Drug Trials Snapshots: OJJAARA

HOW TO USE THIS SNAPSHOT

The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT

Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the OJJAARA Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

OJJAARA (momelotinib) 
oh-JAR-uh
GlaxoSmithKline, LLC
Original Approval date: September 15, 2023

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DRUG TRIALS SNAPSHOT SUMMARY

What is the drug for?

OJJARA is a drug used to treat a rare type of bone marrow disorder called myelofibrosis (MF) in adults with anemia.

MF is a chronic disorder where scar tissue forms in the bone marrow, resulting in decreased production of blood cells in the bone marrow. In patients with MF, production of blood cells can then begin to occur in the spleen and liver, causing enlargement of these organs. Anemia in patients with MF is caused by decreased production of red blood cells (RBCs) in the bone marrow along with destruction of RBCs in the spleen.

How is this drug used?

OJJAARA is a tablet that is taken by mouth once daily.

Who participated in the clinical trials?

FDA approved OJJAARA based on evidence from two clinical trials (MOMENTUM and SIMPLIFY‑1) in patients with intermediate or high-risk MF, including primary MF or secondary MF (post-polycythemia vera and post-essential thrombocythemia) with anemia. The trials were conducted at 196 sites in 24 countries in Asia, Australia, Europe, and North America. The efficacy and safety of OJJAARA was assessed in both trials. A total of 375 participants out of 376 received at least one dose of OJJAARA, danazol or ruxolitinib.

How were the trials designed?

OJJAARA was evaluated in two clinical trials of 376 adult patients with intermediate or high-risk MF, including primary MF or secondary MF (post-polycythemia vera and post-essential thrombocythemia) with anemia.

MOMENTUM was a double-blind, randomized, active-controlled trial in 195 symptomatic and anemic adult patients with MF who had previously been treated with an approved Janus kinase (JAK) inhibitor agent. Patients were randomized 2:1 to receive OJJAARA 200 mg once daily (n=130) or danazol 300 mg twice daily (n=65). Patients received blinded treated for 24 weeks then switched to open-label treatment with OJJAARA. Randomization was stratified by baseline Myelofibrosis Symptom Assessment Form (MFSAF v4.0) Total Symptom Score (TSS; <22, ≥22), baseline palpable spleen length below the left costal margin (LCM; <12, ≥12 cm), baseline red blood cell (RBC) or whole blood units transfused in the 8 weeks before randomization (0, 1 to 4, ≥5 units), and trial site.

The primary efficacy outcome measure was TSS reduction of at least 50%, based on MFSAF v4.0 instrument, over the 28 days immediately before the end of Week 24, compared with baseline. MFSAF v4.0 is a patient reported outcome instrument that assesses the seven core symptoms of MF of fatigue (weariness and tiredness), night sweats (or feeling hot or flushed), itching, abdominal discomfort (feeling pressure or bloating), pain under ribs on left side, feeling of fullness after beginning to eat, and bone pain. Additional efficacy outcome measures were RBC transfusion independence (TI) and at least 25% reduction in spleen volume compared to baseline, as measure by magnetic resonance imaging (MRI) or computed tomography (CT).

The median age of patients enrolled was 71 years (range 38 to 86 years), with 79% aged 65 years and older. Sixty-three percent of patients were male. Eighty-one percent of patients were White, 9% Asian, 2% Black, and 6% Hispanic or Latino. Sixty-four percent of patients had primary MF, 19% had post-PV MF, and 17% had post-ET MF. Five percent of patients had intermediate-1 risk, 57% had intermediate-2 risk, 35% had high-risk disease, and 5% had unknown risk category.

At baseline, 13% and 15% of patients were transfusion independent (no RBC transfusions in the 12 weeks before the first dose and Hb ≥8 g/dL) in the OJJAARA and danazol groups, respectively. The baseline median Hb measurement was 8 g/dL, and the median platelet count was 96 × 109 /L (range 24 × 109 /L to 733 × 109 /L). The baseline median palpable spleen length was 11 cm below the left costal margin; the median central spleen volume measured by MRI/CT was 2,105 cm3 (range 609 cm3 to 9,717 cm3).

