Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - roctavian

Document Subject

Generated Narrative: MedicinalProductDefinition mp6154ec9930909dd76813cd26c37e2a8e

identifier: http://ema.europa.eu/identifier/EU/1/22/1668/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: ROCTAVIAN 2 × 1013 vector genomes/mL solution for infusion

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-6154ec9930909dd76813cd26c37e2a8e

identifier: http://ema.europa.eu/identifier/EU/1/22/1668/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - roctavian

Attesters

What is in this leaflet

1. What ROCTAVIAN is and what it is used for
2. What you need to know before you are given ROCTAVIAN
3. How ROCTAVIAN is given
4. Possible side effects
5. How ROCTAVIAN is stored
6. Contents of the pack and other information

What ROCTAVIAN is ROCTAVIAN is a gene therapy product that contains the active substance valoctocogene roxaparvovec. A gene therapy product works by delivering a gene into the body to correct a genetic deficiency.

What ROCTAVIAN is used for This medicine is used for the treatment of severe haemophilia A in adults who do not have current or past inhibitors to factor VIII and who do not have antibodies to the virus vector AAV5. Haemophilia A is a condition where people inherit an altered form of a gene needed to make factor VIII, an essential protein required for blood to clot and stop any bleeding. People with haemophilia A cannot produce factor VIII and are prone to internal or external bleeding episodes.

How does ROCTAVIAN work The active substance in ROCTAVIAN is based on a virus which does not cause disease in humans. This virus has been modified so that it cannot spread in the body but can deliver a working copy of the factor VIII gene into liver cells. This enables liver cells to produce factor VIII protein and raise levels of working factor VIII in the blood. In turn, this helps the blood to clot more normally and prevents bleeding or reduces bleeding episodes.

You will not be given ROCTAVIAN

• if you are allergic to valoctocogene roxaparvovec or any of the other ingredients of this medicine (listed in section 6).
• if you have an active infection or if you have a chronic (long-term) infection that is not controlled by medicines you take, or if you have scarring of the liver (significant liver fibrosis or cirrhosis), as this could affect your body s initial response to ROCTAVIAN.
• if you have antibodies to the type of virus used to make this medicine. Your doctor will test you beforehand to see if this is the case.

If any of the above applies to you, or if you are unsure of any of the above, please talk to your doctor before you receive ROCTAVIAN.

Warnings and precautions

Importance of liver health

• Your liver is the organ that produces factor VIII after treatment with ROCTAVIAN. You should take care of your liver s health so that it is functioning as optimally as possible and you can produce factor VIII and continue to produce factor VIII on an ongoing basis.
• Talk to your doctor about what you can do to improve and maintain your liver s health (see also You will not be given ROCTAVIAN, above, and Other medicines and ROCTAVIAN and ROCTAVIAN with alcohol, below).
• Your doctor may advise you against treatment with ROCTAVIAN if you have a liver disease that may prevent ROCTAVIAN from working well.

You may need to take an additional medicine

• You may need to take another medicine (corticosteroids) for an extended period of time (2 months or longer) after being given ROCTAVIAN to manage problems with your liver seen in tests. Corticosteroids may cause side effects while you receive them. Your doctor may advise you to avoid or postpone treatment with ROCTAVIAN if you are not able to safely receive corticosteroids and may also advise you of steps you should take for safe use or may give you an alternative medicine. See also section 3. Side effects during or shortly after ROCTAVIAN infusion
• Infusion-related side effects can occur during or shortly after you are given the ROCTAVIAN infusion (drip). Symptoms of such side effects are listed in section 4. Possible side effects. Tell your doctor or nurse immediately if you experience these or any other symptoms during or shortly after the infusion. Depending on your symptoms, your infusion may be slowed down or temporarily stopped, or you may be given medicines to treat them. Before you are discharged, your doctor will provide you with information on what to do in case you experience new side effects or side effects which come back once you leave the medical facility.

Possibility of unwanted blood clots when factor VIII levels improve

• After treatment with ROCTAVIAN, your factor VIII protein level may increase. In some patients, it may increase to levels above the normal range for a period of time.

Factor VIII is the protein necessary to form stable clots in your blood. Depending on your individual risk factors, an improvement in factor VIII levels may mean an increased possibility of unwanted blood clots (so called thromboses , in either veins or arteries). Discuss with your doctor your general risk factors for unwanted clots and for cardiovascular disease, and what to do about them. Also ask how to recognise symptoms of unwanted clots and what to do if you think you may have one.

Avoiding blood donations and donations for transplantations

• Do not donate blood, organs, tissues, or cells for transplant.

Immunocompromised patients or patients receiving immunosuppressive treatment

• If you are immunocompromised (when your immune system s ability to fight infections is reduced) or receiving immunosuppressive treatment, contact your doctor before starting treatment with ROCTAVIAN. You may need to be monitored more closely if your immune system is not working properly to ensure you can receive treatment and other medicines such as corticosteroids or if you need to change your existing medicines.

