Trial Outcomes & Findings for Study to Evaluate Efficacy and Safety of Benralizumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma (NCT NCT03557307)

Last Updated: 2023-06-06

Results Overview

Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

598 participants

Primary outcome timeframe

Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)

Results posted on

2023-06-06

Participant Flow

705 participants provided informed consent and were assigned a unique enrollment number prior to screening. Of the 705 patients screened, 598 (84.8%) were eligible to receive Benralizumab 30 mg and entered the study. All 598 (100%) patients received the study drug. 195 of the 538 patients who completed the main study treatment enrolled into PONENTE Long Term Follow Up Substudy.

In PONENTE, at the first visit, ie, the enrollment visit 1, patients were assigned an enrollment number and then evaluated regarding the protocol mandated inclusion and exclusion criteria. After screening and evaluation, only those eligible to receive Benralizumab 30 mg were assigned treatment and entered a 4 week induction phase on a stable dose of oral corticosteroids (OCS). In Substudy, patients were treated according to healthcare provider discretion with no IP provided by sponsor.

Participant milestones

Participant milestones
Measure	Benra 30 mg For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.
Period 1: To End of OCS Reduction Phase STARTED	598
Period 1: To End of OCS Reduction Phase COMPLETED	563
Period 1: To End of OCS Reduction Phase NOT COMPLETED	35
Period 2: Maintenance Phase STARTED	563
Period 2: Maintenance Phase COMPLETED	536
Period 2: Maintenance Phase NOT COMPLETED	27
Period 3: Long Term Follow up Substudy STARTED	195
Period 3: Long Term Follow up Substudy Asthma Treatment as Per Healthcare Provider Discretion	195
Period 3: Long Term Follow up Substudy >=50% Any Biologic	78
Period 3: Long Term Follow up Substudy >=50% Benra	69
Period 3: Long Term Follow up Substudy COMPLETED	195
Period 3: Long Term Follow up Substudy NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Benra 30 mg For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.
Period 1: To End of OCS Reduction Phase Withdrawal by Subject	10
Period 1: To End of OCS Reduction Phase Adverse Event	7
Period 1: To End of OCS Reduction Phase Protocol Violation	6
Period 1: To End of OCS Reduction Phase Lost to Follow-up	5
Period 1: To End of OCS Reduction Phase other	3
Period 1: To End of OCS Reduction Phase Death	2
Period 1: To End of OCS Reduction Phase Failure to meet inclusion/exclusion criteria	2
Period 2: Maintenance Phase Adverse Event	4
Period 2: Maintenance Phase Death	3
Period 2: Maintenance Phase Lost to Follow-up	2
Period 2: Maintenance Phase Pregnancy	2
Period 2: Maintenance Phase Protocol Violation	11
Period 2: Maintenance Phase Withdrawal by Subject	2
Period 2: Maintenance Phase other	3

Baseline Characteristics

Race of 9 patients in Full Analysis Set is not recorded.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Benra 30 mg n=598 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.
Age, Continuous	53.3 years STANDARD_DEVIATION 13.59 • n=598 Participants
Sex: Female, Male Female	383 Participants n=598 Participants
Sex: Female, Male Male	215 Participants n=598 Participants
Race/Ethnicity, Customized White	475 Participants n=589 Participants • Race of 9 patients in Full Analysis Set is not recorded.
Race/Ethnicity, Customized Black or African American	26 Participants n=589 Participants • Race of 9 patients in Full Analysis Set is not recorded.
Race/Ethnicity, Customized Asian	29 Participants n=589 Participants • Race of 9 patients in Full Analysis Set is not recorded.
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=589 Participants • Race of 9 patients in Full Analysis Set is not recorded.
Race/Ethnicity, Customized American Indian or Alaska Native	46 Participants n=589 Participants • Race of 9 patients in Full Analysis Set is not recorded.
Race/Ethnicity, Customized Other	12 Participants n=589 Participants • Race of 9 patients in Full Analysis Set is not recorded.

PRIMARY outcome

Timeframe: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)

Population: Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.

Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg n=598 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Patients Who Achieve 100% Reduction in Daily OCS Dose	376 Participants	—	—

PRIMARY outcome

Population: All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.