In MOMENTUM, after 24 weeks of therapy, OJJAARA was superior to danazol on reducing the total symptom score with 25% of patients who received OJJAARA having at least 50% reduction in TSS compared to 9% of patients who received danazol. In addition, a significantly higher percentage of patients treated with OJJAARA achieved transfusion independence between weeks 12 and 24 compared to patients treated with danazol (30% vs. 20%), and a significantly higher percentage of patients treated with OJJAARA had a reduction in spleen volume of at least 25% compared to patients treated with danazol (39% vs 6%).

SIMPLIFY-1 was a double-blind, randomized, active-controlled trial in 432 adults with MF who had not previously received a JAK inhibitor. Patients were randomized 1:1 to receive OJJAARA 200 mg once daily or ruxolitinib adjusted dose twice daily, for 24 weeks. There was a subgroup of patients enrolled in this study (n=181) who had anemia (hemoglobin <10 g/dL) at baseline.

The primary efficacy outcome measure was achievement of at least 35% reduction in spleen volume at Week 24 compared to baseline as measured by MRI or CT. Additional efficacy outcome measures were achieving at least 50% reduction in TSS from baseline, based on mMPN-SAF v2.0 instrument, at Week 24, and RBC transfusion independence.

How were the trials designed?  

The median age was 68 years (range 25 to 86 years), with 67% age 65 years and older; 59% of patients were male; 80% of patients were White; 8% Asian, 1% Black, and 2% Hispanic or Latino. Sixty-three percent of patients had primary MF, 13% had post-PV MF, and 24% had post-ET MF. Four percent of patients had intermediate-1 risk, 25% had intermediate-2 risk, and 71% had high-risk disease.

At baseline, 29% and 44% of patients were transfusion independent in the groups treated with OJJAARA or ruxolitinib, respectively. The baseline median Hb measurement was 8.8 g/dL, and the median platelet count was 193 × 109 /L (range 54 × 10 /L to 2,865 × 10 /L). Median palpable spleen length at baseline was 12 cm below the left costal margin; the median spleen volume at baseline (measured by MRI or CT) was 1,843 cm3 (range 352 cm3 to 9,022 cm3).

After 24 weeks of therapy, SIMPLIFY-1 demonstrated OJJAARA to be non-inferior to ruxolitinib treatment in reducing the spleen volume by ≥35%, which occurred in 27% of patients treated with OJJAARA compared to 30% of patients treated with ruxolitinib. Non-inferiority of OJJAARA compared to ruxolitinib in TSS reduction of at least 50% was not demonstrated, although 28% of patients who received OJJAARA did have a reduction of at last 50% in TSS score.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many males and females were enrolled across the clinical trials used to evaluate the efficacy and safety of OJJAARA.

Figure 1. Baseline Demographics by Sex

Source: Adapted from FDA Review

Figure 2 summarizes how many patients by race enrolled across the clinical trials used to evaluate the efficacy and the side effects of OJJAARA.

Figure 2. Baseline Demographics by Race

Source: Adapted from FDA Review

Figure 3 summarizes how many patients by age enrolled across the clinical trials used to evaluate the efficacy and the side effects of OJJAARA.

Figure 3. Baseline Demographics by Age

Source: Adapted from FDA Review

Figure 4 summarizes how many patients by ethnicity enrolled across the clinical trials used to evaluate the efficacy and the side effects of OJJAARA.

Figure 4. Baseline Demographics by Ethnicity

Source: Adapted from FDA Review

Who participated in the trials?

