Almirall takes on big pharma in COPD

Almirall presented the lead respiratory candidate at its R&D day in Barcelona last week, with the aclidinium bromide compound hailed as the cornerstone of the firm's respiratory franchise.

Last year the Spanish firm signed a deal with US company Forest Laboratories to develop, market and distribute the long-acting muscarinic antagonist in the US, and hopes to be able to launch the product in the EU by 2010.

The aclidinium inhalable product is intended as a long-term, once daily maintenance treatment of bronchospasm associated with COPD.

According to Almirall, it offers advantages over existing products in terms of side effect profile, as well as the novel dry powder inhaler (DPI) administration route.

The drug is currently being evaluated in a total of 17 studies, with a further 10 trials underway, two of which are in Phase III.

Results thus far have been very promising.

Aclidinium was found to be a high affinity M3 receptor agonist, with significant and long-acting bronchodilatory effects in patients with COPD.

The compound itself hydrolyses rapidly in human plasma and therefore has a short half life of less than 15 minutes, a key factor in reducing the chances of systemic side effects.

Other anticholinergic COPD treatments, such as tiotropium or ipratropium, can last for hours or even days in the body, increasing the likelihood of these unwanted side effects.

While aclidinium may vanish from plasma very rapidly, therapeutic benefit in the lungs is also very quick, with onset of action within 15 minutes and lasting for 24 hours.

Combine these advantages with a revamped inhaler device that promises ease of use, efficient drug delivery and features to aid compliance, and Almirall believes it is on to a winner.

The company's inhaler device is based on an existing product that has been on the market for some time, but Almirall has improved on the design for its aclidinium treatment.

"We tried to make it simple," said Almirall's director of pharmaceutical development, Carsten Niederlaender.

"Make it hi-tech, but keep the hi-tech inside and don't bother the patient with it."

The result is a reservoir-based DPI that has been kitted out to tackle some of the key criticisms of existing inhaler products.

The inhaler has been designed to operate according to a single press-and-inhale concept, with feedback mechanisms to ensure patients can be confident that they have taken the correct dose.

To use the device, the patient removes the cap and presses down on the dosage release button until an audible 'click' is heard.

At this point the visual feedback mechanism also kicks in, with a panel in a small window on the device switching from red to green to alert the user that the inhaler is charged with the drug.

The patient then inhales through the device, with a sufficient breath triggering another audible click and the coloured panel to switch back to red, confirming that the patient has taken the medicine.

Almirall has also formulated the drug to contain a small amount of lactose as a carrier, which results in a sweet taste as it is delivered - another feature to ensure patients know that the drug has been successfully discharged.

The inhaler also incorporates a dose counter to alert patients when their medication is running low, and also has a built in 'lock-out' mechanism to prevent the device being mistakenly used once the drug canister is empty.

"It's not a completely novel device, but it's state of the art…ease of use was foremost," says Niederlaender.

With the incidence of COPD on the increase, rising 163 per cent between 1965 and 1998 (compared to heart disease, stroke and other cardiovascular ailments that have all seen a decline over this period), there is clearly a market for Amlirall's product.

Next year the firm plans to present additional data from ongoing studies, and is also developing aclidinium combination products containing formoterol or inhaled corticosteroid.

The company's confidence in the product is practically palpable, with Almirall's Gonzalo de Miguel using last week's R&D day as an opportunity to voice the firm's enthusiasm for its lead respiratory candidate: "We think it's going to be a star," he said, " the jewel in our crown."