Patients who achieve 100% reduction or a daily OCS dose of \<=5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg n=598 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg	490 Participants	—	—

SECONDARY outcome

Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg n=598 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Patients Who Achieve a Daily OCS of ≤5mg	547 Participants	—	—

SECONDARY outcome

Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg n=598 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose ≥90% reduction	383 Participants	—	—
Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose ≥75% reduction	412 Participants	—	—
Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose ≥50% reduction	489 Participants	—	—

SECONDARY outcome

Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase

Outcome measures

Outcome measures
Measure	Benra 30 mg n=593 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Change From Baseline in Average Daily OCS Dose (mg)	-8.50 mg Interval -9.1 to -7.9	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.

Population: Long term follow up analysis set - All patients who enrolled in Long Term Follow Up substudy

Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg n=195 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic n=78 Participants \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra n=69 Participants \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Patients Who Achieve 100% Reduction in Daily OCS Dose From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy	138 Participants	60 Participants	54 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.

Population: Long Term Follow Up analysis set - All patients who enrolled in Long Term Follow Up substudy

Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg n=195 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic n=78 Participants \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra n=69 Participants \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Patients Who Achieve a Daily OCS Dose of ≤5 mg at the End of the Long Term Follow up Substudy	177 Participants	72 Participants	65 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.

Population: Long Term Follow Up analysis set - All patients who enrolled in Long Term Follow Up substudy

Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg n=195 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic n=78 Participants \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra n=69 Participants \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy >=90% reduction	141 Participants	61 Participants	55 Participants
Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy >=75% reduction	151 Participants	64 Participants	58 Participants
Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy >=50% reduction	172 Participants	71 Participants	64 Participants
Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy >0% reduction	175 Participants	72 Participants	65 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.

Population: Long Term Follow Up analysis set - All patients who enrolled in Long Term Follow Up substudy

Change in average daily OCS dose (mg) from main study baseline to the end of the long term follow up substudy

Outcome measures

Outcome measures
Measure	Benra 30 mg n=195 Participants For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics.	>=50% Any Biologic n=78 Participants \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra n=69 Participants \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
Change in Daily OCS Dose (mg) From Main Study Baseline to the End of the Long Term Follow up Substudy	-10.01 mg Interval -11.26 to -8.76	-10.28 mg Interval -12.16 to -8.41	-10.8 mg Interval -12.85 to -8.75

Adverse Events

Benra 30 mg

Serious events: 89 serious events

Other events: 181 other events

Deaths: 5 deaths

Asthma Treatment as Per Healthcare Provider Discretion

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

>=50% Any Biologic

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

>=50% Benra

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Benra 30 mg n=598 participants at risk For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks.	Asthma Treatment as Per Healthcare Provider Discretion n=195 participants at risk Treated as per healthcare provider's discretion, including Benra 30 mg administered every 4 to 8 weeks or other biologics. IP or medications were not provided by the sponsor.	>=50% Any Biologic n=78 participants at risk \>=50% exposure to any biologic treatment for asthma from the end of maintenance phase of the main study to the Long Term Follow Up visit	>=50% Benra n=69 participants at risk \>=50% exposure to benralizumab from the end of maintenance phase of the main study to the Long Term follow Up visit, and no previous or concurrent exposure to any other biologic during this period
General disorders Influenza like illness	5.5% 33/598 • Number of events 34 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/195 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/78 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/69 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.
Infections and infestations Nasopharyngitis	10.7% 64/598 • Number of events 92 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/195 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/78 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/69 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.
Infections and infestations Sinusitis	3.2% 19/598 • Number of events 22 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/195 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/78 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/69 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.
Infections and infestations Upper respiratory tract infection	4.2% 25/598 • Number of events 28 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/195 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/78 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/69 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.
Infections and infestations Viral upper respiratory tract infection	4.7% 28/598 • Number of events 31 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/195 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/78 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/69 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.
Nervous system disorders Headache	4.8% 29/598 • Number of events 38 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/195 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/78 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/69 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.
Vascular disorders Hypertension	3.5% 21/598 • Number of events 21 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/195 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/78 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.	0.00% 0/69 • Main study: From first dose of study drug until end of study, with an average of 405 days. Substudy: on-study period, between the date of informed consent for the substudy and the last available visit or contact for a patient, with an average of 18 days.

Additional Information

Maria Jison, MD Global Clinical Head, FASENRA, Late-stage R&I

AstraZeneca

Phone: +13013980340

Email: [email protected]

Results disclosure agreements

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