Holoclar

ex vivo expanded autologous human corneal epithelial cells containing stem cells

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This is a summary of the European public assessment report (EPAR) for Holoclar. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Holoclar.

For practical information about using Holoclar, patients should read the package leaflet or contact their doctor or pharmacist.

What is Holoclar and what is it used for?

Holoclar is a stem-cell treatment used in the eye to replace damaged cells on surface (epithelium) of the cornea, the transparent layer in front of the eye covering the iris (the coloured part).

It is used in adult patients with moderate to severe limbal stem-cell deficiency caused by burns, including chemical burns, to the eyes. Patients with this condition do not have enough limbal stem cells which normally act as a regeneration system, replenishing the outer corneal cells when they get damaged and when they age.

Holoclar is a type of advanced therapy product called a ‘tissue engineered product’. It consists of cells taken from the patient’s limbus (at the edge of the cornea) and then grown in a laboratory so that they can be used to repair the damaged corneal surface.

Because the number of patients with limbal stem-cell deficiency due to burns to the eyes is low, the disease is considered ‘rare’, and Holoclar was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 7 November 2008.

How is Holoclar used?

Holoclar must only be used by an appropriately trained and qualified eye surgeon in a hospital, and must only be given to the patient whose limbal cells were used to manufacture the medicine.

In the first stage of treatment, a small part of healthy limbal tissue (1-2 mm2 in size) is taken from the patient in hospital and sent to the manufacturer on the same day. Next, the cells in the tissue are grown in a laboratory and frozen until the date of surgery is confirmed. Thawed cells are used to make Holoclar by growing them on a membrane made of a protein called fibrin. Holoclar, comprising the cells and the membrane, is then sent back to the hospital, where it is immediately surgically implanted in the patient’s eye.

Antibiotics to prevent eye infection should be given to patients after limbal tissue has been taken from them. Following the surgery, the patient should receive antibiotics and an appropriate anti-inflammatory medicine.

Holoclar is intended for a single treatment, although treatment can be repeated if the doctor considers it necessary. For further information, see the summary of product characteristics (also part of the EPAR).

How does Holoclar work?

The active substance in Holoclar is the patient’s own limbal cells, which include cells from the surface of the cornea and limbal stem cells grown in a laboratory. Before Holoclar is used, the damaged corneal surface tissue of the affected eye is removed. Once implanted in the eye, the corneal cells of Holoclar help to replace the corneal surface, while the limbal stem cells serve as a reservoir of new cells that continuously replenish the cornea.

What benefits of Holoclar have been shown in studies?

Holoclar was shown to be effective in restoring a stable corneal surface in patients with moderate or severe limbal stem-cell deficiency caused by burns in a retrospective study using patients’ past medical records. One year after Holoclar implantation, 75 out of 104 patients studied (72%) were judged to have had successful implants based on the presence of stable corneal surface with no surface defects and little or no ingrown blood vessels (a common feature of limbal stem-cell deficiency). There were also reductions in patients’ symptoms, such as pain and inflammation, and improvements in vision.

What are the risks associated with Holoclar?

The most common side effect with Holoclar (seen in more than 1 patient in 10) is blepharitis (inflammation of the eye lid). For the full list of all side effects and restrictions, see the package leaflet.

Why is Holoclar approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that Holoclar treatment was effective in restoring healthy corneal surfaces in patients with moderate or severe limbal stem-cell deficiency caused by burns as well as in improving their symptoms and vision. The Committee noted that that moderate to severe forms of limbal stem-cell deficiency are serious conditions which, if untreated, can lead to severe reduction or complete loss of vision. As the side effects of Holoclar treatment are generally manageable, the CHMP concluded that Holoclar’s benefits outweigh its risks and recommended that it be approved for use in the EU.

The conclusion on the benefit-risk balance of Holoclar is based on results of two retrospective studies (using past medical records), and the company is to provide further data from a prospective study (that records outcomes during the course of the study).

Holoclar has therefore been given ‘conditional approval’. This means that there is more evidence to come about the medicine, which the company is required to provide. Every year, the European Medicines Agency will review any new information that becomes available and this summary will be updated as necessary.

What information is still awaited for Holoclar?

Since Holoclar has been granted a conditional approval, the company that markets Holoclar will provide further data on Holoclar. The company is to provide data on the benefits and risks of Holoclar from a prospective clinical study.

What measures are being taken to ensure the safe and effective use of Holoclar?

A risk management plan has been developed to ensure that Holoclar is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Holoclar, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that makes Holoclar will provide healthcare professionals with educational material on the safe use of this treatment, including on the selection and follow-up of patients and on reporting side effects. Educational material will also be provided to patients undergoing treatment.

Further information can be found in the summary of the risk management plan.

Other information about Holoclar

The European Commission granted a marketing authorisation valid throughout the European Union for Holoclar on 17 February 2015.