Receiving gene therapy again in the future

• After receiving ROCTAVIAN, your immune system will produce antibodies to the shell of the AAV vector. It is not yet known whether or under which conditions therapy with ROCTAVIAN may be repeated. It is also not yet known whether or under which conditions subsequent use of another gene therapy may be possible.

Use of other haemophilia treatments

• After ROCTAVIAN use, talk to your doctor about if or when you should stop your other haemophilia treatments and develop a treatment plan of what to do in case of surgery, trauma, bleeds, or any procedures that could potentially increase the risk of bleeding. It is very important to continue your monitoring and doctor visits to determine if you need to take other treatments to manage haemophilia.

Monitoring tests Before treatment with ROCTAVIAN, your doctor will perform tests to assess your liver health.

After treatment with ROCTAVIAN blood tests will be done to check:

• when your liver starts producing factor VIII so you know when you can stop your regular treatment with factor VIII products,
• how much factor VIII your liver produces on an ongoing basis,
• how your liver cells react to the treatment with ROCTAVIAN, and
• whether you develop inhibitors (neutralising antibodies) to factor VIII.

How often blood tests have to be done depends on how you react to ROCTAVIAN. In general, during the first 26 weeks after treatment, blood tests will be done every week, then every 2 to 4 weeks until the end of the first year. After the first year, blood tests will be done less frequently as advised by your doctor. It is important that you discuss the schedule for these blood tests with your doctor so that they can be carried out as necessary.

Because not all patients will respond to ROCTAVIAN and the reasons for this have not been established, your doctor will not be able to predict whether you will respond fully to the treatment. There is the potential that you may not benefit from ROCTAVIAN while still be exposed to long-term risks.

If you respond to the treatment, it is unknown how long the treatment will last. A positive treatment effect of up to five years has been reported in some patients.

There are no plans to administer the medicine a second time for patients who do not respond or have lost the response.

Long-term follow-up tests may be required to verify a continued safe and effective response to ROCTAVIAN.

Risk of malignancy potentially associated with ROCTAVIAN

• ROCTAVIAN can insert into liver cell DNA and there is the possibility that it can also insert into DNA of other body cells. As a consequence, ROCTAVIAN could contribute to a risk of cancer. Although there is no evidence of this in the clinical trials so far, this remains possible because of the nature of the medicine. You should therefore discuss this with your physician. After treatment with ROCTAVIAN, you will be recommended to enrol in a registry to help study the long-term safety of the treatment for 15 years, how well it continues to work and any side effects that may be linked to the treatment. In the event of cancer, your doctor may take a sample for further evaluation.

Children and adolescents ROCTAVIAN is for use in adults only. ROCTAVIAN has not yet been tested for use in children or adolescents.

Other medicines and ROCTAVIAN Before and after treatment with ROCTAVIAN, tell your doctor if you are using, have recently used or plan to use any other medicines, including herbal products or nutritional supplements. This is to make sure you avoid, as far as possible, taking anything that could damage your liver or impact the response to corticosteroids or ROCTAVIAN (such as isotretinoin, a medicine which is used to treat acne) or some medicines for the treatment of HIV (see section above on Immunocompromised patients or patients receiving immunosuppressive treatment). This is especially important during the first year after ROCTAVIAN treatment (see also Warnings and precautions).

As corticosteroids can affect the body s immune (defence) system, your doctor may adjust the timing of vaccinations and may recommend you do not receive certain vaccinations while on corticosteroid treatment. Talk to your doctor if you have any questions.

ROCTAVIAN with alcohol Drinking alcohol could affect your liver s ability to produce factor VIII after treatment with ROCTAVIAN. You should avoid alcohol for at least one year after treatment. Talk to your doctor about how much alcohol may be acceptable for you after the first year (see also Warnings and precautions).

Pregnancy, breast-feeding and fertility ROCTAVIAN is not recommended in women who are able to become pregnant. It is not yet known whether ROCTAVIAN can be used safely in these patients as the effects on pregnancy and the unborn child are not known. It is also not known whether ROCTAVIAN passes into breast milk.

There is no information on the effect of ROCTAVIAN on male or female fertility.

Use of contraception and avoiding partner pregnancy for a period of time

• After a male patient has been treated with ROCTAVIAN, the patient and any female partner must avoid pregnancy for 6 months. You should use effective contraception (e.g., double-barrier contraception such as condom and diaphragm). This is to prevent the theoretical risk that the factor VIII gene from a father s ROCTAVIAN treatment is transmitted to a child with unknown consequences. For the same reason, male patients must not donate semen for 6 months. Discuss with your doctor which methods of contraception are suitable.

Driving and using machines Temporary light-headedness (near-fainting), dizziness, tiredness, and headaches were observed after ROCTAVIAN infusion. If you are affected, you should use caution until you are certain that ROCTAVIAN does not adversely affect your ability to drive or use machines. Talk to your doctor about this.

