Associate

Flamel Technologies SA again has partnered its recombinant human insulin product, Basulin; this time, signing a deal with Bristol-Myers Squibb Co. valued at up to $165 million.

The deal gives New York-based Bristol-Myers worldwide rights and hands it responsibility for leading and covering the costs of future development and manufacturing. It provides Flamel with a $20 million up-front payment, and the company could receive another $145 million in milestone payments.

Flamel's stock (NASDAQ:FLML) jumped $5.65 Wednesday, or 26.5 percent, to close at $26.95.

However, Flamel, of Lyon, France, once had the product partnered with Novo Nordisk A/S in a deal that ended in early 2002.

"We terminated [that deal] because Novo was not developing the product at the right speed that we were expecting," said Gérard Soula, president, CEO and director of research at Flamel.

The deal with Novo, of Bagsvaerd, Denmark, began late in 1999 and was broken in January 2002. The original terms included a $5 million up-front payment and had a total value of $42 million. At the time of termination, the company said it had received another $10 million from Novo since 1999. (See BioWorld Today, Jan. 14, 2002.)

Flamel has significantly bettered those Novo terms with its Bristol-Myers deal. If and when marketed, Flamel would receive double-digit royalty payments. Although Bristol-Myers now controls development, Flamel will provide support for certain activities.

Basulin is a controlled-release insulin product designed to be given once daily. Novo and Flamel had been working with an older version of the drug; the changes that have occurred since then are what enabled Flamel to strike the more financially rewarding BMS deal.

While it is the same drug, Flamel has optimized Basulin, and, perhaps more importantly when regarding the new deal, "turned to the clinic" to prove the product.

Soula told BioWorld Today that Aventis SA, of Strasbourg, France, and its diabetes product Lantus are "showing such good results that they are taking the market for long-acting insulin," something of a surprise since the diabetes leaders traditionally have been Eli Lilly and Co., of Indianapolis, and Novo Nordisk. If Flamel wanted to make a name for Basulin, it decided the best route would be to take on Lantus.

"Our goal was not to compare with Novo Nordisk but to compare with the best of the market today," Soula said.

Flamel ran a small Phase I trial comparing Lantus and Basulin. Results released in March showed Basulin demonstrated at least the same efficacy and had a similar pharmacokinetic profile as Lantus. That trial allowed Flamel to shop Basulin with a better package.

"We had more done than when we had signed the deal with Novo," Soula said. "We had improved the product and proved its efficacy against the best product on the market."

The product uses Flamel's Medusa technology to deliver insulin over an extended period. The key issue in delivering proteins, Soula said, is maintaining their 3-dimensional integrity. The Medusa technology involves a Flamel-designed nanoparticle that has the protein sitting on its surface, rather than encapsulated inside. When injected subcutaneously, the protein is slowly released from the surface of the nanoparticle under the skin and then absorbed into the bloodstream. Encapsulation, Soula said, requires a solvent, which denatures the protein.

Flamel has said it intended to begin Phase II trials in September, and that should progress as planned. Although the product is intended for both Type I and Type II diabetes, the indication for the upcoming trial will be decided by BMS.

Flamel has its Micropump technologies, designed to extend or delay the delivery of drugs, in several programs. It also has several preclinical programs under way for its Medusa technology. However, it has high expectations for Basulin.

"The reality is, today there is not a perfect treatment for diabetic people," Soula said. "We see a huge potential for improvement."