Table 1. Baseline Demographic Characteristics, ITT Population, MOMENTUM

Characteristic	OJJAARA N=130	Danazol N=65	Total N=195
Sex, n (%)
Female	51 (39)	21 (32)	72 (37)
Male	79 (61)	44 (68)	123 (63)
Age, years
Mean (SD)	69.8 (8.2)	71.5 (7)	70.4 (7.9)
Median (min, max)	71 (38, 86)	72 (54, 86)	71 (38, 86)
Age group, years, n (%)
18 to <65	29 (22)	11 (17)	40 (21)
≥65	101 (78)	54 (83)	155 (80)
≥75	40 (31)	21 (32)	61 (31)
Race, n (%)
Black or African American	2 (2)	2 (3)	4 (2)
White	107 (82)	50 (77)	157 (81)
Asian	12 (9)	6 (9)	18 (9)
Other	7 (5)	5 (8)	12 (6)
Missing	2 (2)	2 (3)	4 (2)
Ethnicity, n (%)
Hispanic or Latino	5 (4)	6 (9)	11 (6)
Not Hispanic or Latino	115 (89)	54 (83)	169 (87)
Not reported	9 (7)	3 (5)	12 (6)
Unknown	1 (< 1)	2 (3)	3 (2)
Region of participation, n (%)
Non-North American countries	113 (87)	53 (82)	166 (85)
Asia	11 (9)	6 (9)	17 (9)
Australasia	4 (3)	3 (5)	7 (4)
Europe	98 (75)	44 (68)	142 (73)
North America	17 (13)	12 (19)	29 (15)

Source: Adapted from FDA Review
Abbreviations: ITT, intent-to-treat; SD, standard deviation

What are the benefits of this drug? 

The benefits of OJJAARA were assessed by spleen shrinkage, improvement of the severity of symptoms, and reduction in the need for RBC transfusion in two trials (MOMENTUM and SIMPLIFY-1)

In MOMENTUM trial, reduction of the Total Symptom Score (TSS) by at least 50% was achieved by significantly higher percentage of patients treated with OJJAARA (25%) compared to danazol. Higher percentages of patients treated with OJJAARA compared to danazol, achieved transfusion independence (30% vs 20%). In addition, significantly higher percentage of patients treated with OJJAARA compared to danazol achieved spleen volume reduction of at least 25% (39% vs 6%, respectively).

Were there any differences in how well the drug worked in clinical trials among sex, race, and age? 

• Sex: The observed effect of OJJAARA was larger for females than males. However, because of limited size of the trial, this observed difference may be due to chance.
• Race: The majority of patients were White. The number of patients of other races was limited; therefore, differences in how well OJJAARA worked between races could not be determined.
• Age: The observed effect of OJJAARA was similar for patients younger and older than 65 years.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Observations of efficacy based on subgroups of the population studied are provided in Table 2 for MOMENTUM trial.

Table 2. MFSAF Version 4.0 TSS Response1 Rate at Week 24 by Subgroup, ITT Population, MOMENTUM

Subgroup	OJJAARA N=130 n/Ns (%)	Danazol N=65 n/Ns (%)	Difference % (95% CI)
Age group, years
<65	5/29 (17.2)	0/11 (0)	17.24 (-13.25, 36.11)
≥65	27/101 (26.7)	6/54 (11.1)	15.62 (0.56, 27.4)
Sex
Male	19/79 (24.1)	5/44 (11.4)	12.69 (-2.71, 25.93)
Female	13/51 (25.5)	1/21 (4.8)	20.73 (-1.4, 36.34)
Race2
Asian	4/12 (33.3)	0/6 (0)	33.33 (-17.56, 65.11)
Black or African American	0/2 (0)	0/2 (0)	0 (NC)
White	24/107 (22.4)	5/50 (10)	12.43 (-1.26, 23.56)
Other	4/7 (57.1)	1/5 (20)	37.14 (-23.75, 80)

Source: Adapted from FDA Review
¹MFSAF TSS response rate is defined as the proportion of subjects who achieve a ≥50% reduction in mean TSS over the consecutive 28-day period immediately prior to the end of Week 24, compared to baseline.
²Two patients in OJJAARA arm and two patients in Danazol arm had missing race information.
Abbreviations: CI, confidence interval; ITT, intent-to-treat; MFSAF, Myelofibrosis Symptom Assessment Form; N, number of patients in treatment arm; n, number of patients meeting criteria; NC, not computable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; TSS, Total Symptom Score

What are the possible side effects?

