Zynteglo

Procedure started
Under evaluation
PRAC recommendation
CAT draft opinion
CHMP opinion
European Commission final decision

Current status

European Commission final decision

Overview

CHMP endorses review finding no link between viral vector in Zynteglo and blood cancer

On 22 July 2021, EMA’s human medicines committee (CHMP) endorsed findings of a review which concluded that there is no evidence Zynteglo causes a blood cancer known as acute myeloid leukaemia (AML).

Zynteglo, a gene therapy for the blood disorder beta thalassaemia, uses a viral vector (or modified virus) to deliver a working gene into the patient’s blood cells.

The review considered two cases of AML in patients treated with an investigational medicine, bb1111, in a clinical trial for sickle cell disease. Although there have been no reports of AML with Zynteglo, both medicines use the same viral vector and there was a concern that the vector may be implicated in the development of the cancer (insertional oncogenesis).

The review by EMA’s safety committee (PRAC) supported by experts from the Committee for Advanced Therapies (CAT) found that the viral vector was unlikely to be the cause. In one of the patients, the viral vector was not present in the cancer cells, and in the other patient it was present at a site (VAMP4) that does not appear to be involved in cancer development.

After examining all the evidence, it was clear that more plausible explanations for the AML cases included the conditioning treatment the patients received to clear out bone marrow cells and the higher risk of blood cancer in people with sickle cell disease.

Patients having Zynteglo treatment for beta thalassaemia also need conditioning treatment to clear out their bone marrow cells before receiving Zynteglo. Healthcare professionals should therefore explicitly inform patients receiving Zynteglo of the increased risk of blood cancers from medicines used in conditioning treatments.

The CHMP agreed on an update of recommendations for monitoring patients. Healthcare professionals should now check their patients for signs of blood cancers at least once a year for 15 years.¹

The CHMP concluded that the benefits of Zynteglo continue to outweigh its risks. As for all medicines, the EMA will monitor any new data on its safety and update advice for patients and healthcare professionals when necessary.

¹ The previous recommendation was for healthcare professionals to check for signs of cancer once a year.

An EMA review has found no evidence that the viral vector in Zynteglo causes a blood cancer known as acute myeloid leukaemia (AML).
Zyntelgo will continue to be used as before. Your healthcare professional may, however, invite you for cancer screening more frequently than once a year.
If you have any question about your treatment, speak to your healthcare professional.

EMA’s review has concluded that there is no evidence that the viral vector in Zynteglo causes AML.
Although two patients who received the same viral vector in another medicine had AML, there are more plausible explanations than insertional oncogenesis, including the conditioning treatment the patients received and the higher risk of haematological cancer in people with sickle cell disease.
Healthcare professionals should explicitly inform patients receiving Zynteglo of the increased risk of blood cancers from medicines used in conditioning treatments.
Healthcare professionals should continue monitoring patients for cancer. EMA has updated its recommendation for cancer screening, changing the requirement from once a year to at least once a year.

: Zynteglo is a one-time treatment for a blood disorder known as beta thalassaemia in patients 12 years and older who require regular blood transfusions.
To make Zynteglo, the stem cells taken from the patient’s blood are modified by a virus that carries working copies of the beta-globin gene into the cells. When these modified cells are given back to the patient, they are transported in the bloodstream to the bone marrow where they start to make healthy red blood cells that produce beta-globin. The effects of Zynteglo are expected to last for the patient’s lifetime.
Zynteglo was granted conditional marketing authorisation in May 2019. The conditional authorisation means that there is more evidence to come about the medicine, which the company will provide. EMA regularly reviews new information that becomes available.

: The review of Zynteglo was initiated on 18 February, 2021 at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.
The review was first carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the committee responsible for the evaluation of safety issues for human medicines, which worked closely with experts from the Committee for Advanced Therapies (CAT).
The PRAC recommendations were sent to the CAT, which adopted a draft opinion on 16 July 2021 in line with the PRAC recommendations, and subsequently to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use. On 22 July 2021, the CHMP adopted the Agency’s final opinion taking into account the draft opinion of the CAT. The CHMP opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 16 September 2021.

