Harnessing the Alzheimer’s Pipeline
Apr05

Harnessing the Alzheimer’s Pipeline

In today’s issue, we have a package about drugs in development to treat Alzheimer’s disease. The main piece looks at the different kinds of drug candidates targeting beta-amyloid, the peptide responsible for the plaques coating the brains of people with Alzheimer’s. Despite a slew of molecules in the later stages of development, there are still questions about whether blocking beta-amyloid accumulation makes the most sense. As the article says: “If the trials are successful—and the amyloid hypothesis is proven true—doctors will have a slew of new drugs that could slow the progression of the disease. If the trials fail, scientists will be forced back to the drawing board to develop new hypotheses and drug targets.” The second piece is a case study of the complicated chemistry campaign involved in developing Merck’s most advanced BACE inhibitor. BACE is an enzyme used to cut down a larger peptide into beta-amyloid, and it has proven to be a tricky target. The last piece asks whether Dimebon, the drug candidate being developed by Medivation and Pfizer, has any legs left in it after it performed miserably in a Phase III trial. The companies say the jury is still out, while most neurologists have less kind words for the drug. Overall, the stories try to harness the pipeline for a market in which big pharma is anxious to have a presence. In its pipeline review at the beginning of the year, Pfizer touted the 10 compounds in development for Alzheimer’s, making it the second only to oncology in terms of therapeutic focus. Bristol-Myers Squibb devoted a good portion of its R&D day last month talking about BMS-708163, its gamma-secretase inhibitor expected to head into Phase III trials later this year. And the number of basic patent filings for Alzheimer’s drugs has jumped from 652 in 2000, to 1995 last year, according to Chemical Abstract Services. Why all the interest? The market is vast and patients are greatly underserved. The two Alzheimer’s drugs currently on the market, Pfizer’s Aricept and Forest Laboratories’ Namenda, are at best mildly effective at temporarily easing the symptoms of the disease. Last year, Pfizer sold $432 million worth of Aricept, while Namenda sales totaled $949 million. With 5.3 Americans suffering from Alzheimer’s, imagine the potential for a drug that actually slowed the disease down. Now factor in the potential for that number of afflicted to quadruple by 2020, and the market for an Alzheimer’s drug starts to look pretty huge. Add in the likelihood that for a drug to have the most effect, it’ll probably need to be given before dementia sets in and for the rest of a person’s...

Read More
Antisoma Adds to Late-Stage Trial Failures
Mar29

Antisoma Adds to Late-Stage Trial Failures

The late-stage drug failures are piling up this month. Today’s news comes from Antisoma and Novartis, which have halted a Phase III trials of ASA404 after it showed no hope of improving the length of survival in patients with non-small cell lung cancer. Novartis shelled out a $75 million upfront payment for the rights to the drug in 2007, and Antisoma was promised nearly a billion dollars more if it reached the market. Novartis picked it up after Roche rejected the drug, licensed through a broad agreement with the British biotech in 2002. There doesn’t seem to be a way forward for ASA404, a small molecule that tried to cut off blood flow to tumors in a more circuitous way then antibodies like Avastin, which block blood vessel growth factors. Antisoma’s shares have already lost over 65% of their value today. Antisoma’s news is the latest in a string of setbacks this month for drugs in mid- to late-stage development. Here’s a little refresher: --Pfizer stopped a Phase III trial of figitumumab, being tested to treat lung cancer, and said Sutent, already approved for treating gastrointestinal stromal tumors, had failed in two, Phase III studies in breast cancer. --AstraZeneca said Recentin, which inhibits all three vascular endothelial growth factor receptors, did not do better than Avastin in a Phase II/III trial in colon cancer patients. --Medivation shares cratered after Dimebon, an Alzheimer’s drug partnered with Pfizer, seemed to do worse than placebo in a Phase III trial. --Roche and Biogen Idec put on hold its development program for ocrelizumab, in studies to treat rheumatoid arthritis and lupus, after a safety board said the risks seemed to outweigh the benefits. --Genmab’s stock tanked after reporting zalutumumab did not show enough improvement in survival in patients with head and neck cancer in a Phase III trial. --Actelion’s bosentan, a dual endothelin receptor antagonist, failed in a Phase III trial in idiopathic pulmonary fibrosis Have I missed any? Post them in the comments! Update! GenVec said this evening that it was discontinuing a Phase III of TNFerade in patients with pancreatic...

Read More