For more information about treatment with Holoclar, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

Name Language First published Last updated
Holoclar : EPAR - Summary for the public BG = bălgarski 2015-03-02  
Holoclar : EPAR - Summary for the public ES = español 2015-03-02  
Holoclar : EPAR - Summary for the public CS = čeština 2015-03-02  
Holoclar : EPAR - Summary for the public DA = dansk 2015-03-02  
Holoclar : EPAR - Summary for the public DE = Deutsch 2015-03-02  
Holoclar : EPAR - Summary for the public ET = eesti keel 2015-03-02  
Holoclar : EPAR - Summary for the public EL = elliniká 2015-03-02  
Holoclar : EPAR - Summary for the public EN = English 2015-03-02  
Holoclar : EPAR - Summary for the public FR = français 2015-03-02  
Holoclar : EPAR - Summary for the public IT = italiano 2015-03-02  
Holoclar : EPAR - Summary for the public LV = latviešu valoda 2015-03-02  
Holoclar : EPAR - Summary for the public LT = lietuvių kalba 2015-03-02  
Holoclar : EPAR - Summary for the public HU = magyar 2015-03-02  
Holoclar : EPAR - Summary for the public MT = Malti 2015-03-02  
Holoclar : EPAR - Summary for the public NL = Nederlands 2015-03-02  
Holoclar : EPAR - Summary for the public PL = polski 2015-03-02  
Holoclar : EPAR - Summary for the public PT = português 2015-03-02  
Holoclar : EPAR - Summary for the public RO = română 2015-03-02  
Holoclar : EPAR - Summary for the public SK = slovenčina 2015-03-02  
Holoclar : EPAR - Summary for the public SL = slovenščina 2015-03-02  
Holoclar : EPAR - Summary for the public FI = suomi 2015-03-02  
Holoclar : EPAR - Summary for the public SV = svenska 2015-03-02  
Holoclar : EPAR - Summary for the public HR = Hrvatski 2015-03-02  
Name Language First published Last updated
Holoclar : EPAR - Risk-management-plan summary (English only) 2015-03-02  

This EPAR was last updated on 06/06/2016 .

Authorisation details

Product details

Product details for Holoclar
NameHoloclar
Agency product numberEMEA/H/C/002450
Active substance

ex vivo expanded autologous human corneal epithelial cells containing stem cells

International non-proprietary name (INN) or common name

ex vivo expanded autologous human corneal epithelial cells containing stem cells

Therapeutic area Corneal DiseasesStem Cell Transplantation
Anatomical therapeutic chemical (ATC) code S01XA19
Additional monitoring

This medicine is under additional monitoring. This means that it is being monitored even more intensively than other medicines. For more information, see medicines under additional monitoring.

Treatment of rare diseases

This medicine has an "orphan designation" which means that it is used to treat life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the European Union, or are medicines which, for economic reasons, would be unlikely to be developed without incentives.

Conditional Approval

Sometimes, the CHMP recommends that a medicine be given ‘conditional approval’. This happens when the Committee has based its positive opinion on data which, while not yet comprehensive, indicate that the medicine’s benefits outweigh its risks.

The company is given obligations to fulfil, such as the performance of further studies. The approval is renewed on a yearly basis until all obligations have been fulfilled, and is then converted from a conditional approval into a normal approval. Conditional approvals can only be granted for medicines that satisfy an ‘unmet medical need’, meaning the medicine is intended to be used for a disease or condition for which no treatment is readily available, and it is therefore important that patients have early access to the medicine concerned.

Publication details

Publication details for Holoclar
Marketing-authorisation holder

Chiesi Farmaceutici S.p.A.

Revision1
Date of issue of marketing authorisation valid throughout the European Union17/02/2015

Contact address:

Via Palermo 26/A 
43122 Parma 
Italy

Product information

Product information

10/12/2015  Holoclar -EMEA/H/C/002450 -R/0001

Name Language First published Last updated
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06
Holoclar : EPAR - Product Information EN = English 2015-03-02 2016-06-06

Contents

  • Annex I - Summary of product characteristics
  • Annex IIA - Manufacturing-authorisation holder responsible for batch release
  • Annex IIB - Conditions of the marketing authorisation
  • Annex IIIA - Labelling
  • Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.


Name Language First published Last updated
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  
Holoclar : EPAR - All Authorised presentations EN = English 2015-03-02  

Pharmacotherapeutic group

Ophthalmologicals

Therapeutic indication

Treatment of adult patients with moderate to severe limbal stem cell deficiency (defined by the presence of superficial corneal neovascularisation in at least two corneal quadrants, with central corneal involvement, and severely impaired visual acuity), unilateral or bilateral, due to physical or chemical ocular burns. A minimum of 1-2 mm2 of undamaged limbus is required for biopsy.

Assessment History

Changes since initial authorisation of medicine

Name Language First published Last updated
Holoclar : EPAR - Procedural steps taken and scientific information after authorisation EN = English 2016-06-06  

Initial marketing-authorisation documents

Name Language First published Last updated
Holoclar : EPAR - Public assessment report EN = English 2015-03-02  
CHMP summary of positive opinion for Holoclar EN = English 2014-12-19