral suspension. • Check to make sure you receive the correct dosage form of OXBRYTA each time your prescription is filled to avoid taking the wrong medicine. • Your healthcare provider may also prescribe a medicine called hydroxyurea during treatment with OXBRYTA. • If you or your child miss a dose of OXBRYTA or if the entire dose is not taken, skip that dose and return to your normal dosing schedule the next day.
What should I avoid while taking OXBRYTA? Do not take St. John's wort during treatment with OXBRYTA.
What are the possible side effects of OXBRYTA? OXBRYTA can cause serious side effects, including: • Severe skin rash and serious allergic reactions. Treatment with OXBRYTA may cause severe skin reactions and serious allergic reactions. The organs in your body may also be affected, such as your liver, kidneys or lungs, and your blood cells. • Stop taking OXBRYTA, and tell your healthcare provider or get emergency medical help right away if you develop any of the following signs or symptoms during treatment:
	o rash o hives o high temperature (fever) o swollen glands (lymph nodes) o trouble swallowing		o shortness of breath (difficult breathing) o swelling of your face, around your eyes, lips, or tongue o lack of energy and tiredness (fatigue) o muscle or joint aches
The most common side effects of OXBRYTA include:
• headache • diarrhea • stomach-area (abdominal) pain		• nausea • rash or hives • fever
The most common side effects of OXBRYTA in children ages 4 to less than 12 years of age include:
• fever • vomiting • rash		• stomach-area (abdominal) pain • diarrhea • headache
These are not all the possible side effects of OXBRYTA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Pfizer Inc. at 1-800-438-1985.
How should I store OXBRYTA? • Store OXBRYTA between 68°F to 86°F (20°C to 30°C). • The OXBRYTA bottle comes with a child-resistant closure. • The OXBRYTA bottle may contain a desiccant canister to help keep your medicine dry (protect it from moisture) and a polyester coil. Do not eat the desiccant or polyester coil. Keep OXBRYTA and all medicines out of the reach of children.
General information about the safe and effective use of OXBRYTA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use OXBRYTA for a condition for which it was not prescribed. Do not give OXBRYTA 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 OXBRYTA that is written for health professionals.
What are the ingredients of OXBRYTA? Active Ingredient: voxelotor Inactive Ingredients: OXBRYTA tablets: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The 500 mg tablet film coating contains: polyethylene glycol 3350, polyvinyl alcohol, talc, titanium dioxide, and yellow iron oxide. The 300 mg tablet film coating contains: black and red iron oxide, polyethylene glycol 3350, polyvinyl alcohol, talc, and titanium dioxide. OXBRYTA tablets for oral suspension: artificial grape flavor, colloidal silicon dioxide, croscarmellose sodium, iron oxide pigment, magnesium stearate, microcrystalline cellulose, and sucralose. Distributed by Global Blood Therapeutics, Inc A subsidiary of Pfizer Inc. South San Francisco, CA 94080 LAB-1567-1.0 For more information, go to www.pfizer.com or call 1-800-438-1985.

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