TMCnet News
MannKind Shares Take a Hit; Was it Data or Exubera Deal?(BioWorld Today Via Acquire Media NewsEdge) It was unclear whether it was MannKind Corp.'s not-yet-FDA-approved agreement to allow Exubera patients to use the firm's experimental inhaled insulin product Technosphere or the positive, yet uninspiring, Phase III results of the drug that had investors nervous Tuesday. Whatever the case, shares of the Valencia, Calif.-based firm (NASDAQ:MNKD) plummeted 13.6 percent Tuesday, or 46 cents, to close at $2.92. MannKind's preliminary top-line Phase III results showed that Technosphere inhaled insulin was comparable with Novo Nordisk AS' Novolog, a rapid-acting insulin analog, in regulating A1c levels in patients with Type I diabetes. Nonetheless, said analyst Thomas Russo, of R.W. Baird & Co., the "statistical close call on A1c control and less than eye-popping hypoglycemia benefit could be factoring into the market's reaction." The primary objective of the 565-patient Phase III 52-week trial was to compare the efficacy, as expressed by the change in A1c levels, of treatment with Technosphere vs. Novolog in patients with Type I diabetes. While Technosphere was deemed noninferior to Novolog on the primary endpoint of A1c control, it was directionally less effective, with the point estimate for A1c change -0.24 percent vs. the comparator, and a 95 percent confidence interval that did not include zero and touched the predetermined threshold of 0.40 percent, Russo noted. While fewer patients experienced adverse hypoglycemic events, that "may be viewed as less than inspiring," Russo said in a research note. There were no statistically significant differences in the percentage of patients whose A1c level decreased below 8 percent, 7 percent and 6.5 percent. Over the study's 52-week period, fasting blood glucose (FBG) levels decreased significantly in the Technosphere group compared with the levels observed in patients using insulin aspart. Among patients using Technosphere, mean FBG decreased by 48.8 mg/dL from 188.6 mg/dL at screening to 139.8 mg/dL at the end of the treatment period compared with a drop of only 20.2 mg/dL from 180.3 mg/dL to 160.1 mg/dL over the same period in the comparator group. Russo surmised that because those FBG results were "unexpected" and "difficult to explain," they would be the subject of further analysis. Patients in the Technosphere group also lost an average of 4.3 pounds over the treatment period compared with the average gain of 3 pounds in the comparator group, which was deemed statistically significant. With MannKind being the only inhaled insulin developer left, success of Technosphere is likely to depend on clinically meaningful differentiation beyond its pulmonary route of administration, Russo said. The "remarkable failure" of Exubera, which had been jointly developed by New York-based Pfizer Inc. and San Carlos, Calif.-based Nektar Therapeutics Inc., but exited the market in October 2007 after dismal sales, "made it obvious that the first key to success in the pulmonary insulin market is to not be Exubera," Russo declared, noting that drug's inconvenient bulky device and complexities in dosage and in training, along with concerns about lung safety. Technosphere could be the insulin product that offers benefits that differentiate it clinically from injectable forms of the drug and is viewed as safe, Russo said. But, he said, "we want to see more data and view pulmonary safety as the key." Peter Richardson, chief scientific officer for MannKind, said the firm's market research showed that Technosphere could fill the need for patients who want an alternative to injectable insulin, especially now that Exubera is no longer available and other attempts to develop an inhaled insulin product have been abandoned by Novo Nordisk AS and Eli Lilly and Co. Richardson said Pfizer approached his firm with a request to consider providing Technosphere to certain Exubera patients. However, MannKind and Pfizer have yet to work out the details with the FDA and drug regulators in Europe for a possible compassionate use or a special exception program, Richardson acknowledged. "We are jointly working on the approach for the agencies to handle this to develop the protocol and safety monitoring," he told BioWorld Today. "Both companies will be working together to ensure safe transfer of patients on Exubera" to Technosphere inhaled insulin, Richardson added. He said the firms are in "active discussions" with the FDA. While many of the Exubera patients have transitioned to other diabetes drugs, there remains a small number of patients with a need for inhaled insulin, specifically those with severe phobia to needles and those who are resistant to subcutaneous insulin, Richardson explained. He said the firms are expecting a "relatively small group" of patients to take part in the proposed program, "because it is a compassionate use protocol targeted to those patients with a clear unmet medical need who require inhaled insulin." The FDA for the past three decades has permitted expanded access to certain investigational drugs outside of controlled clinical trials. However, most of those circumstances generally have involved experimental drug use in patients with serious and life-threatening illnesses. The FDA in 2006 proposed regulatory changes to make experimental drugs more widely and easily available to seriously ill patients with no other treatment options and to clarify the circumstances and the costs for which a manufacturer can charge for an experimental drug. The FDA said the existing regulations do not adequately describe the full range of programs available, explicitly recognizing only emergency use for individual patients and widespread treatment use access for large groups of patients. Under a proposed rule, which has not yet been finalized, expanded access for experimental drugs would be available to individual patients, small patient groups and larger populations under a treatment plan when there is no satisfactory alternative therapy to diagnose, monitor or treat the disease or condition, according to the FDA. By clarifying and streamlining the processes, the agency said it hopes to encourage companies to make experimental drugs available and reduce barriers for health care practitioners in obtaining them. n ? ? Copyright ? 2008 Thomson BioWorld, All Rights Reserved. |