Medical Device Daily Executive Editor

MannKind (Valencia, California) — one of the companies indirectly impacted by this week's report, issued by Pfizer (New York), concerning cases of lung cancer associated with the use of the inhaled insulin product Exubera — released a statement distancing itself from Exubera and offering reassurance concerning the safety of its inhaled insulin product under development.

At the same time, it acknowledged being hurt by Pfizer's announcement and said it has put its search for a partner for its Technosphere inhaled insulin on hold.

Following Pfizer's report of cases of lung cancer found in those using Exubera (6 of 4,740 patients, vs. one in a control group, a variety of questions were raised by industry observers concerning the potential for winning regulatory approval of any inhaled insulin products currently in company pipelines.

The news sent Mannkind's shares down nearly 60%, from $3.50 to $2.35, and at least one analyst questioned the ability of the company to attract development or marketing partner for Technosphere. And Leewrink Swann downgraded the company to market perform from outperform.

The company's stock rebounded a bit to $2.53 at close yesterday after it issued its statement, and some analysts issued notes saying that the safety and tolerability of Technosphere is superior to Exubera.

Merrill Lynch agreed with that assessment of Technosphere but said that the product is Mannkind's "sole value driver" and it downgraded the company's stock to sell from neutral.

In its statement Mannkind referred to "the current market sentiment" concerning an inhaled insulin product and said it has decided to "suspend discussions" in pursuit of a partner for Technosphere.

Mannkind underlined Pfizer's contentions that there were no indicators that the cases of lung cancer were caused by Exubera and that those found with lung cancer had been cigarette smokers. But it said that Exubera had not been studied for carcinogenic risk.

In contrast, Mannkind said that Technosphere "has been examined in an extensive pre-clinical program, including a two-year carcinogenicity study in rats."

It said that that in those studies "Technosphere particles alone were well tolerated after daily inhalations for 104 consecutive weeks. There were no indications that our product or the carrier material alone had carcinogenic potential or caused cellular proliferation in the lungs.

"We also recently completed a six-month carcinogenicity study in transgenic mice that are prone to cancer. We found no macroscopic indications of carcinogenicity in animals treated with Technosphere Insulin or Technosphere particles for 26 consecutive weeks."

It said that the histology data from these studies is currently being reviewed and the analysis of them completed "later this quarter."

The company emphasized its belief that Technosphere is safe but that until safety and efficacy data is "confirmed" as a result of the Phase III studies, "we will be unable to achieve an appropriate valuation for Technosphere."

It said that the Phase III program is intended to provide safety/efficacy information concerning the product "in a broad group of patients with diabetes."

There had been no indication of a higher rate of lung cancer among those using Technosphere, compared to the general population, Mannkind said.

It added that it met with its monitoring board following Pfizer's report and concluded that the trials of Technosphere should continue.

It added also that there has been no evidence of pulmonary problems with the use of Technosphere as seen with the use of Exubera and that it is working with its monitoring board "to understand the implications of the Exubera data."

Alfred Mann, Mannkind founder, acknowledged the "negativity" currently surrounding the possibility of an inhaled insulin product but in interviews emphasized the lack of any "safety issue" surrounding his company's product.