OJJAARA may be associated with serious and sometimes fatal infections. Other serious side effects include low blood platelets, low white blood cells, and abnormal liver tests.

The most common adverse reactions (≥20% in either study) are low platelet count, bleeding, bacterial infection, fatigue, dizziness, diarrhea, and nausea.

What are the possible side effects (results of trials used to assess safety)?

The side effects occurring in ≥5% of patients in the study where OJJAARA was used are detailed in Table 3 for MOMENTUM trial and Table 4 for SIMPLIFY-1 trial.

Table 3. Adverse Reactions Occurring in ≥5% of Patients During Randomized Treatment in MOMENTUM Trial

	OJJAARA, N=130		Danazola, N=65
Adverse Reaction	All Gradesb %	Grade ≥3 %	All Gradesb %	Grade ≥3 %
Thrombocytopeniac	28	22	17	12
Diarrheac	22	0	9	2
Hemorrhagec	22	2	18	8
Fatiguec	21	2	20	5
Nauseac	16	2	9	3
Bacterial infectionc,d	15	8	18	8
Abdominal painc	13	1	18	3
Viral infectionc,d	12	5	3	0
Pruritusc	11	2	11	0
Elevated liver enzymesc	10	2	9	3
Pyrexiac	10	2	8	0
Coughc	8	0	5	0
Paresthesiac	8	1	2	0
Dizzinessc	8	2	2	0
Vomitingc	8	1	0	0
Rashc	6	0	11	0
Renal and urinary tract infectionc,d	6	2	11	5
Arrhythmiac	5	1	6	2
Neutropenia	5	5	3	3

Source: OJJAARA Prescribing Information
^aStudy was not designed to evaluate meaningful comparisons of the incidence of adverse reactions across treatment groups.
^bAdverse reactions graded using CTCAE v.5.
^cGrouped term includes other related terms.
^dExcludes opportunistic infections.
Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events

Table 4. Adverse Reactions Occurring in ≥5% of Patients With Anemia during Randomized Treatment in SIMPLIFY-1 Trial

	OJJAARA, N=85 Baseline Hb <10 g/dL		Ruxolitiniba, N=95 Baseline Hb <10 g/dL
Adverse Reaction	All Gradesb %	Grade ≥3 %	All Gradesb %	Grade ≥3 %
Dizzinessc	24	1	15	2
Fatiguec	22	0	25	1
Bacterial infectionc,d	21	8	12	2
Hemorrhagec	21	1	18	2
Thrombocytopeniac	21	11	34	6
Diarrheac	20	1	20	1
Nauseac	20	0	3	1
Abdominal painc	18	1	14	1
Coughc	14	0	11	0
Hypotensionc	14	2	0	0
Pain in extremity	12	0	5	0
Pyrexiac	12	1	11	0
Rashc	12	0	3	0
Renal and urinary tract infectionc,d	12	1	4	0
Elevated liver enzymesc	11	4	9	0
Headachec	11	0	16	0
Peripheral edema	11	0	8	0
Arrhythmiac	8	2	2	1
Paresthesiac	8	0	3	0
Pneumoniac	8	8	5	3
Vomitingc	8	0	5	0
Back pain	7	1	2	0
Viral infectionc,d	6	0	13	2
Vitamin B1 deficiency	6	0	7	0

Source: OJJAARA Prescribing Information
^aStudy was not designed to evaluate meaningful comparisons of the incidence of adverse reactions across treatment groups.
^bAdverse reactions graded using CTCAE v.4.03.
^cGrouped term includes other related terms.
^dExcludes opportunistic infections
Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; Hb, hemoglobin

Were there any differences in side effects among sex, race, and age?

