Myocardial infarction; A PHASE II TRIAL    This is a report from an interventional study source for Protocol sponsored by BioNTech, managed and reported by Pfizer on the sponsor's behalf. Other Case identifier(s): US-BNTAG-1602 (BioNTech). Case No.: 00001602 Sponsor Study Case No.: BNT162-17_0015 AE No. in CRF: not provided Site No.: redacted Country: Patient No.: redacted Initial information received on 24-May-2022/26-May-2022: This is a serious case of myocardial infarction (MedDRA PT: myocardial infarction) from clinical trial BNT162-17, classified as serious adverse event of special interest (SAESI). A 58-year-old male subject received one booster injection with study drug BNT162b2 (B.1.1.7 +B.1.617.2) (BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2)) on 29-Nov-2021 with a dose of 30 mcg for SARS-CoV-2 vaccination. Previously the patient had received two injections of 30 mcg Comirnaty (BNT162b2) on 08-Feb-2021 and 01-Mar-2021 each time with a dose of 30 mcg. 69 days after start of treatment with BNT162b2 (B.1.1.7 +B.1.617.2) the patient experienced myocardial infarction (myocardial infarction) on 06-Feb-2022. This case is serious due to inpatient hospitalisation and due to being another medically important condition. Relevant medical history includes hypertension from 2016, hypercholesterolemia from 2020 and vasectomy in 2003. Relevant concomitant medication includes Hydrochlorothiazide (hydrochlorothiazide), Lisinopril (lisinopril) and Amlodipine (amlodipine) all administered for hypertension and Atorvastatin (atorvastatin) administered for hypercholesterolemia. On 06-Feb-2022 the patient experienced chest pain (chest pain) and tightness (chest discomfort). He called the emergency and was transported to the hospital via an ambulance. While in the emergency department Troponin levels were drawn every hour for three (3) hours and each time the value increased. The patient was admitted to the Cardiac Unit and was diagnosed with a myocardial infarction (myocardial infarction) of severe intensity (FDA Guidance 2007. FDA Guidance for Industry. Toxicity Grading Scale). A 2-dimensional Doppler echocardiography of the heart was performed on 07-Feb-2022 and showed normal left ventricular size with wall thickness. The patient had a cardiac catheterization on 07-Feb-2022 and 08-Feb-2022, and on 08-Feb-2022 patient had a stent placed. The patient has recovered well on 08-Feb-2022 and was discharged on 09-Feb-2022. Since 09-Feb-2022 he was treated with Brilinta (ticagrelor) (180 mg/d), Rosuvastatin (rosuvastatin) (40 mg), Metoprolol (metoprolol) (50 mg/d), Aspirin (acetylsalicylic acid) (81 mg/d) and Nitroglycerin (glyceryl trinitrate) (0.4 mg as necessary). The investigator became aware of the event on 24-May-2022. At the time of reporting, the main event has resolved with date of 08-Feb-2022. No further information is available at that time. Additional information has been requested.   BNT162B2 is under agreement with BioNTech.  Causality Assessments of BNT162B2 for Myocardial infarction per reporter was no reasonable possibility; per Company (BIONTECH) was no reasonable possibility.  Follow-up (22Sep2022): This is a follow-up report from an interventional study source for Protocol sponsored by BioNTech, managed and reported by Pfizer on the sponsor's behalf. Other Case identifier(s): 2022FOS003869 (Agency), 160414328 (Pfizer Inc), US-BNTAG-1602 (BioNTech):  Additional information dated on 16-Sep-2022: Administrative update: The format of the site number was updated according to current format from '02' to '840-02' via creation of a subversion. The medical assessment remained unchanged.  Causality Assessments of BNT162B2 for Myocardial infarction per reporter was no reasonable possibility; per Company (BIONTECH) was no reasonable possibility.  Follow-up (28Sep2022): This is a follow-up report from an interventional study source for Protocol sponsored by BioNTech, managed and reported by Pfizer on the sponsor's behalf. Other Case identifier(s): US-BNTAG-1602 (BioNTech). Updated information included: The patient received 90 mg of Brilinta (ticagrelor) twice daily; thus, a daily dose of 180 mg/d was administered.  Follow-up (24May2022): This is a follow-up report from an interventional study source for Protocol sponsored by BioNTech, managed and reported by Pfizer on the sponsor's behalf. Other Case identifier(s): 2022FOS003869 (Agency), US-BNTAG-1602 (BioNTech).  Additional information dated on 18-Oct-2022: Administrative update: Due to general renaming of the drug name "Multivalent BNT162b2 (B.1.1.7 +B.1.617.2)" to "BNT162b2 (B.1.1.7 + B.1.617.2)" the drug name was adapted accordingly in the current case via creation of a subversion. The medical assessment remained unchanged.  