The European Medicines Agency (EMA) has recommended label changes to Servier’s osteoporosis drugs Protelos and Osseor to include new contraindications and revised warnings.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that the drugs are an important treatment for women with osteoporosis, but that the associated risks need better management.

The CHMP no longer recommends Protelos and Osseor (strontium ranelate) for use in immobilised patients or patients with venous thromboembolism (VTE), and has recommended an update of the warnings regarding serious skin reactions.

Both drugs are indicated for the treatment of osteoporosis in postmenopausal women to reduce the risk of hip and spine fractures.

The review followed the publication of a French study that identified 199 severe adverse reactions to these medicines between January 2006 and March 2009. Around half were VTE events and around a quarter were skin reactions.

The risk of VTE was identified in clinical trials, and the risk of severe skin reactions had been reported from patient experience. These risks were already noted in the product information.

The CHMP has reviewed all available data on the safety of Protelos and Osseor and recommended:

• Doctors should not prescribe these drugs for patients with VTE or a history of VTE, or to patients who are immobilised. Patients in these categories should discuss their treatment with their doctor at their next scheduled appointment.

• Doctors should re-evaluate the need to continue treatment with Protelos or Osseor in patients over 80 years of age at risk of VTE.

• Prescribers should make patients aware of the time-to-onset and likely signs and symptoms of severe skin reactions. Patients should stop treatment immediately if such symptoms occur, and not resume at any time.

The European Medicines Agency (EMA) has recommended Nimenrix from GlaxoSmithKline (GSK) for active immunisation against a form of meningitis that is prevalent in Africa.

Nimenrix (MenACWY-TT) is a candidate conjugate vaccine against invasive meningococcal disease caused by the Neisseria meningitidis virus.

The positive recommendation improves the global prospect of controlling a highly contagious, disabling and sometimes fatal disease.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed 17 clinical studies from 17 countries, covering immunogenicity and safety data from more than 8,000 patients.

According to a recent WHO report, meningococcal disease can affect as many as one person in ten in a region of Africa that contains 300 million people. It is relatively rare in Europe, with incidence reaching 140 cases per million people.

Thomas Breuer, Senior VP and Head of Global Vaccine Development at GSK, said: GSK has over 20 years’ experience in developing meningococcal vaccines. This positive opinion represents a major milestone in our development programme.”

GSK’s vaccines business, GSK Biologicals, has over 30 vaccines currently approved for marketing and 20 more in development.

The EMA is to start publishing information on centralised marketing authorisation applications for medicines it has received for evaluation.

The move is part of the Agency’s drive to increase transparency on its and other European regulatory bodies’ activities.

From the start of March, it will begin to publish the international non-proprietary names (INN) and therapeutic areas for all new medicines under evaluation by the Committee for Medicinal Products for Human Use (CHMP).

Details on the type of salt, ester or derivative of the active substance in treatments will also be published. But where generics and biosimilar medicines are concerned, only the INN and therapeutic area will be released to the public.

The new initiative follows the EMA’s publication of data on designated orphan medicines that are being assessed for a marketing authorisation in its monthly reports. Currently, data on other types of medicines is not published by the Agency until the end of the assessment procedure.

The CHMP has issued a positive opinion for the use of Byetta (exenatide twice-daily) as an add-on therapy to basal insulin for the treatment of type 2 diabetes in adults who have not achieved adequate glycaemic control.

The treatment, to be used with or without metformin and/or Actos (pioglitazone), demonstrated in clinical trials that it can reduce glycaemic control levels.

Christian Weyer, Senior Vice President, R&D, Amylin Pharmaceuticals, says Byetta “has potential as a complementary treatment approach for several reasons”.

The double-blind, 30-week clinical trial evaluating Byetta as an add-on therapy to insulin glargine showed that patients who may have been at risk of hypoglycaemia reduced their glargine dosage by a fifth.

Then, five weeks after randomisation, all patients had insulin doses titrated to achieve target fasting glucose levels. After the full 30 weeks of treatment, Byetta demonstrated a statistically significant reduction in hypoglycaemia compared to placebo, lowering levels by 1.7% from a baseline of 8.3%.

“Byetta is given in a fixed-dose regimen,” said Christian Weyer. “Its effects contribute to improved glycaemic control after meals, complementing the control of fasting blood sugar achieved with basal insulin. And in a clinical study, patients using Byetta with insulin glargine achieved better glycaemic control, without weight gain or an increased risk of hypoglycaemia, than patients using insulin glargine without Byetta.”

