Approved Risk Evaluation and Mitigation Strategies (REMS)

Tegsedi (Inotersen)

NDA #211172

REMS last update: 11/22/2024

Goals
Summary
REMS Materials
Assessment Plan
Update history

What is the purpose of the REMS?

The goal of the Tegsedi REMS is to mitigate the risk of serious bleeding with severe thrombocytopenia and the risk of glomerulonephritis associated with Tegsedi by:

Ensuring prescribers are educated on the risk of serious bleeding with severe thrombocytopenia and the risk of glomerulonephritis associated with Tegsedi.

Ensuring prescribers are educated and adhere to the following:
- Counsel patients on how to recognize and respond to signs and symptoms of serious bleeding and glomerulonephritis.
- Enroll patients in the Tegsedi REMS Program.
- Submit documentation that periodic monitoring of patients is being done to identify severe thrombocytopenia, serious bleeding with severe thrombocytopenia, and glomerulonephritis.
Ensuring patients are informed on the following:
- How to recognize and respond to signs and symptoms of serious bleeding and glomerulonephritis.
- The need to have their platelet count and renal function monitored.
Enrollment of all patients in a registry to further support long-term safety and safe use of TEGSEDI.

What do participants need to know?

Below is a general overview of the REMS for all REMS participants (e.g., patients, pharmacies, and healthcare providers). See the application holder(s) REMS Website or the approved REMS materials for more information.

View application holder(s) REMS Website

Healthcare providers who prescribe TEGSEDI must:

To become certified to prescribe	Review the drug’s Prescribing Information. Review the following: Prescriber Training and Program Overview. Successfully complete the Prescriber Knowledge Assessment and submit it to the REMS. Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS.
Before treatment initiation (first dose)	Counsel the patient on how to recognize and respond to signs and symptoms of serious bleeding and glomerulonephritis and the need to have their platelet count and renal function monitored, using the Patient Guide and Wallet Card. Provide the patient with the Patient Guide and Wallet Card. Assess the patient’s platelet count and appropriateness of initiating treatment. Document and submit to the REMS using the Patient Enrollment Form. Assess the patient’s estimated glomerular filtration rate (eGFR), urinalysis, and urine protein to creatinine ratio (UPCR) and appropriateness of initiating treatment. Document and submit to the REMS using the Patient Enrollment Form. Enroll the patient by completing and submitting the Patient Enrollment Form to the REMS. Provide a completed copy of the form to the patient.
During treatment; weekly or more frequently as described in the Prescribing Information	Assess the patient’s platelet count and appropriateness of continuing treatment.
During treatment; every two weeks	Assess the patient’s estimated glomerular filtration rate (eGFR), urinalysis, and urine protein to creatinine ratio (UPCR) and appropriateness of continuing treatment.
During treatment; every 90 days	Assess the patient’s platelet count, signs and symptoms of thrombocytopenia, and appropriateness of continuing treatment. Document and submit to the REMS using the Patient Status Form. Assess the patient's estimated glomerular filtration rate (eGFR), urinalysis, urine protein to creatinine ratio (UPCR), signs and symptoms of renal toxicity, and appropriateness of continuing treatment. Document and submit to the REMS using the Patient Status Form.
After treatment discontinuation; weekly for 8 weeks or more frequently as described in the Prescribing Information	Assess the patient's platelet count.
After treatment discontinuation; every 2 weeks for 8 weeks	Assess the patient’s estimated glomerular filtration rate (eGFR), urinalysis, and urine protein to creatinine ratio (UPCR).
After treatment discontinuation; at 8 weeks	Assess the patient’s platelet count and signs and symptoms of thrombocytopenia. Document and submit to the REMS using the Patient Status Form. Assess the patient’s estimated glomerular filtration rate (eGFR), urinalysis, urine protein to creatinine ratio (UPCR), and signs and symptoms of renal toxicity. Document and submit to the REMS using the Patient Status Form.
At all times	Report events of severe thrombocytopenia, serious bleeding with severe thrombocytopenia, and glomerulonephritis to the REMS. Report treatment discontinuation or transfer of care to the REMS using the Patient Status Form.

Patients who are prescribed TEGSEDI:

Before treatment initiation (first dose)	Review the Patient Guide and Wallet Card. Enroll in the REMS by completing the Patient Enrollment Form with the Get a blood test to check platelet count and blood and urine tests to check kidneys. Receive counseling from the prescriber on the risk of serious bleeding, the risk of kidney inflammation (glomerulonephritis), and the need to complete the appropriate laboratory testing using the Patient Guide and Wallet Card.
During treatment; every week or more often as directed by the prescriber	Get a blood test to check platelet count.
During treatment; every two weeks	Get blood and urine tests to check kidneys.
After treatment discontinuation; weekly for 8 weeks or more often as directed by the prescriber	Get a blood test to check platelet count.
After treatment discontinuation; every 2 weeks for 8 weeks	Get blood and urine tests to check kidneys.
At all times	Inform the prescriber of any serious bleeding or signs and symptoms of kidney inflammation. Have the Wallet Card with you. Inform all healthcare providers about receiving this treatment.