List item

Zynteglo Article-20 referral - CHMP endorses review finding no link between viral vector in Zynteglo and blood cancer (PDF/1.25 MB)

First published: 23/07/2021
Last updated: 04/10/2021
EMA/546292/2021
- Bulgarian
  (PDF/1.91 MB)
- Croatian
  (PDF/1.85 MB)
- Czech
  (PDF/1.9 MB)
- Danish
  (PDF/1.85 MB)
- Dutch
  (PDF/1.83 MB)
- Estonian
  (PDF/1.82 MB)
- Finnish
  (PDF/1.82 MB)
- French
  (PDF/1.83 MB)
- German
  (PDF/1.83 MB)
- Greek
  (PDF/1.92 MB)
- Hungarian
  (PDF/1.9 MB)
- Italian
  (PDF/1.82 MB)
- Latvian
  (PDF/1.89 MB)
- Lithuanian
  (PDF/1.85 MB)
- Maltese
  (PDF/1.92 MB)
- Polish
  (PDF/1.9 MB)
- Portuguese
  (PDF/1.83 MB)
- Romanian
  (PDF/1.85 MB)
- Slovak
  (PDF/1.9 MB)
- Slovenian
  (PDF/1.89 MB)
- Spanish
  (PDF/1.83 MB)
- Swedish
  (PDF/1.83 MB)

Key facts

About this medicine
Approved name	Zynteglo
International non-proprietary name (INN) or common name	betibeglogene autotemcel
Associated names	Zynteglo
Class	Haematological agents

About this procedure
Current status	European Commission final decision
Reference number	EMEA/H/A-20/1504/C/003691/0023
Type	Article 20 procedures This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.
Authorisation model	Centrally authorised product(s)
Decision making model	PRAC-CAT-CHMP-EC

Key dates and outcomes
Procedure start date	11/03/2021
PRAC recommendation date	09/07/2021
CHMP opinion/CMDh position date	22/07/2021
EC decision date	16/09/2021
Outcome	Risk minimisation measures

All documents

Procedure started

Zynteglo Article-20 referral - Review of thalassaemia medicine Zynteglo started (PDF/701.84 KB)

First published: 12/03/2021
EMA/127031/2021

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Zynteglo Article-20 referral - EMA finds no evidence linking viral vector in Zynteglo to blood cancer (PDF/702.81 KB)

First published: 09/07/2021
EMA/380481/2021

Opinion provided by Committee for Medicinal Products for Human Use

Zynteglo Article-20 referral - CHMP endorses review finding no link between viral vector in Zynteglo and blood cancer (PDF/1.25 MB)

First published: 23/07/2021
Last updated: 04/10/2021
EMA/546292/2021

Bulgarian
(PDF/1.91 MB)
Croatian
(PDF/1.85 MB)
Czech
(PDF/1.9 MB)
Danish
(PDF/1.85 MB)
Dutch
(PDF/1.83 MB)
Estonian
(PDF/1.82 MB)
Finnish
(PDF/1.82 MB)
French
(PDF/1.83 MB)
German
(PDF/1.83 MB)
Greek
(PDF/1.92 MB)
Hungarian
(PDF/1.9 MB)
Italian
(PDF/1.82 MB)
Latvian
(PDF/1.89 MB)
Lithuanian
(PDF/1.85 MB)
Maltese
(PDF/1.92 MB)
Polish
(PDF/1.9 MB)
Portuguese
(PDF/1.83 MB)
Romanian
(PDF/1.85 MB)
Slovak
(PDF/1.9 MB)
Slovenian
(PDF/1.89 MB)
Spanish
(PDF/1.83 MB)
Swedish
(PDF/1.83 MB)

Zynteglo Article-20 referral - Changes to the summary of product characteristics, labelling and package leaflet (PDF/1.42 MB)

