Skye formulation accepted for GSK drug

The new formulation allows the extended release of the drug over a period of 24 hours, creating a once-daily tablet for the treatment of Parkinson's disease.

The new product, provisionally named Requip XL 24-Hour, will provide an alternative treatment option to GSK's immediate release formulation of the drug, which is administered three times a day.

The once-daily formulation uses SkyePharma's proprietary GeoMatrix technology, the core of the company's oral delivery platform.

The GeoMatrix systems are applied to achieve customised levels of controlled release of specific drugs, and can achieve simultaneous release of two different drugs and different rates from a single tablet.

The controlled release is achieved by constructing a tablet made of two basic components, hydroxypropyl methycellulose (HPMC) and one or more barrier layers.

The HPMC core contains the drug's active ingredient, and the combination of barrier layers control the surface area diffusion of the drug (or drugs) out of the core.

The combination of layers, each with different rates of swelling, gelling and erosion, is responsible for the rate of drug release within the body.

When first swallowed, for example, the drug concentration is high but the surface area low.

As time progresses the core swells, and the surface area increases to make up for the decrease in drug concentration.

According to the company, one of the major benefits of the GeoMatrix technology is its ability to be easily incorporated into the production line.

The firm claims that GeoMatrix tablets can manufactured by readily available equipment that can be integrated into widely-used pharmaceutical processes, thus giving firms more control over their own production activities.

SkyePharma already manufactures three GeoMatrix products, Coruno (Molsidomine) for Therabel, diclofenac for Ratiopharma and Madopar (levdopa and benserazide) for Roche, another treatment for Parkinson's disease.

The company is also working on an extended release formulation of Sular (nisolpidine), a calcium chnnel blocker, in partnership with Sciele Pharma.

If approved for Parkinson's disease, future sales of the Requip XL 24-Hour product are set to generate 'low mid-single digit' royalties for the company.

While not on the scale of the company's hopes for its asthma treatment Flutiform (fluticasone and formoterol), which is seen as a potential billion-dollar product with royalty percentage in the mid-teens according to chief operating officer Ken Cunningham, the extended release Requip product is set to make a healthy contribution to SkyePharma's coffers.

"It's a bit like another Paxil," said Cunningham, referring to the paroxetine product the company has marketed with GSK, through which Skye gets a 4 per cent royalty.

Earlier this month GSK reported positive results of a trial studying the efficacy of the once-daily Requip tablet taken along with Parkinson's patients' existing levdopa therapy.

The combination of the two reduced a common symptom of Parkinson's known as 'off' time by more than two hours a day.

"'Off' time is a common phenomenon for Parkinson's patients," said Rajesh Pahwa of the Parkinson Disease and Movement Disorder Center at the University of Kansas who led the study.

"When symptoms like slowness of movement, tremor and rigidity return due to wearing off of the patient's medication, it can be problematic, causing difficulty with simple activities and movement in patients with Parkinson's disease."

Reducing this period of 'off' time allows patients to carry on their normal daily activities for a longer period of time, making it an attractive option for Parkinson's sufferers.

In addition to this, a once-daily regimen could significantly help improve compliance over a thrice-daily dosage.

Requip has been tagged as a high value growth product for GSK, with the immediate release version performing well in the US and total sales during 2006 growing 74 per cent to hit £268m (€393.7m).

These sales are expected to be boosted by two follow-on products, the once-daily tablet for Parkinson's and Requip CR for Restless legs Syndrome, which was accepted for approval by the FDA in December last year.

GSK highlights Requip as one of its 'rising stars' for 2007 sales (along with Avodart (Dutasteride) and Boniva/Bonviva (ibandronate)), though has cautioned that these gains are likely to be offset by declines in Zofran (ondansetron), Flonase (fluticasone) and Wellbutrin (bupropion) due to generic competition.

The 24-hour formulation is already in the regulatory process in Europe, with the first approvals and launches anticipated for later on this year, said Cunningham.

Although approval in the US is slightly behind the European application, Cunningham suggested that it could feasibly be achieved by the end of 2007.