Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 13-16 December 2010

Review of benefits and risks of Avastin concluded

Finalising a review of Avastin (bevacizumab), from Roche Registration Ltd, the Committee confirmed that the benefits of Avastin in combination with paclitaxel outweigh its risks and that this combination remains a valuable treatment option for patients suffering from metastatic breast cancer.

The CHMP also concluded that Avastin in combination with docetaxel should no longer be used in the treatment of metastatic breast cancer. Patients who are currently being treated with this combination should discuss their ongoing treatment with their doctor.

Avastin is an anticancer medicine which contains the active substance bevacizumab. It is used in combination with other anticancer treatments to treat cancers of the colon, rectum, lung, kidney or breast. The CHMP's review was restricted to the use of Avastin in breast cancer and does not affect its use in the other indications.

Positive opinion for new medicines adopted

The Committee adopted positive opinions recommending the granting of marketing authorisations for the following new medicines:

• Esbriet (pirfenidone), an orphan medicine from InterMune Europe Ltd, intended for the treatment of idiopathic pulmonary fibrosis. The review for Esbriet began on 24 March 2010 with an active review time of 180 days.
• Orphacol (cholic acid), an orphan medicine from Laboratoires CTRS, intended for the treatment of inborn errors in primary bile acid synthesis due to 3β-hydroxy-Δ⁵-C₂₇-steroid oxidoreductase deficiency or Δ⁴-3-oxosteroid-5β-reductase deficiency. The review for Orphacol began on 18 November 2009 with an active review time of 210 days.
• Teysuno (tegafur/gimeracil/oteracil), an orphan medicine from Taiho Pharma Europe Ltd, intended for the treatment of advanced gastric cancer in adults when given in combination with cisplatin. The review for Teysuno began on 18 November 2009 with an active review time of 210 days.
• Xeplion (paliperidone) from Janssen-Cilag International N.V., for the treatment of schizophrenia. The review for Xeplion began on 3 December 2009 with an active review time of 180 days.
• Xiapex (collagenase clostridium histolyticum), from Pfizer Ltd, intended for the treatment of Dupuytren's contracture in adult patients with a palpable cord. The review for Xiapex began on 21 January 2010 with an active review time of 210 days.

Positive opinions for informed consent applications adopted

The Committee adopted positive opinions recommending the granting of marketing authorisations for the informed consent applications Daliresp and Libertek (roflumilast), from Nycomed GmbH, intended for the maintenance treatment of severe chronic obstructive pulmonary disease associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add-on to bronchodilator treatment. The reviews for Daliresp and Libertek began on 17 October 2010 with an active review time of 60 days. These applications were informed consent applications referring to the dossier of the authorised medicine Daxas.

Positive opinions for generic medicines adopted

The Committee adopted positive opinions recommending the granting of marketing authorisations for the following generic medicines:

• Ifirmacombi (irbesartan hydrochloride/hydrochlorothiazide), from Krka, d.d., Novo mesto, intended for the treatment of adult patients with essential hypertension, whose blood pressure is not adequately controlled with irbesartan or hydrochlorothiazide alone. Ifirmacombi is a generic of CoAprovel.
• Leflunomide Teva (leflunomide), from Teva Pharma B.V., intended for the treatment of adult patients with active rheumatoid arthritis. Leflunomide Teva is a generic of Arava.
• Repso (leflunomide), from Teva Pharma B.V., intended for the treatment of adult patients with active rheumatoid arthritis and active psoriatic arthritis. Repso is a generic of Arava.

Positive opinion for extension of therapeutic indications adopted

The Committee adopted a positive opinion for an application for extension of the therapeutic indications, adding a new treatment option for a medicine already authorised in the European Union (EU), for Simponi (golimumab), from Centocor B.V., to include adult patients with severe, active and progressive rheumatoid arthritis (RA) not previously treated with methotrexate and to include reduction in the rate of progression of joint damage in all RA populations.