First published: 23/07/2021

European Commission final decision

Zynteglo Article-20 referral - PRAC assessment report (PDF/1.19 MB)

Adopted

First published: 04/10/2021
EMA/418200/2021

Zynteglo Article-20 referral - Annex III (PDF/1.56 MB)

First published: 04/10/2021

Bulgarian
(PDF/1.94 MB)
Croatian
(PDF/2.32 MB)
Czech
(PDF/3.06 MB)
Danish
(PDF/2.28 MB)
Dutch
(PDF/2.3 MB)
Estonian
(PDF/2.27 MB)
Finnish
(PDF/2.3 MB)
French
(PDF/2.31 MB)
German
(PDF/2.32 MB)
Greek
(PDF/3.51 MB)
Hungarian
(PDF/360.51 KB)
Icelandic
(PDF/2.3 MB)
Italian
(PDF/2.31 MB)
Latvian
(PDF/3.16 MB)
Lithuanian
(PDF/2.36 MB)
Maltese
(PDF/3.04 MB)
Norwegian
(PDF/2.27 MB)
Polish
(PDF/3.1 MB)
Portuguese
(PDF/2.3 MB)
Romanian
(PDF/2.38 MB)
Slovak
(PDF/3.04 MB)
Slovenian
(PDF/2.97 MB)
Spanish
(PDF/2.3 MB)
Swedish
(PDF/2.28 MB)

Zynteglo Article-20 referral - Annex IV (PDF/707.77 KB)

First published: 04/10/2021

Bulgarian
(PDF/125.76 KB)
Croatian
(PDF/1.38 MB)
Czech
(PDF/1.91 MB)
Danish
(PDF/1.87 MB)
Dutch
(PDF/1.31 MB)
Estonian
(PDF/1.28 MB)
Finnish
(PDF/1.31 MB)
French
(PDF/1.29 MB)
German
(PDF/1.3 MB)
Greek
(PDF/2.18 MB)
Hungarian
(PDF/1.39 MB)
Italian
(PDF/1.3 MB)
Latvian
(PDF/1.4 MB)
Lithuanian
(PDF/1.35 MB)
Maltese
(PDF/1.41 MB)
Polish
(PDF/1.39 MB)
Portuguese
(PDF/1.32 MB)
Romanian
(PDF/1.34 MB)
Slovak
(PDF/1.38 MB)
Slovenian
(PDF/1.38 MB)
Spanish
(PDF/1.3 MB)
Swedish
(PDF/1.29 MB)

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

Overview - lay-language summary of the stage of the procedure
Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.

Zynteglo

Overview

CHMP endorses review finding no link between viral vector in Zynteglo and blood cancer

Zynteglo Article-20 referral - CHMP endorses review finding no link between viral vector in Zynteglo and blood cancer (PDF/1.25 MB)

Key facts

All documents

Procedure started

Zynteglo Article-20 referral - PRAC List of questions (PDF/796.86 KB)

Zynteglo Article-20 referral - Notification (PDF/278.35 KB)

Zynteglo Article-20 referral - Timetable for the procedure (PDF/683.15 KB)

Zynteglo Article-20 referral - Review of thalassaemia medicine Zynteglo started (PDF/701.84 KB)

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Zynteglo Article-20 referral - EMA finds no evidence linking viral vector in Zynteglo to blood cancer (PDF/702.81 KB)

Opinion provided by Committee for Medicinal Products for Human Use

Zynteglo Article-20 referral - CHMP endorses review finding no link between viral vector in Zynteglo and blood cancer (PDF/1.25 MB)

Zynteglo Article-20 referral - Changes to the summary of product characteristics, labelling and package leaflet (PDF/1.42 MB)

European Commission final decision

Zynteglo Article-20 referral - PRAC assessment report (PDF/1.19 MB)

Zynteglo Article-20 referral - Annex III (PDF/1.56 MB)

Zynteglo Article-20 referral - Annex IV (PDF/707.77 KB)

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