Pharmacies that dispense TEGSEDI must:

To become certified to dispense	Designate an authorized representative to carry out the certification process and oversee implementation and compliance with the REMS on behalf of the pharmacy. Have the authorized representative review the Program Overview. Have the authorized representative enroll in the REMS by completing the Pharmacy Enrollment Form and submitting it to the REMS. Train all relevant staff involved in the dispensing of TEGSEDI on the program requirements using the Program Overview. Establish processes and procedures to dispense no more than a 30 day supply. Establish processes and procedures to report severe thrombocytopenia, serious bleeding with severe thrombocytopenia, and glomerulonephritis events to the REMS.
Before dispensing	Obtain authorization to dispense each prescription by contacting the REMS to verify the prescriber is certified and the patient is enrolled and authorized to receive the drug. Dispense no more than a 30 day supply.
To maintain certification to dispense	Have a new authorized representative enroll in the REMS by completing the Pharmacy Enrollment Form and submitting it to the REMS if the authorized representative changes.
At all times	Report severe thrombocytopenia, serious bleeding with severe Not distribute, transfer, loan, or sell TEGSEDI, except to certified dispensers. Maintain records documenting staff’s completion of REMS training. Maintain records that all REMS processes and procedures are in place and are being followed. Comply with audits carried out by Akcea Therapeutics or a third party acting on behalf of Akcea Therapeutics to ensure all processes and procedures are in place and are being followed.

Wholesalers-distributors that distribute TEGSEDI must:

To be able to distribute	Establish processes and procedures to ensure the drug is distributed only to certified pharmacies. Train all relevant staff involved in distributing on the program requirements.
At all times	Distribute only to certified pharmacies. Maintain records of all distributions. Comply with audits carried out by Akcea Therapeutics or a third party acting on behalf of Akcea Therapeutics to ensure all processes and procedures are in place and are being followed.

What materials are included in the REMS?

The REMS includes a REMS Document. In addition, the REMS includes the following materials intended for patients and healthcare providers. For a specific Medication Guide of a product in the Tegsedi REMS, see the DailyMed link(s).

Material Name	Material Name Link
Healthcare Provider Reminder Letter for Patient Status Form Submission (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Healthcare_Provider_Reminder_Letter_for_Patient_Status_Form_Submission.pdf
Patient Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Patient_Enrollment_Form.pdf
Patient Guide (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Patient_Guide.pdf
Patient Status Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Patient_Status_Form.pdf
Pharmacy Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Pharmacy_Enrollment_Form.pdf
Prescriber Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Prescriber_Enrollment_Form.pdf
Prescriber Knowledge Assessment (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Prescriber_Knowledge_Assessment.pdf
Prescriber Training (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Prescriber_Training.pdf
Program Overview (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Program_Overview.pdf
REMS Document (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_REMS_Document.pdf
REMS Full (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_REMS_Full.pdf
REMS Website (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_REMS_Website.pdf
Wallet Card (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2024_11_22_Wallet_Card.pdf

Assessment Plan
This webpage provides REMS assessment plan measures, metrics, and indicators for drug and biological products with a REMS. The REMS assessment plan measures, metrics, and indicators are part of the overall REMS assessment plan used by FDA to evaluate the performance of a REMS and are included in FDA approval letters. The current REMS assessment plan measures, metrics, and indicators are extracted from regulatory letters that contain REMS information, including FDA approval letters, and posted here as they become available.

Assessment Plan

This webpage provides REMS assessment plan measures, metrics, and indicators for drug and biological products with a REMS. The REMS assessment plan measures, metrics, and indicators are part of the overall REMS assessment plan used by FDA to evaluate the performance of a REMS and are included in FDA approval letters. The current REMS assessment plan measures, metrics, and indicators are extracted from regulatory letters that contain REMS information, including FDA approval letters, and posted here as they become available.

What updates have been made to the REMS?

Date	Summary of change
11/22/2024	Modified to: 1. Update the Tegsedi REMS materials to align with the labeling changes pertaining to the risk of thrombocytopenia approved on January 12, 2024 under Supplement 14. 2. Add a pop-up notification to the REMS Website to inform stakeholders of Akcea’s process to discontinue commercial availability of Tegsedi in the United States effective September 27, 2024. 3. Update the adverse event reporting phone number.
08/24/2023	Revised to update REMS Coordinating Center address
03/08/2023	Modified to: Add the Healthcare Provider Reminder Letter for Patient Status Form Submission as a new REMS material and changes to the REMS Document to reflect the requirement to disseminate this letter. Update the existing Prescriber Training to add the Patient Status Form Timing Requirements Reminder Sheet chart as an appendix.
09/14/2022	Revised to make an editorial change
03/31/2022	Modified to reflect (a) revisions to the REMS Forms to align with the change in the US distributor for Tegsedi from Akcea Therapeutics to Sobi Inc., and (b) addition of a question to the Prescriber Knowledge Assessment to test prescriber knowledge that Tegsedi should generally not be initiated in patients who develop a urinary protein to creatinine ratio (UPCR) of 1000 mg/g or higher.
05/11/2020	Modified to make: Changes to the Prescriber Enrollment Form that include the addition of name and contact information fields related to prescriber delegates. Updates to the Patient Status Form including a section that indicates the form may be submitted by a prescriber delegate and the ability of the prescriber to choose from a range of platelet counts to further clarify the level of thrombocytopenia that led to discontinuation. Updates to the Prescriber Knowledge Assessment to revise the answer to one of the questions. Revised to make editorial changes.
10/05/2018	Approval of REMS. Revised to reflect change in ownership.

Disclaimer: This webpage provides general information about REMS programs to various REMS participants (e.g., patients, pharmacies, and healthcare providers). The summary information provided herein is not comprehensive and may not include all of the information relevant to REMS participants. This webpage does not constitute a replacement, modification, or revision of the approved REMS document, including any appended REMS materials. Refer to the approved REMS document for complete information on the REMS requirements for each approved application.

Tegsedi (Inotersen) NDA #211172 REMS last update: 11/22/2024