Negative opinion for extension of therapeutic indications adopted

The Committee adopted a negative opinion for Avastin (bevacizumab), from Roche Registration Ltd, recommending that the current indication should not be extended to include first-line combination therapy with capecitabine in patients with metastatic breast cancer.

The review of benefits and risks of Avastin (see above) was triggered by data submitted in the context of this application.

Update on the withdrawal of Thelin

The Committee has reviewed the data on liver toxicity, including three cases of fatal liver injury, that had prompted the marketing authorisation holder, Pfizer, to withdraw the marketing authorisation for Thelin worldwide and to discontinue all ongoing clinical trials.

Review of the safety of somatropin-containing medicines started

The Committee has started a review of the safety of somatropin-containing medicines authorised centrally or by national procedures in the European Union. The CHMP will look into all available data on somatropin to reassess the benefit-risk balance of these medicines.

While this review is ongoing, the CHMP confirms that there is no immediate concern. However, prescribers are reminded to strictly follow the indications and the approved doses. The maximum recommended dose of 50µg/kg weight/day for somatropin-containing medicines should not be exceeded.

Review of potential presence of endotoxins in peritoneal dialysis solutions concluded

The Committee concluded a review on the potential presence of endotoxins in the peritoneal dialysis solutions Dianeal, Extraneal and Nutrineal, from Baxter. These are sterile solutions used in patients who have to undergo peritoneal dialysis because of kidney failure.

Although the number of batches affected is likely to be low, the CHMP concluded that current stocks should be replaced, because it is not possible to identify which bags are affected and there is a risk that patients who receive peritoneal solutions which contain endotoxins may develop aseptic peritonitis. The replacement of batches should be handled in such a way that vulnerable patients who rely on a particular type of solution are not put at risk. The CHMP has therefore recommended an action plan so that patients who are most in need continue to have access to treatment.

Arbitration concluded

The Committee completed an arbitration procedure initiated because of disagreement among EU Member States regarding the authorisation of the generic isotretinoin-containing medicine Isotretinoin Ranbaxy (UK) Limited, from Ranbaxy (UK) Ltd. This medicine is indicated for treatment of severe acne that has not responded to standard treatments.

This procedure was initiated because of concerns that bioequivalence of this medicine to the reference product Roaccutane had only been shown under fasting conditions but not under fed conditions, and that this could thus result in suboptimal dosing. The Committee concluded that bioequivalence with the reference product has not been shown according to current requirements and that the benefit-risk balance of this medicine is negative.

The CHMP therefore recommended that marketing authorisations should not be granted in the concerned Member States and it should be suspended in the United Kingdom where it is already authorised.

Harmonisation referral concluded

The Committee recommended harmonisation of the prescribing information for the medicine Tienam (imipenem/cilastatin), from Merck Sharp & Dohme and associated companies. This medicine is an antibiotic authorised to treat complicated intra-abdominal infections, severe pneumonia, intra- and post-partum infections, complicated urinary tract infections, complicated skin and soft-tissue infections and the treatment of bacteraemia associated with these infections.

This review was initiated because of differences in the summaries of product characteristics, labelling and package leaflets in the countries where the product is marketed.

Notes

• The review of Avastin was conducted under Article 20 of Regulation (EC) No 726/2004.
• The review of peritoneal dialysis solutions was conducted under Article 5(3) of Regulation (EC) No 726/2004, at the request of the UK Medicines and Healthcare products Regulatory Agency.
• The reviews of the centrally authorised somatropin-containing medicines NutropinAq, Omnitrope and Valtropin are being conducted under Article 20 of Regulation (EC) No 726/2004.T
• The review of nationally authorised somatropin-containing medicines is being conducted under Article 107 of Directive 2001/83/EC.
• The review of Isotretinoin Ranbaxy (UK) Limited was conducted under Article 29 of Directive 2001/83/EC.
• The harmonisation referral on Tienam was conducted under Article 30 of Directive 2001/83/EC, as amended.
• A more detailed CHMP meeting report will be published shortly.