Immtech Drops on Halted Clinical Trials

Immtech Pharma (IMM) put on hold its Phase III clinical program for pafuramidine, a treatment for pneumocystis pneumonia [PCP] (an HIV/AIDS related illness) and African sleeping sickness. Immtech is conducting worldwide trials of pafuramidine and recently added a China arm. The drug was given Fast Track status by the SFDA earlier this year.

In South African labs, observers noted that trial volunteers had abnormally high liver toxicity readings.

In the U.S., pafuramidine is considered an orphan drug and does not have a large patient population in which to conduct a clinical trial. As a result, Immtech was performing auxiliary safety studies of the drug in South Africa to satisfy the FDA that the drug had been tested in a sufficiently large cross-section of people. The China arm of the Phase III trial, added in late November, was a strategic move that simultaneously added patients to the U.S. trial and advanced the drug toward SFDA approval.

In the South African study, volunteers were administered 100 mg of pafuramidine twice a day for 14 days (a placebo arm was also part of the study). The active cohort has not suffered any deaths, nor have any hospitalizations occurred. Immtech raised the possibility that the trial would recommence once the patients had returned to baseline and experts in liver toxicity could review the data. Immtech will then present the data to the FDA and make recommendations.
The news cut the price of Immtech’s stock almost in half. It dropped $2.79 to $3.06, a 48% decline in extremely active trading.

Disclosure: none.

Comments

[pbd@entheol...:]

ABSTRACT: The pharmaceutical development of pafuramidine (DB289) as an orally administered antimicrobial diamidine prodrug was discontinued by Immtech Pharmaceuticals, Inc. (Amex:IMM) on February 22, 2008 because of unexplained idiosyncratic drug induced organ toxicity (IDIOT). The unexpected IDIOT seen in a recent Phase I safety study can be explained in terms of the mechanism of action (MOA) for pafuramidine and in view of differential drug absorption, distribution, metabolism and excretion (ADME) as between healthy subjects and infected patients. Human healthy subjects (volunteers) are NOT appropriate subjects for testing the safety of an oral pafuramidine dosing protocol that ultimately will be used to treat patients that have serious infections (such as African sleeping sickness, PCP or malaria). The ADME for healthy volunteers should be different than for infected patients. Healthy subjects should absorb more pafuramidine relative to infected patients and therefore be at a higher risk of drug induced organ toxicity. The maximum tolerated dose (MTD) of oral pafuramidine that will be safe and effective for treating seriously infected patients probably will NOT be safe (as safe) when tested in health volunteers.
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2008 Apr 22 07:36 PM