The injection was the first glucagon-like peptide-1 (GLP-1) receptor agonist to be approved by the FDA for the treatment of type 2 diabetes.

In November last year, Amylin and Eli Lilly announced they had amicably terminated their decade-long collaboration on the treatment.

The European Medicines Agency (EMA) has recommended lifting the suspension of blood loss restricting medicine Trasylol (injectable aprotinin), denied EU marketing authorisation since 2008.

The review stated that the results of the BART study, on which the suspension was based, were unreliable and not supported by later studies.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that Trasylol’s benefits outweigh its risks in a more narrowly defined group of patients than before.

The review examined the benefits and risks of all antifibrinolytic drugs, which prevent excessive blood loss by helping to preserve blood clots.

Before its suspension in 2008, Bayer’s Trasylol was authorised in the EU for patients undergoing heart bypass surgery, reducing the risk of major bleeds.

The CHMP concluded that the drug has a positive benefit-risk balance in patients undergoing isolated heart bypass surgery who are at high risk of major blood loss.

Trasylol sales were suspended in May 2008 on the recommendation of the CHMP, following the preliminary results of the BART study with high-risk heart surgery patients, which appeared to show an increased death rate with Trasylol after 30 days relative to other medicines.

The current review compared the final results of the BART study with those of other clinical studies and wider research and clinical data. It concluded that the BART study did not take account of imbalances in the use of blood-thinning medicines such as heparin, and that its findings were not replicated in other studies.

The CHMP further recommended that doctors be warned of the importance of heparin, and that the use of Trasylol in the EU be monitored through a registry.

The EMA has granted conditional approval for Pixuvri (pixantrone dimaleate) – the first treatment for non- Hodgkin’s B-cell lymphoma in patients whose cancer has returned.

The CHMP recommended the use of the treatment in patients whose cancer is aggressive and has returned after multiple rounds of chemotherapy or is not responding to other treatments.

Pixuvri, the Committee says, satisfies an unmet medical need and the benefits of the medicine outweigh the risks despite the need for additional data in patients who have previously received MabThera (rituximab).

The initial main study demonstrated that Pixuvri’s benefits outweigh its risks. Data highlighted how a greater number of patients responded to the drug than a comparator chemotherapy, and that individuals receiving Pixuvri went an average of 10.3 months longer without their disease getting worse.

The Committee also noted that the benefit appeared to be lower in patients who had previously received MabThera and that its benefit was not established in patients when used as the fifth or later round of chemotherapy in those whose disease had not responded to treatment.

Pixuvri’s conditional approval will now continued to be monitored on an annual basis until the data on MabThera-pretreated patients has been conducted and presented. This information is expected in 2015.

The CHMP’s decision has now been sent to the European Commission for the adoption of an EU-wide decision.

Novartis will revise the product information for its hypertension drug Rasilez (aliskiren) to take account of new European Medicines Agency (EMA) drug interaction warnings.

A risk-benefit review from the EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that aliskiren-containing medicines may interact harmfully with ACE inhibitors or ARBs.

The CHMP review followed Novartis’ decision in December 2011 to abandon the ALTITUDE trial of Rasilez used in combination with those medications.

While confirming that Rasilez is suitable for the treatment of essential hypertension (where no external risk factors present), the CHMP requested two changes in the product information in the EU:

• A contraindication against its use with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in patients with diabetes and/or moderate to severe renal impairment.

• A warning against its use in any patients who are taking an ACE inhibitor or an ARB, asking the doctor to assess the balance of risk and benefit carefully.

Novartis will inform doctors in the EU of these changes, which will also affect combination products containing aliskiren such as Rasilamlo and Rasitrio.

David Epstein, Division Head of Novartis Pharmaceuticals, commented: “Patient safety continues to be the highest priority for Novartis, and we are working closely with the CHMP, EMA and other health authorities worldwide to continue to provide Rasilez and combination products containing aliskiren to the most appropriate patient population who would benefit.”

The ALTITUDE study was a large-scale trial of Rasilez used in combination with an ACE inhibitor or ARB in a specific population of patients with type 2 diabetes and renal impairment to reduce the risk of cardiovascular and renal events.

