By Mary Welch

In what could be a giant step for the pharmacogenomic world, Variagenics Inc. paid $12 million for Nova Molecular Inc. (NMI) and its technologies used to develop new drugs for neurological diseases, including Alzheimer's disease.

Montreal-based NMI pioneered the clinical application of apolipoprotein E (ApoE) to predict patient responses to drugs for Alzheimer's disease and other central nervous system (CNS) disorders. It is the first clinically validated pharmacogenomic marker used in clinical trials.

"The ApoE marker has really gotten the attention of the pharmaceutical industry," said Fred Ledley, president and CEO of Cambridge, Mass.-based Variagenics. "The marker shows which Alzheimer's drugs work for some patients based on their variant forms of the ApoE gene, specifically the ApoE4 variant."

Studies have shown that the normal ApoE protein is involved in CNS cell repair. In people with the ApoE4 variant, the repair process may be lessened. Those with a normal ApoE respond better to common Alzheimer's drug Cognex (tacrine) and other similar compounds, suggesting that ApoE may have an important role in determining the most appropriate therapy for many disorders of the central nervous system.

For a company aiming to test the efficacy of a potential treatment for Alzheimer's disease, knowing if the enrollee is ApoE4 variant could be used in determining whether the patients will respond to the drug.

Under the terms of the agreement, expected to be disclosed today, NMI gives Variagenics exclusive rights to its broad intellectual property portfolio covering the pharmacogenomic application of ApoE and other genetic markers for the treatment of CNS disorders. Eventually, NMI will be reorganized into a new parent corporation that will continue operations as an independent company in Montreal, and will expand its capabilities for pharmacogenomic association studies. Judes Poirier, an associate professor in the department of psychiatry at McGill University, will join Variagenics as principal scientific advisor.

"There are a lot of reasons to keep NMI a Canadian-owned company, not the least of which is that we want to keep our associations with McGill University, as well as the fact that we believe that the pharmacogenomics industry will really be building in Canada," Ledley said.

Quintiles Alliance Also Fits The Strategy

Pharmacogenomics tries "to understand how normal genetic variation in patient populations affects drug action and by applying this information, can help in the development and clinical use of pharmaceutical products," Ledley said. "This information, for instance, can help a drug that might not get approved have successful trials. By considering the effects of genetic variations in clinical trials, these trials will increase the efficiency and success rate of new drug [development] and expand the market potential for many drugs. It will also help health care providers prescribe drug regimens, customized for each individual patient, that are most likely to be safe and effective."

Strengthening its ability to deliver these markets to the pharmaceutical industry is Variagenics' recent alliance with Quintiles Transnational Corp., of Research Triangle Park, N.C. Quintiles will market Variagenics' genetic variance discovery and analysis capabilities to its broad customer base of pharmaceutical and biotechnology companies engaged in clinical trials.

Although the ApoE gene is Variagenics' largest marker deal to date, the privately owned company has also licensed the thiopurine methyltransferase (known as TPMT) gene for diagnostic and therapeutic purposes from the May Foundation for Medical Education and Research, in Rochester, Minn. Diagnostic tests for mutations in the TPMT gene can be used to identify patients in whom certain immunosuppressive drugs, such as azathioprine or 6-mercaptopurine, can be used safely.

Patients with mutant forms of the TPMT gene may suffer a life-threatening toxic reaction if treated with these immunosuppressive drugs, which are indicated for cancer, transplant rejection and rheumatoid arthritis. Diagnostic tests for TPMT mutations can be used to identify patients in whom these drugs can be safety given.