Washington Editor

Danish biotech Zealand Pharma AS and its partner Sanofi-Aventis Group SA reported that their Type II diabetes drug lixisenatide (AVE0010), a once-daily injectable glucagon-like peptide-1 agonist, significantly reduced hemoglobin A1c vs. placebo and improved glycemic control in patients with Type II diabetes, meeting its primary endpoint in a 12-week Phase III trial.

But JP Morgan analyst Cory Kasimov said he doubted lixisenatide would be a threat to Bydureon, the once-weekly GLP-1 being developed jointly by Amylin Pharmaceuticals Inc., Alkermes Inc. and Eli Lilly and Co. That drug, however, received a complete response letter last month from the FDA. (See BioWorld Today, March 16, 2010.)

Nonetheless, San Diego-based Amylin's and Waltham, Mass.-based Alkermes' shares slid slightly in Thursday's trading, while Lilly's stock (NYSE:LLY) rose 13 cents to close at $36.72. Shares of Amylin (NASDAQ:AMLN) were down 34 cents, to close at $22.37, while Alkermes shares (NASDAQ:ALKS) closed at $13.57, a loss of 18 cents.

Bagsvaerd, Denmark-based Novo Nordisk AS (NYSE:NVO), whose once-daily GLP-1 compound Victoza (liraglutide) gained FDA approval in January for Type II diabetes, also saw its stock take a minor hit Thursday, falling 35 cents, to close at $80.64. (See BioWorld Today, Jan. 27, 2010.)

Zealand CEO David Solomon, whose privately held company licensed the exclusive worldwide rights of lixisenatide to Paris-based Sanofi in 2003, said the top-line results, which he said showed that the drug was not only effective but well tolerated with lower adverse effects than its potential competitors, were "terrific news."

While Solomon said he could not disclose whether his company would receive any major payments tied to lixisenatide's positive Phase III data, he noted that the deal with Sanofi, whose terms have not been fully disclosed, included "significant" milestones, double-digit royalties and has helped put Copenhagen, Denmark-based Zealand in a position to not have to raise funds "until we are revenue-positive.

"We have not had to raise further money since January 2006, and will not have to," he told BioWorld Today. "That really speaks to the condition of our partnerships," he said, noting that his company has other deals in the works, including one with Helsinn Healthcare SA and another with Wyeth, now part of New York-based Pfizer Inc.

Solomon said his company has six other candidates in the pipeline "all of high value. This all speaks to Zealand being a company with a durable pipeline, with a very bright future," he insisted. While the company has four global partnerships, "and Sanofi is but one, it is clearly the most advanced partnership in largest indication of any of our drugs," Solomon said, adding that the Paris drugmaker has had one of the most "determined and successful" diabetes franchises globally.

Sanofi's Lantus (insulin glargine [rDNA] injection) - the world's largest selling long-acting insulin product - had worldwide sales of about $4.3 billion in 2009, noted JP Morgan's Kasimov.

"They will be able to sell and market this drug once it is approved very well," Solomon said.

Top-line results of the GetGoal Phase III trial - the first of nine Phase III trials to be reported - showed that lixisenatide significantly reduced HbA1c vs. placebo with more patients achieving HbA1c below 7 percent and improved glycemic control in adult patients with Type II diabetes, Sanofi said.

The study randomized 361 patients with Type II diabetes not currently receiving glucose-lowering therapy and with HbA1c between 7 percent and 10 percent to one of four once-daily treatment regimens: lixisenatide two-step titration at 10 ug once daily for one week, 15 ug once daily for one week, then 20 ug once daily; lixisenatide one-step titration 10 ug once daily for two weeks, then 20 ug once daily; or placebo one step or two-step titration.

Baseline characteristics were similar among groups in terms of mean age, diabetes duration and HbA1c, Sanofi reported. HbA1c was significantly reduced in both lixisenatide titration groups vs. placebo, and significantly more patients in the lixisenatide groups achieved HbA1c below 7 percent, 46.5 percent to 52.2 percent vs. 26.8 percent.

Sanofi said lixisenatide also significantly improved fasting plasma glucose and two-hour post-prandial glucose, with a pronounced decrease in two-hour post-prandial glucose excursion. The most common adverse event in the study was nausea occurring in 20 percent to 24 percent of lixisenatide-treated patients, vs. 4 percent in the placebo group, Sanofi said.

"This is among the lowest nausea rates seen in these drugs," Solomon said, noting that the occurrence of nausea in Type II diabetes patients taking Novo Nordisk's Victoza was about 28 percent. "So we think this is good," he said.

The incidence of symptomatic hypoglycemia in lixisenatide-treated patients was low at 1.7 percent, with similar results in the placebo groups, Sanofi said.

The company's Phase III lixisenatide GetGoal program, which was initiated in May 2008, was designed to include multicenter, randomized, placebo or active-controlled studies, Sanofi said. The program has enrolled more than 4,500 patients, the firm added.

Solomon noted that Sanofi plans later this year to launch a combination clinical program of lixisenatide and Lantus, which loses patent protection in 2014.

"The lixisenatide-Lantus combination is the likely replacement for Lantus," Solomon said. "That they are embarking on the Phase III studies is a further commitment to not only their diabetes franchise, but also to advancing another differentiation modality of lixisenatide by pairing it with a very successful long-acting insulin."

He said he expected a Lantus-lixisenatide combination therapy to be a "very viable blockbuster drug for Sanofi."

In addition to being a "very strong lifecycle management" for both drugs, the combination product also would greatly benefit patients and prescribers, Solomon insisted.