A Medical Device Daily

Delivering to Novo Nordisk (Bagsvaerd, Denmark) a key piece of the puzzle for its inhaled insulin system, Aradigm (Hayward, California) last week reported giving patent rights covering glucose control in exchange for $27.5 million in payments.

The agreement gives Novo everything it needs to bring the AERx Diabetes Management System (iDMS) to market, which could occur upon conclusion of a Phase III program in three years. The company restarted trials in May.

Christopher Keenan, Aradigm's director of investor relations, called the restructured partnership the “evolution of an agreement“ begun in 1998, when the companies first joined to develop iDMS. But in May 2004, concerns over a secondary endpoint during a Phase III interim analysis led the firms to halt the program, sending Aradigm's shares downward by nearly 30%, and eventually resulting in Novo's $55 million buyout of the development and manufacturing rights to iDMS in September of that year.

“The manufacturing piece was [announced in 2004 and] executed in January 2006, and with this transfer of intellectual property they are really able to collectively have a solid footing in this area to launch it,“ Keenan told Medical Device Daily's sister publication, BioWorld Today.

Under the original 1998 agreement, Novo would pay license fees for rights to the iDMS patents. Under the restructured agreement, Aradigm will receive $12 million upon transferring the ownership of certain patents related to inhaled insulin, as well as $8 million for reducing its average royalty rate on the AERx product from 6% to 5%, and $7.5 million in a 5%, eight-year note payable in three payments beginning in six years.

Aradigm retains exclusive control of the patents outside the field of glucose control. Every program the company has in development touches upon the patents, Keenan said, including its Phase II program in asthma and another in bioterror-related anthrax.

The trouble with the previous iDMS Phase III program had to do with a delay in post-meal plasma glucose suppression in Type 1 diabetics. While the drug met primary safety endpoints in the interim analysis, and even though overall blood glucose levels were being controlled, glucose levels following meals were higher in those receiving insulin through the AERx system, as opposed to those given subcutaneous insulin.

Since then, Novo Nordisk has studied the dosing regimen to see if anything could be tweaked. But in the meantime, Exubera, with which Nektar Therapeutics (San Carlos, California) is involved, became the first inhaled insulin product approved by the FDA. That approval followed communication by an FDA advisory panel that the agency was not as concerned about post-meal glucose levels as it was about overall glucose levels, Keenan said.

“That was a relief to us, but if we had known that, I don't know if we would have stopped the [iDMS] trial“ in 2004, he said.

Exubera gained FDA approval in January. Nektar developed the drug in collaboration with Pfizer (New York). Analysts have said sales could exceed $2 billion in five years, and inhaled insulin could eventually cannibalize injectable insulin.

Aradigm said it is the only company working in the liquid delivery of insulin, meaning its product uses no additives or excipients and Aradigm said it is more cost-effective than other prospective products. Its candidate also takes the “guesswork“ out of delivering the drug, Keenan said, because it is dosed “in single unit dose increments. There is no math. Patients know how much they need.“

Others working in the field include MannKind (Valencia, California), which in March started two Phase III studies of its inhaled insulin product, Technosphere Insulin. A month later, Alkermes (Cambridge, Massachusetts) started a third Phase III trial in Type II diabetes comparing its AIR Inhaled Insulin System with injectable pre-meal insulin.

Diabetes affects an estimated 194 million adults worldwide, or 20.8 million in the U.S. Injectable insulin has been used for more than 80 years to control glucose levels, and represents a $3-billion-plus market.

Novo Nordisk and Aradigm expect to gain a share of that pie with iDMS.

“We do hope Exubera does well, and we do hope it paves the way for patient acceptance,“ Keenan said. “We'd be very happy to be the second to market.“

Aradigm also is working on a special formulation of ciprofloxacin for cystic fibrosis and an inhaled pulmonary arterial hypertension drug in partnership with United Therapeutics (Silver Spring, Maryland).

New distribution, production facilities for Orthofix

Orthofix International (Huntersville, North Carolina) reported the opening of its new International Distribution Center, located in Verona, Italy.

The company said the new facility is designed to increase its operational efficiency in Europe by centralizing production, logistics and customer service functions previously located in the UK and the Seychelles. It said these changes are expected to result in pre-tax savings of more than $1 million annually starting in 2007. Orthofix said it expects additional savings to result from reductions in inventory levels and related carrying costs.

The distribution center also is expected to benefit the company's customers by lowering their shipping costs and reducing shipping times by an average of at least one day. “This is another step in our comprehensive international restructuring plan intended to improve operations,“ said Orthofix CEO Alan Milinazzo.

The restructuring plan previously announced by the company includes the creation of three business zones around the world organized to address regional customer requirements and ensure that they are incorporated into the design and distribution of Orthofix's products and therapies.

The new facility, which includes more than 18,000 square feet of space, already has begun distributions for the company's UK-based subsidiary, Orthofix Ltd., after completion of the transfer of operations from an external contractor. The center also is distributing European orders for BREG, Orthofix's California-based subsidiary that specializes in functional bracing, pain management and cold therapy products.

The new facility also is expected to begin distributing AV-Impulse products for the firm's Novamedix subsidiary later this month.

When fully operational, the facility is expected to distribute at least $65 million in Orthofix products annually to customers outside the U.S.

Orthofix also said it has relocated its production operations in Italy to a new 8,600-square-foot space adjacent to the distribution center. This new space, which serves as the production site for about 20% of the company's products manufactured in Europe, is almost double the size of the company's previous facility.

Orthofix International offers a broad line of minimally invasive surgical, as well as non-surgical, products for the spine, reconstruction and trauma market sectors.

Primagen says DFS tech is validated

Primagen Holding (Amsterdam, the Netherlands), an emerging company in molecular diagnostics for infectious diseases and cancer, said that its special dry filter paper (DFS) technology has been internally validated for use with the Roche Cobas Amplicor HIV-1 test v 1.5.

With the Primagen DFS system, body fluid samples (e.g. blood, plasma, urine, mother's milk, etc.) are sent as dried spots on Primagen filter paper to central testing laboratories that provide HIV-1 viral load testing services. The DFS samples are stable for months at ambient temperature, do not require any special handling (e.g. time limitations, refrigeration or dry ice) and, most importantly, are not infectious.

The company said DFS would give HIV/AIDS care providers a simple, cost-effective sample collection system for patients requiring monitoring of their HIV-1 viral load using tests including the Roche Cobas Amplicor test.

Full results of the study were presented at the 14th International Symposium on HIV and Emerging Infectious Diseases in Toulon, France, in the latter part of June.

“With Primagen's DFS technology, care providers can monitor more HIV-1 patients because samples are simpler to collect and cost less to transport when in a non-infective state,“ said Bob van Gemen, CEO of Primagen. “These benefits are particularly important in resource-poor settings, where, if healthcare providers can lower the cost of sample collection and shipment, they can free up funds for patient care.“

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