Novartis halted the trial in December after the Data Monitoring Committee concluded from preliminary interim data that the combination in these patients not only did not reduce the risk of such events, but actually increased it.

The company warned doctors worldwide not to prescribe aliskiren-containing products to patients with diabetes who were receiving an ACE inhibitor or ARB. This warning remains in place outside the EU pending further discussions.

Rasilez (Tekturna in the US) was approved in the EU and the US in 2007 for treatment of hypertension as a monotherapy or in combination with other drugs. It is available in tablet form in all EU Member States except Estonia, Latvia, Lithuania and Romania.

Novartis Vaccines and Diagnostics S.r.l. has formally notified the EMA of its intention to withdraw the paediatric-use marketing authorisation (PUMA) for Fluad Paediatric (influenza vaccine, surface antigen, inactivated, adjuvanted with MF59C.1).

The EMA was informed in an official letter that Novartis were unable to address the questions raised by the Committee for Medicinal Products for Human Use (CHMP) within the required timelines.

The European healthcare regulator said the withdrawal does not prejudice the possibility of Novartis making a new application at a later stage.

Fluad Paediatric was intended to be used for the active immunisation against influenza in infants and young children. Its initial application was submitted to the EMA in December 2010. At the time of the withdrawal, it was under evaluation by the CHMP.

The European Commission (EC) has requested further information in order to reach a decision on whether to give marketing approval to Glybera, a gene-based drug for the rare genetic disorder lipoprotein lipase deficiency (LPLD).

Glybera (alipogene tiparvovec) from Amsterdam Molecular Therapeutics (AMT) was recommended for marketing approval by the Committee for Advanced Therapies (CAT), an expert body that advises the European Medicines Agency (EMA) on gene therapies and other advanced biopharmaceuticals.

However, the EMA’s Committee for Human Medicinal Products (CHMP) recently recommended that Glybera should be denied marketing approval – a conflict of views that has led the EC to request that the CHMP acquire further data.

LPLD is a currently untreatable orphan disease (by EU definition, affecting fewer than five in 10,000 people) that causes inability to metabolise lipids, leading to recurrent and severe pancreatitis.

The negative CHMP opinion on Glybera led AMT to scale down its business plans, reducing its workforce by half. The announced delay in the EC judgement therefore has major potential implications for the company.

“We are very encouraged by the outcome of the discussion by the European Parliament's Standing Committee to request further information from the CHMP,” said Jorn Aldag, CEO of AMT. “The evaluation of (ultra-) orphan drugs and advanced therapies is novel territory. The ongoing debate shows that the authorities are determined to find the best process of dealing with such innovative treatments and technologies.

“We will constructively work with the European Commission and the EMA to find the best process going forward, not only for Glybera but also for further advanced therapies on their way to patients.”

AMT is a leading supplier of gene-based therapies. Its proprietary drug development platform addresses orphan diseases caused by a single faulty gene. Its product pipeline includes drugs for haemophilia B, Duchenne muscular dystrophy and Parkinson’s disease.

Novartis’ Signifor (pasireotide) has been recommended for approval by the CHMP for the rare hormonal disorder Cushing’s disease.

The somatostatin analogue would become the first approved medical therapy for the condition after it met the primary endpoint of normalising urinary-free cortisol (UFC) levels in a Phase III trial.

Hervé Hoppenot, President, Novartis Oncology, says the company is now “one step closer to being able to offer patients in Europe” a medical treatment.

Cushing’s disease is a debilitating and fatal disease which affects approximately one to two patients per million, per year. There are believed to be around a total of 20,000 people in Europe with the disease.

First-line therapy is the surgical removal of the tumour of the pituitary that produces too much adrenocorticotrophin (ACTH) and stimulates the adrenal glands to both grow and release excessive amounts of cortisol in to the blood. Symptoms include weight gain, bruising and high blood pressure.

Signifor has been designated as an orphan medicine since October 2009. In the Phase III PASPORT-CUSHINGS (PASireotide clinical trial PORTfolio - CUSHING'S disease) trial, the largest randomised study to evaluate a medical therapy in patients with the disease, it was shown to reduce levels of cortisol in urine by more than half in 41% of patients treated with a 900μg dose, and in more than a third of patients treated with a 600μg dose.

The European Commission will now decide whether to adopt the positive opinion of the CHMP. A decision is expected within the next three months and will apply to all 27 EU member states, plus Iceland and Norway.