Alipogene tiparvovec

Very limited data on pregnancies exposed to alipogene tiparvovec is available. Animal studies do not indicate any harmful effects on pregnancy or embryonal/foetal development from alipogene tiparvovec. Alipogene tiparvovec should not be administered to pregnant women unless the possible benefit to the mother outweighs the possible risk to the foetus.

It is not known whether alipogene tiparvovec is excreted in human milk. Alipogene tiparvovec should not be administered to women who are breast-feeding as long as breastfeeding is ongoing.

Fertility

No clinical data on the effect of alipogene tiparvovec on fertility are available. Effects on male and female fertility have not been evaluated in animal studies.

Contraception in males and females

Women of childbearing potential must be advised to use reliable barrier contraception methods in accordance with the guidelines for immunosuppressants for a minimum of 12 months from the start of therapy (9 months following cessation of immunosuppressants). Therefore, use of barrier contraception methods for at least 12 months following alipogene tiparvovec administration is recommended.

Oral contraceptive use is contraindicated in LPLD patients as this may exacerbate the underlying disease.

Male patients, including vasectomised males, are advised to practise barrier contraception methods for at least 12 months following alipogene tiparvovec administration.

Alipogene tiparvovec has minor influence on the ability to drive and use machines¸ dizziness was commonly observed after alipogene tiparvovec administration. Patients experiencing dizziness are advised to not drive or use machines.

Summary of the safety profile

The most commonly reported adverse reaction is pain in extremity occurring in approximately one third of patients. One patient was diagnosed with pulmonary embolism 7 weeks after therapy. Given the small patient population and size of the cohorts, captured adverse reactions and serious adverse reactions do not provide a complete perspective on the nature and frequency of these events.

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA body system organ class and by frequency. Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Immunogenicity

An immune response was seen despite the use of immunosuppressants. In clinical trials with alipogene tiparvovec, antibodies against the adeno-associated virus (AAV) protein shell were present prior to treatment, in 18 out of 27 subjects; anti-AAV antibodies appeared or increased after alipogene tiparvovec administration, in all of the subjects. The clinical relevance of the antibody response is unknown. No neutralising assay was used.

T-cell responses against AAV were detected in approximately half of the subjects post therapy only. No T-cell response to LPL was detected in any subject.

With the exception of a case of fever (39.9°C) in study CT-AMT-011-01 which reversed within a day, no alipogene tiparvovec or immunosuppression related serious adverse events occurred.