Follow-up (21Mar2023): This is a follow-up report from an interventional study source for Protocol  sponsored by BioNTech, managed and reported by Pfizer on the sponsor's behalf. Other Case identifier(s): 172107957 (Pfizer Inc), US-BNTAG-1602 (BioNTech). Follow-up information received on 21-Mar-2023: It was confirmed that patient discontinued use of Atorvastatin at the time of the SAE onset (08-Feb-2022). Relevant concomitant medication started on 09-Feb-2022 and is ongoing. No further information was provided. BioNTech Comment: The reporting investigator considers the event to be serious due to inpatient hospitalisation and due to being medically important condition. The sponsor agrees to the investigator's assessment. Myocardial infarction is not listed in the currently valid reference safety information of the study drug BNT162b2-based multivalent vaccine (Investigator's Brochure, version 1.0, dated 15 Jul 2021). Hence, the case is assessed as unexpected on case level. The reporting investigator assessed myocardial infarction as not related to the treatment with BNT162b2 (B.1.1.7 +B.1.617.2) (BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2)). The sponsor agrees to the investigator's assessment. Temporal relationship to treatment with the study drug is not plausible since acute myocardial infarction with symptoms of chest pain and chest tightness occurred 69 days after the vaccination. Patient's medical history of hypertension, hypercholesterolemia, obesity and older age presents risk factors for the occurrence of a myocardial infarction. Additionally, surgical intervention of cardiac catheterisation and stent placement indicates to underlying coronary artery disease as primary cause for myocardial infarction presenting a plausible and alternative explanation. Further details via the hospital discharge report is requested. The benefit-risk profile of BNT162b2 (B.1.1.7 +B.1.617.2) (BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2)) is not affected by this event and no change in the reference safety information is required at that time. Medical re-assessment after FU1 received 21-Mar-2023: The case is still assessed as serious due to hospitalization and due to being medically important condition by the reporting investigator and the sponsor. The new information does not change the causality assessment, which remains not related by the investigator and the sponsor. The expectedness is always assessed based on the reference safety information valid at the time of the initial report and is therefore not changed in the re-assessment. Hence, the case is still assessed as unexpected on case level. The benefit-risk profile of BNT162b2(B.1.1.7 + B1.617.2) is still not affected by this event and no change in the reference saftey information is required at this time.  BNT162B2 is under agreement with BIONTECH.  Follow-up (05Apr2023): This is a follow-up report from an interventional study source for Protocol sponsored by BioNTech, managed and reported by Pfizer on the sponsor's behalf. Other Case identifier(s): US-BNTAG-1602 (BioNTech) . Updated information includes: Hydrochlorothiazide (hydrochlorothiazide), Lisinopril (lisinopril) and Amlodipine (amlodipine) were past drugs (previously mentioned as concomitant medication).  BNT162B2 is under agreement with BIONTECH.  Follow-up (23Aug2023): This is a non-Pfizer sponsored interventional study follow-up report from License Party (BioNTech) for protocol. Other Case identifier(s): 2022FOS003869 (Agency), US-BNTAG-1602 (BioNTech ). Follow-up information received on 23-Aug-2023: According to the site, the SAE occurred while the subject was out of the state. The subject is unreachable, did not sign a medical release, and has not returned to the site since the SAE occurred. The subject is also not responding to the site's request to obtain the medical records. The site has attempted on more than three occasions without success to obtain the subject's records. This is a Lost to Follow up (LTFU) and the site was instructed to document the LTFU according to section 7.3 of the clinical trial protocol. No further information is available.  BioNTech Comment: Medical re-assessment after follow-up information received 23-Aug-2023 (FU2): This is a not related case imported from the former database where expectedness was assessed as not applicable. With the follow-up information received, the previous medical assessment provided on 21-Mar-2023 has not changed. The information in this single case does not change the benefit-risk profile of BNT162b2 or warrant any changes to the conduct of this trial.  BNT162B2 is under agreement with BIONTECH.  BioNTech Causality Assessment to BNT162B2: myocardial infarction was unrelated to BNT162B2 per reporter and company.; Sender's Comments: BioNTech Comment: The reporting investigator considers the event to be serious due to inpatient hospitalisation and due to being another medically important condition The sponsor agrees to the investigator's assessment. Myocardial infarction is not listed in the currently valid reference safety information of the study drug BNT162b2-based multivalent vaccine (Investigator's Brochure, version 1.0, dated 15 Jul 2021). Hence, the case is assessed as unexpected on case level. The reporting investigator assessed myocardial infarction as not related to the treatment with Multivalent BNT162b2 (B.1.1.7 +B.1.617.2) (BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2)). The sponsor agrees to the investigator's assessment. Temporal relationship to treatment with the study drug is not plausible since acute myocardial infarction with symptoms of chest pain and chest tightness occurred 69 days after the vaccination. Patient's medical history of hypertension, hypercholesterolemia, obesity and older age presents risk factors for the occurrence of a myocardial infarction. Additionally, surgical intervention of cardiac catheterisation and stent placement indicates to underlying coronary artery disease as primary cause for myocardial infarction presenting a plausible and alternative explanation. Further details via the hospital discharge report is requested. The benefit-risk profile of Multivalent BNT162b2 (B.1.1.7 +B.1.617.2) (BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2)) is not affected by this event and no change in the reference safety information is required at that time.