BioWorld International Correspondent

PARIS - Following the decision by Immtech Pharmaceuticals Inc. to halt the development of pafuramidine maleate, BioAlliance Pharma has issued a statement reasserting its commitment to continue looking for compounds to in-license in the areas of oncology and HIV.

Immtech Pharmaceuticals, of New York, had been developing pafuramidine for the treatment of pneumocystis pneumonia (PCP) in HIV patients and human African trypanosomiasis, also known as African sleeping sickness. But it announced last December that the program had been placed on clinical hold following an unexpected adverse event related to liver abnormalities identified in volunteers participating in a trial in South Africa.

Since then, Immtech has received information about abnormal kidney function during the follow-up of the volunteers in the same trial. As a result, it informed BioAlliance on Feb. 22 that it was to "discontinue all Phase III programs concerning its novel chemical entity pafuramidine" and instead to "focus on its novel anti-infectives."

According to BioAlliance, "the cause of the liver and kidney toxicity has not yet been fully clarified but the decision to discontinue the pafuramidine development program was taken by Immtech and the independent data safety monitoring board following a risk-benefit analysis of the compound."

Dominique Costantini, president and CEO of Paris-based BioAlliance Pharma, responded to the Immtech decision by issuing the following statement: "Pafuramidine's Phase II results were promising and did not raise any particular safety concerns. We were thus hopeful that this compound would successfully complete its pivotal Phase III clinical trial in patients with PCP. BioAlliance Pharma will actively pursue its product acquisition strategy in order to add complementary compounds to its own portfolio. We are seeking products for treating chemotherapy complications or rare diseases in oncology or HIV, for example."

It was only in early December that BioAlliance Pharma signed an exclusive licensing agreement with Immtech Pharmaceuticals for the European sales rights to pafuramidine. It now has confirmed that its financial exposure is limited to the $3 million it paid up front.

In January, BioAlliance Pharma obtained marketing approval in the UK and Denmark for Loramyc, its topical formulation of miconazole for the treatment of oropharyngeal candidiasis in immunodepressed patients. It currently is preparing to launch the product in several European countries, having launched it in France last year.

The New York-based Immtech's stock (AMEX:IMM), which lost slightly more than half its value, dropping to $2.88, in late December on news of liver abnormalities in a volunteer safety trial, fell another 90 cents, or 45 percent, to close Monday at $1.10.

Those December reports prompted a clinical hold on pafuramidine, an aromatic cationic compound designed to bind to segments of DNA to block enzymes enabling microbial growth. At that time, the drug had progressed into Phase III studies in the orphan indications African sleeping sickness and PCP, the most common opportunistic infection in HIV patients.

Immtech had started to analyze the liver data from that safety study when more recent reports showed additional adverse events, that time affecting kidney function, in a cohort of volunteers in that same study. Though the adverse events were confined to that one study - no similar trends had been observed in the earlier Phase II trials - the company opted to stop pafuramidine development for reasons of patient safety, said Bill Berry, spokesman for Immtech.

All affected patients continued to be monitored and are receiving medical care.

Meanwhile, the firm is conducting analyses to determine why that subset of patients showed apparent drug-induced hypersensitivity and inflammation in kidney biopsies. As to whether the data can be linked to the drug's mechanism of action, dosing schedule or target, Berry said, "they just don't know yet."