Shares of Immtech Pharmaceuticals Inc. plunged for the second time in two months after the company said it was discontinuing development of lead drug pafuramidine due to safety concerns.
The New York-based firm's stock (AMEX:IMM), which lost slightly more than half its value, dropping to $2.88, in late December on news of liver abnormalities seen in a South African study of pafuramidine in a volunteer safety trial, fell 92 cents, or 46 percent, to close Monday at $1.08.
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 (trypanosomiasis) and Pneumocystic carinii pneumonia, 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, this 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."
In the wake of pafuramidine's discontinuation, Immtech intends to redirect its resources toward its preclinical pipeline. The company has "a library of compounds in the same class" as pafuramidine, meaning aromatic cationic compounds, Berry told BioWorld Today.
Those programs are targeting fungal infections, hepatitis C and drug-resistant bacterial infections. Berry said the firm has not yet provided a timeline for moving those into the clinic.
At this time, Immtech has not reported plans to restructure or to cut any of its 28 employees. But the company undoubtedly will have to bring in some additional capital to advance its pipeline. For the three month period ending Dec. 31, Immtech reported a net loss of $5.3 million, or 34 cents per share, and had cash and cash equivalents totaling $9.4 million.
By shelving pafuramidine, the company also will lose out on potential milestone payments from its collaborations with Par Pharmaceutical Cos. Inc. and BioAlliance Pharma SA. The June deal with Par subsidiary Strativa Pharmaceuticals, of Woodcliff, N.J., involved a $3 million up-front fee for rights to market pafuramidine in PCP in AIDS patients. Immtech also could have received as much as $29 million in milestone payments through approval, plus up to $115 million in sales-based milestones and royalties under the deal, but the discontinuation means Strativa owes no further payments. (See BioWorld Today, June 13, 2007.)
Nor does Immtech expect any additional payments from Paris-based BioAlliance, which it signed to a partnership only weeks before reporting the clinical hold. That agreement, for European commercialization rights to pafuramidine, called for BioAlliance to pay an initial $3 million. Had the program advanced, Immtech could have received another $13 million in milestones through European approval, plus sales-based milestones and double-digit royalties.
In a separate press release, BioAlliance said it will not be deterred by the disappointing pafuramidine news and plans to continue pursuing its strategy to acquire late-stage compounds for European oncology and HIV markets.
Immtech's news, however, is a blow to the small sleeping sickness patient population. The World Health Organization estimates about 11,000 new cases of African trypanosomiasis every year in the sub-Saharan region of Africa. The disease, transmitted by the tsetse fly, produces a number of symptoms, from anemia to neurological disorders, and is fatal without treatment, though existing treatment options are toxic and require long infusion processes.
Besides Immtech, only a few firms are pursuing drugs for trypanosomiasis, which is considered a neglected tropical disease, and most of those are in early stage development. One of those firms, Vancouver, British-Columbia-based Upstream Biosciences Inc., has garnered headlines lately with recent collaborations with universities in Moscow and Uganda focusing on parasitic diseases, but its programs for African sleeping sickness still are in preclinical testing.