Isis-301012 was shown to reduce levels of low density lipoprotein (LDL) - also called 'bad' cholesterol as it is linked to increased heart disease and stroke. The results from three separate Phase II clinical trials were presented this week at the American College of Cardiology Annual Scientific Session (ACC) in New Orleans. The positive results will provide a welcome boost for antisense drug developers in general. The once hyped sector suffered a series of knock backs late last year with drugs being refused approval or scrapped totally. "The data are compelling. These are really elegant studies, carefully executed and thoughtfully analyzed," said Dr Thomas Michel, a Professor of Medicine at Harvard Medical School. "The conclusions are clear, and I am entirely convinced of the tolerability, activity and unparalleled therapeutic potential of Isis-301012." The drug is a second-generation antisense molecule that selectively binds to apoB-100, a protein critical to the synthesis and transport of LDL. In the trial, all of the 150 patients treated with Isis-301012 alone, achieved target levels of apoB and related harmful lipids at a higher dose and 75 per cent at a lower dose. When combined with statins, this second figure increased to 88 per cent. Isis also said the drug was well tolerated, with "no liver chemistry findings that would suggest risk of drug-induced liver injury," and, "no evidence of clinically significant drug interactions or side effects such as central nervous system, muscle, or renal toxicity." Antisense drugs are DNA-like strands of nucleotides that bind to specific areas of mRNA, called oligonucleotides. This section of gene RNA is then degraded and the corresponding protein is never produced. Therefore, any negative effects of the protein are prevented - similarly to small molecule inhibitors. As they are made of genetic material, it is thought they highly specific compared to small molecule drugs. However, according to Isis, which has heavily invested in antisense development (the majority of its pipeline are antisense drugs), there are at least 12 different ways that mRNA is destroyed and these mechanisms are not fully understood. Happily for Isis, this drug is so far progressing without a problem. The CEO, Dr Stanley Crooke, said: "In the past several months, we have completed important studies in animal models that confirm ISIS 301012 has a unique therapeutic profile. We have also successfully completed long-term toxicology studies." "The data we have presented at ACC underscore and expand ISIS 301012's exciting profile. We look forward to continuing to aggressively and prudently develop this potentially important new drug." Dr William Cromwell, a medical director at the Presbyterian Cardiovascular Institute in North Carolina, US said: "The ability to bring patients to defined lipid goals, coupled with the low risk of drug-induced adverse events seen in these trials, makes ISIS 301012 an exciting potential therapy." Dr Erik Stroes, an investigator on the trials at the University of Amsterdam, Netherlands, said: "The vast majority of patients who have participated in the studies are enthusiastic about Isis-301012. We are already receiving referrals of patients seeking to be included in future studies." Other companies haven't enjoyed such positive results from their antisense programmes. Last December, Genta announced that the US Food and Drug Administration rejected its lead compound, Genasense, as a treatment for chronic lymphocytic leukaemia (CLL). Then, just last week, Genta also announced that it expected the European Medicines Agency (EMEA) to reject the drug as a melanoma treatment - mirroring a decision taken by the FDA in 2004. That decision that prompted Sanofi-Aventis (then Aventis) to pull out of a possible $480m (€366m) collaboration deal. Also, the Canadian pharmaceutical company Methylgene, in conjunction with US-based MGI Pharma, stopped developing MG98 last December. The two companies will seek alternative development partners or arrangements for the second-generation antisense compound, which targeted DNA methyltranseferase.