Exubera has opened door for pulmonary delivery growth

Other already in development include interleukin-1 receptor for asthma, heparin for blood clotting, interferons for multiple sclerosis or hepatitis, and calcitonin for osteoporosis. "

Nearly every biotherapeutic product that treats chronic or long-term illness would benefit from non-invasive delivery by providing a competitive advantage to current therapeutics," comments Mary Anne Crandall, author of a new report from Kalorama Information, Drug Delivery Markets 3: Pulmonary Delivery Systems .

With technological advances such as dry powder inhalers and growing demand for easier ways of administering drugs that are often available only through injection, the pulmonary drug delivery market worldwide is expected to reach $34.5 billion by 2010, showing compound annual growth of 7.8% since 2006.

The market expanded at an even more energetic rate between 2002 and 2006, with compound annual growth of 9.9% to $25.5 billion, according to Kalorama's estimates.

Most of the momentum in pulmonary drug delivery will continue to come from inhaled therapies, Kalorama believes.

"Novel dry-powder formulation, processing and filling, combined with aerosol device technology, will provide many patients who previously received injections with the ability to independently and painlessly inhale medicine into the deep lung, where it will be absorbed into the bloodstream naturally and efficiently," the report says.

In terms of the drugs delivered by pulmonary means, 77.4% of the overall market in 2006 - $18.5 billion out of total revenues of $23.9 billion - came from products incorporating pulmonary rather than intranasal delivery systems, compared with 77.0% in 2002.

By 2010, drugs delivered through inhalation are forecast to generate revenues of $25.6 billion, accounting for 78.3% of a total market projected at $32.7 billion.

Revenues from drug delivery technologies alone climbed from $1.4 billion in 2002 to $1.6 billion in 2006 and will reach $1.8 billion by 2008, Kalorama believes.

With asthma still the mainstay of the pulmonary delivery market, inhaled therapies continue to attract the most interest, Crandall points out.

Nonetheless, intranasal drug delivery offers a number of benefits such as convenience (for example, as an alternative to injections for long-term calcitonin users), a means to bypass first-pass metabolism in the gastrointestinal tract, and a rapid mode of action.

At the moment, the report notes, drugs that that need to act quickly on the heart, such as nitroglycerin, are given sublingually so that they are directly absorbed into the venous system and reach the heart quicker than via the arterial system.

"Nasal delivery of compounds, especially vaccines, has been investigated for some time, with the hopes of creating a novel system that can be easily distributed to end users, is simple to administer, and is accurate and efficacious," it adds.

"Targeting the nasal mucosa may be a means to enhance the immune response of certain vaccines and because of the IgA antibody system, a means to provide more effective immunisation for a variety of sexually transmitted diseases."

Exubera expectations "too high" In the core inhalation segment, Kalorama does not make any forecasts for Exubera but has factored the product's current difficulties into its overview of the sector.

" Exubera, as the first inhaled insulin product, was an exciting development in this category, however expectations were too high and the product's sales disappointing," Crandall comments.

"There appears to be a problem with too much of the insulin being retained in the lungs …The concern in transporting a drug to the large surface area of the lungs is to make a particle small enough to penetrate deep into the lungs, yet large enough to not come back out with a breath.

As new products come out, this balance should be achieved."

Some of the immediate, near-term forecasting for inhaled insulin "has been off due to projected sales of Exubera that aren't going to happen in its current form," she adds.

"But Kalorama does not believe this is the end of the category of inhaled insulin.

Far from it; in fact, Exubera has introduced the idea and offers a road map of what to fix before the next launch."

MannKind has a similar product in development - Technosphere insulin for Type 1 and 2 diabetes - that will directly compete with Pfizer's product.

Crandall notes: "The product is more compact and is an inhaled short-acting formulation."

Despite the long-established use of inhalation technologies in the respiratory category, there is still room for improvement in a number of areas, including deposition efficiency, targeting and sustained release, the report says.

"Currently, several novel particle methods such as spray freeze-drying into liquids, supercritical fluid technology, and crystal engineering have been developed to overcome the limitations of the conventional methods of spray drying and jet milling," it observes.

"You've got to get enough medicine to the patient, but not so much that there are deposits in the lung and not so little that the patient exhales it: a challenge, but not insurmountable," Crandall remarks.

"The potential is there, because the huge surface area [of the lungs] provides potential for rapid and non-invasive action.

But getting medication to the lungs and avoiding build-up in either the lungs is the challenge … they are close: expect to see the next five years of products address these challenges significantly."

The less than stellar performance of Exubera has not been helped by concerns over potential side-effects and costs, with both the UK and Germany in Europe judging the new product's cost-effectiveness insufficient to warrant full reimbursement.

However, Crandall does not see this setting the tone for the emerging inhaled insulin market.

Cost is "a guarantor of the survival of this type of delivery mechanism," she insists.

"Inhaled insulin is a far cheaper delivery mechanism, and that will drive the inhalation market.

Payers want a cheaper mechanism, and the company that gets it first will be rewarded.

Pfizer may not have been able to get its blockbuster but no one should dismiss the category on that example."