ROCTAVIAN contains sodium This medicine contains 29 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.5% of the recommended maximum daily dietary intake of sodium for an adult. The amount of sodium you will receive depends on the number of ROCTAVIAN vials used for your infusion.

ROCTAVIAN will be given by a doctor who specialises in the management of your condition.

The doctor will work out the correct dose for you, based on your body weight.

Treatment with ROCTAVIAN consists of one single infusion (drip) into a vein. The infusion may take several hours to be completed.

The infusion will be given to you in a medical facility. During and after the infusion, you will be observed to detect possible side effects.

You will be allowed to go home (usually later the same day) once it has been decided that further observation is not necessary.

Additional medicine you may need

You may need to take another medicine (corticosteroids) for an extended period of time (for example, 2 months or longer) after ROCTAVIAN treatment to improve your response to therapy. It is important that you take this additional medicine according to the instructions given. You should read the package leaflet for any additional medicine you are prescribed and discuss with your doctor the possible side effects and any monitoring that may be needed.

If you are given more ROCTAVIAN than you should be As this medicine is given in hospital, and the dose is worked out and checked by your medical team, it is unlikely that you will be given too much. If you are given too much ROCTAVIAN, you might have higher factor VIII levels than needed, which may theoretically increase the possibility of unwanted blood clots. If this occurs, your doctor will treat you as necessary.

If you have any further questions on the use of this medicine, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Infusion-related side effects can occur during or shortly after your infusion (commonly; may affect up to 1 in 10 people). Tell your doctor or nurse immediately if you experience any of the following symptoms or any other symptoms during or shortly after the infusion:

• Hives or other rashes, itching
• Difficulty breathing, sneezing, coughing, runny nose, watery eyes, tingling throat
• Nausea (feeling sick), diarrhoea
• High or low blood pressure, rapid heartbeat, light-headedness (near-fainting)
• Muscle pain, back pain
• Fever, chills, shivering

Such symptoms can occur alone or in combination. Depending on your symptoms, your infusion may be slowed down or temporarily stopped, or you may be given medicines to treat them. Before discharging you, your doctor will provide you with information on what to do in case you experience a new or recurring side effect once you leave the medical facility.

Increased levels of liver proteins occurred after ROCTAVIAN infusion. In some cases, these increases occurred together with a decrease in factor VIII levels. Increases in the levels of liver proteins seen in blood tests can be the reason to start treatment with a corticosteroid.

The following side effects may happen with ROCTAVIAN. Some of these side effects can occur during or shortly after infusion.

Very common (may affect more than 1 in 10 people)

• Increased levels of liver proteins seen in blood tests
• Nausea (feeling sick)
• Headache
• Factor VIII above normal levels
• Tiredness
• Diarrhoea
• Abdominal (belly) pain
• Vomiting
• Increased levels of creatine phosphokinase (CPK) protein (an enzyme released into the blood when muscle is damaged) seen in blood tests

Common (may affect up to 1 in 10 people)

• Rash (including hives or other forms of rash)
• Heartburn (dyspepsia)
• Muscle pain
• Flu-like symptoms
• Dizziness
• Itching
• Increased blood pressure
• Allergic reaction

Uncommon (may affect up to 1 in 100 people)

• Light-headedness (near-fainting)
• Difficulty breathing

Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep this medicine out of the sight and reach of children.

This medicine must not be used after the expiry date which is stated on the carton and vial after EXP . The expiry date refers to the last day of that month.

ROCTAVIAN will be stored by the healthcare professionals at your healthcare facility. It must be stored upright and in its original carton (in order to protect it from light).

It must be stored and transported frozen at or below -60 C. Once thawed, it must be used within 10 hours at 25 C (this includes hold time in the vial and syringe, and time for infusion) or discarded. If needed, an intact vial (stopper not yet punctured) that has been thawed can be stored refrigerated (2 to 8 C) for up to 3 days, upright and protected from light (e.g., in the original carton).

Thawed ROCTAVIAN must not be used if the solution is not clear and colourless to pale yellow.

What ROCTAVIAN contains

• The active substance is valoctocogene roxaparvovec.
• The other ingredients are; disodium phosphate dodecahydrate (E339), mannitol (E421), poloxamer 188, sodium chloride, sodium dihydrogen phosphate dihydrate (E339), and water for injections. See end of section 2 ROCTAVIAN contains sodium for information on the total sodium content. This medicine contains genetically modified organisms (GMOs).

What ROCTAVIAN looks like and contents of the pack When thawed, ROCTAVIAN is a clear, colourless to pale yellow solution for infusion. It is supplied in a vial.

Pack size: 1 vial of 8 mL

Marketing Authorisation Holder and Manufacturer BioMarin International Ltd. Shanbally, Ringaskiddy County Cork P43 RIreland

This leaflet was last revised in

This medicine has been given conditional approval . This means that there is more evidence to come about this medicine. The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: