The FDA has said that MS drug Gilenya (fingolimod) should not be used in patients with a recent history of stroke or heart disease.

The requested label change adds to changes requested by the EMA and the FDA in April to reduce the risk of cardiovascular and neurovascular events.

The FDA also concluded that a number of sudden deaths in patients with severe MS taking Gilenya could not be conclusively linked to the drug.

Gilenya was recommended by NICE in late April as a “valuable new therapy” for severe relapsing-remitting MS.

The new FDA safety review reinforced the earlier recommendation that doctors monitor the heart rate of patients taking Gilenya for the first time.

However, it said that the death of a 59-year-old patient in November after a first dose of Gilenya could have been caused by the patient’s advanced brainstem MS lesions and not by the drug.

In other cases of sudden death in patients taking Gilenya, it said, the drug’s “contribution to the death was unclear”.

However, the FDA definitely recommended not using Gilenya in patients who have suffered a stroke or heart disease within the previous six months, or who are taking certain medications for cardiac arrhythmia.

Gilenya was approved in the US in 2010 and in the EU in 2011, and remains the only oral MS drug on the market.

Gilenya (fingolimod) has become the first pill-based treatment for highly active relapsing-remitting multiple sclerosis (RRMS) recommended on the NHS after being backed in final guidance by NICE.

NICE had originally failed to recommend the pill in draft guidance but reconsidered its decision after Novartis and clinicians provided additional information and analysis on the effectiveness of the medication.

Professor Carole Longson, Director of the Health Technology Evaluation Centre at NICE, says the convenient treatment “is a valuable new therapy” for patients with RRMS.

RRMS is estimated to affect around 27,500 people in England and Wales and is the most common type of multiple sclerosis. Treatments to manage relapses are usually administered by injection.

NICE now specifically recommends the “innovative” treatment for adults who have an unchanged or increased relapse rate or ongoing severe relapses compared to the previous year, despite treatment.

But NICE states the recommendation only applies if Novartis provides Gilenya under the proposed terms in its confidential Patient Access Scheme it agreed with the DH.

“We are pleased to recommend fingolimod as a treatment option for the specific patient population for whom it has been demonstrated to be cost effective, providing Novartis applies its proposed discount,” said Professor Longson. “Multiple sclerosis can be a disabling condition and so we hope that this novel treatment will help to reduce relapses for these people.”

The treatment recently had its label updated to include new prescribing guidelines after the EMA and FDA raised concerns over cardiovascular events in certain patients.

Multiple sclerosis (MS) treatment Gilenya (fingolimod) has had its prescribing information updated after discussions with the EMA and the FDA.

Novartis has agreed to the updates to provide healthcare professionals with further guidance on initiating its use in patients with MS after reviews by both health regulators following cardiovascular concerns in certain patients.

Patients starting the use of Gilenya should have an electrocardiogram (ECG) and blood pressure measurement prior to the first dose with regular updates and continuous ECG monitoring for a minimum of six hours afterwards.

The CHMP has now confirmed a positive benefit-risk profile for the once-daily oral medication following the label change.

“We believe that Gilenya is a valuable treatment option for many patients with relapsing-remitting MS, and we welcome the confirmation of the positive benefit-risk profile of the drug which also supports our continued belief of the blockbuster potential of Gilenya,” said David Epstein, Division Head of Novartis Pharmaceuticals.

In additional, the label update in the EU also cautions against Gilenya’s use in patients who may be less tolerant of it or are more likely to develop a significantly slowed or abnormal heart rate because of certain underlying conditions or concomitant medications.

In the EU, Gileyna is approved for people with highly active relapsing-remitting MS despite treatment with beta interferon, or in patients with rapidly evolving severe relapsing-remitting MS.

The CHMP’s labelling recommendations will be reviewed by the European Commission with a final decision expected in June 2012.

NICE has reversed its original decision on Novartis’ Gilenya (fingolimod), the first pill to treat multiple sclerosis, in final draft guidance.

Gilenya is now recommended after NICE assessed a public consultation which Novartis and clinicians provided additional information and analysis on the effectiveness of the medication.

Sue Webb, General Manager, UK & Ireland and Country President, Novartis UK, said the treatment “will make a real difference” to people living with MS.

The recommendation follows two previously failed appraisals. After the first in August 2011, Novartis submitted a Patient Access Scheme (PAS) to provide a discount to the NHS.

But, following another consultation, NICE said the MS pill still did not represent value for money in a separate draft guidance document last December.

However, during the second consultation period, Novartis revised its analysis for a subgroup of patients for the licensed population. Following this, NICE’s independent Appraisal Committee now believes the treatment offers value for money to the NHS, when provided under the terms of the PAS.

The subgroup of patients includes adults with highly active relapsing-remitting multiple sclerosis, whose relapses have increased or remained compared to the previous year, despite the use of beta interferons.

NICE now provisionally recommends the treatment for adults who have an unchanged or increased relapse rate or ongoing relapses compared to the past year, despite treatment.

Dr Eli Silber, a consultant neurologist at King’s College Hospital, said she was delighted NICE reversed its original decision. “We’ve waited a long time for an effective oral treatment to offer patients who are continuing to relapse on first line injections,” said Dr Silber. “Today’s decision increases treatment choice. Because it is a highly effective oral agent it may change the way MS is managed in the UK forever.

“With more active forms of MS, we have a limited window of opportunity to make a difference to patients’ lives – many are young people who are raising families and starting their careers. I want to get appropriate patients onto this therapy as quickly as possible.”

The EMA has started a review into the benefits and risks of Novartis’ Gilenya (fingolimod) following concerns into cardiovascular effects in patients after the first dose.

The review begun after reports of heart problems in patients taking the multiple-sclerosis medication, as well as the unexpected death of one individual in the US less than 24 hours after taking the medication.

A further six unexplained deaths after treatment with Gilenya began have also been reported. Three of these were due to heart attack and one after the disruption of the heart rhythm. The EMA says it is not yet clear if these were caused by the medication or not.

The CHMP expects to complete the review by March 2012.

Gilenya has been authorised for use in the European Union since March 2011 for the treatment of patients with relapsing-remitting multiple sclerosis whose disease has failed to respond to a beta-interferon or is severe and getting worse rapidly. It has been used worldwide by more than 30,000 patients.

Doctors have now been advised to closely monitor patients after the first dose of the treatment has been administered. The medication’s product information does include recommendations for healthcare professionals to observe for signs and symptoms related to its side-effects for at least six hours after the first dose has been taken. The EMA says it was also aware of the risk of patients developing a slow heart rate after the first dose had been taken when it was authorised.

Novartis is cooperating with the review and has committed to supplying the CHMP with the results of its own investigations into the cardiovascular effects of Gilenya.

NICE has not recommended the use of Novartis’ Gilenya (fingolimod) for the treatment of a particular type of multiple sclerosis in provisional draft guidance.

Questions were raised by NICE’s independent Appraisal Committee over uncertainties of the drug’s clinical effectiveness based on Novartis’ evidence.

Professor Carole Longson, Director of the Health Technology Evaluation Centre, says Novartis did not provide “sufficient evidence” to show the treatment is better than other recommended options.

The Institute says that clinical trials have shown that Gilenya can reduce the number of relapses in certain people with RRMS. But it is unclear how much the treatment may help the specific group of people for whom it is licensed.

Gilenya is approved for adults who have highly active relapsing-remitting multiple sclerosis (RRMS) and experience at least one relapse a year, despite being treated with beta interferon, and for those with rapidly evolving severe RRMS who experience two or more relapses regardless of their treatment.

Novartis submitted evidence which focused solely on a sub-group of patients with rapidly evolving severe RRMS. The data also compared Gilenya with a placebo, and with a specific type of beta interferon that is not widely prescribed in the NHS.

Because of this the independent Appraisal Committee were unable to determine how much Gilenya reduces the rate of relapses compared with other recommended treatments. The Committee says that Novartis should’ve submitted a comparison with other beta interferons, and with the recommended Tysabri (natalizumab).

“While it’s important that people with multiple sclerosis have treatment options, NICE has to ensure that the NHS provides treatments that bring benefits that are value for money,” Dr Longson said. “This is so that everyone who uses the NHS can receive the best care possible.

“Based on the available clinical evidence and economic analysis, our independent committee concluded that fingolimod would not be effective good use of NHS resources.”

The draft guidance is now open to comment with final guidance expected in December.