• Sex: Overall, the occurrence of side effects was similar between males and females. Females treated with OJJAARA experienced more nausea, and elevation of liver enzymes than male. 
• Race: The majority of participants were White. The number of patients of other races was limited; therefore, differences in the occurrence of side effects among races could not be determined.
• Age: The overall occurrence of side effects was similar in patients younger and older than 65 years of age. Patients aged 65 years or older experienced more low platelet count, hemorrhage and abdominal pain than younger patients.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 5. Adverse Reaction (≥5%) by Sex, MOMENTUM

	OJJAARA		Danazol
Adverse Reaction	Female N=51 %	Male N=79 %	Female N=21 %	Male N=44 %
Thrombocytopenia	27	28	14	18
Diarrhea	24	22	10	9
Hemorrhage	20	23	14	20
Fatigue	24	19	14	23
Nausea	27	9	5	11
Bacterial infection	8	19	33	11
Abdominal pain	14	13	24	16
Viral infection	10	13	0	5
Pruritus	10	11	10	11
Elevated liver enzymes	14	8	0	20
Pyrexia	6	13	14	5
Cough	8	9	0	7
Dizziness	8	8	0	2
Vomiting	10	6	0	0
Rash	0	10	10	11
Renal & urinary tract infection	6	6	24	5
Arrhythmia	6	5	5	7

Source: Adapted from FDA Review

Table 6. Adverse Reactions (≥5%) by Race, MOMENTUM

	OJJAARA				Danazol
Adverse Reactions	White N=107 %	Asian N=12 %	Black N=2 %	Other N=9 %	White N=50 %	Asian N=6 %	Black N=2 %	Other N=7 %
Thrombocytopenia	27	25	100	22	22	0	0	0
Diarrhea	23	17	0	22	10	0	0	14
Hemorrhage	22	0	50	33	20	0	50	14
Fatigue	21	17	0	22	22	0	0	29
Nausea	15	17	50	22	6	33	50	0
Bacterial infection	16	17	0	0	14	33	0	43
Abdominal pain	12	8	0	33	18	17	50	14
Viral infection	12	0	0	22	4	0	0	0
Pruritus	10	8	0	22	8	33	0	14
Elevated liver enzymes	8	0	100	22	10	33	50	14
Pyrexia	9	8	0	22	8	17	0	0
Cough	7	8	0	33	0	17	100	0
Paresthesia	7	8	50	0	0	0	50	14
Dizziness	7	17	50	0	2	0	0	0
Vomiting	5	25	0	22	0	0	0	0
Rash	6	8	0	11	12	17	0	0
Renal & urinary tract infection	7	0	0	0	10	17	0	14
Arrhythmia	6	0	0	11	4	33	0	0

Source: Adapted from FDA Review

Table 7. Adverse Reactions (≥5%) by Age, MOMENTUM

	OJJAARA		Danazol
Adverse Reaction	19 to 64 Years N=29 %	≥65 Years N=101 %	19 to 64 Years N=11 %	≥65 Years N=54 %
Thrombocytopenia	10	33	9	19
Diarrhea	24	22	0	11
Hemorrhage	7	26	18	19
Fatigue	17	22	18	20
Nausea	14	17	27	6
Bacterial infection	14	15	27	17
Abdominal pain	7	15	36	15
Viral infection	21	9	0	4
Pruritus	10	11	9	11
Elevated liver enzymes	7	11	36	4
Pyrexia	7	11	9	7
Cough	7	9	18	2
Paresthesia	10	7	9	0
Dizziness	7	8	0	2
Vomiting	7	8	0	0
Rash	3	7	18	9
Renal & urinary tract infection	7	6	9	11
Arrhythmia	3	6	18	4

Source: Adapted from FDA Review

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.

COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.

EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.

PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

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