Pharm Exec's 2012 Pipeline Report - Pharmaceutical Executive


Pharm Exec's 2012 Pipeline Report

Pharmaceutical Executive

Alzheimer's Disease: Still Waiting

Even the Republican presidential candidates are talking about a cure for Alzheimer's disease, but like most everyone else, they're just diagnosing the problem. Newt Gingrich and Jon Huntsman think NIH should spend more than $450 million a year on Alzheimer's research. Mitt Romney says funding should be determined by mortality rates. Rick Perry sees promise in stem cells for Alzheimer's, and Michelle Bachmann declared on her healthcare website that "as President, I will work to unleash the power of medical innovation ... because a cure is always better and cheaper than care."

Still, no disease-modifying treatments, or any decent treatments at all, have emerged for the roughly 26 million people affected by Alzheimer's disease globally. Later-stage clinical trials are long and arduous, and are carefully regulated, although a group of industry experts and researchers were able to convince FDA to loosen up on some the of rules last July. After Pfizer and Johnson & Johnson's bapineuzumab caused brain swelling in some trial patients, FDA initially issued stricter guidelines, but has since relaxed them, in recognition of the need for a drug. J&J launched a program called "Healthy Minds" in November, a collaborative affair with $3 billion in seed money, in the hope of combating Alzheimer's through better communication and data networking. The program is a supplement to the International Mental Health Research Organization's "One Mind for Research" program. Lilly's solanezumab, a drug that also targets amyloids, is expected to conclude two identical 18-month, 1,000-patient (with mild to moderate Alzheimer's) trials, called Expedition and Expedition-2, in the first half of 2012.

"Alzheimer's disease, like Parkinson's, is a tough nut to crack," says Geller, but companies have a wide-open market that's ripe for the taking. Alzheimer's is "high risk, high reward," says Weintraub, "but if it does work, it's going to be huge."

iRNA: Curbing Rogue Cells

Small interfering RNA (iRNA), deployed as a therapeutic, could potentially cure cancer. That's a long shot, sure, but it's not inconceivable. So far, no iRNA therapy has progressed past Phase II of development, but some interesting data has been floating around certain corners of the industry, and the Web, as of late.

At a November conference in Japan, Alnylam Pharmaceuticals, a leader in the category (with two iRNA treatments in Phase II), announced positive preliminary results from a Phase I trial on ALN TTRO1, an iRNA therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis, a protein buildup in tissues. All five patients tested responded to the treatment; the group showed lowering of serum TTR protein that ranged from 25 percent to 81 percent (a statistically significant mean of 41 percent) after a single dose, and there were no side effects, beyond minor infusion reactions (13 percent of patients). What does all this mean? For the first time, an iRNA treatment has silenced a disease-causing gene in a clinical trial.

D'vorah Graeser, CEO of Graeser Associates International, a healthcare IP firm, explains iRNA therapies as blockers; they are developed synthetically, and then sent into the body to connect to messenger RNAs (or mRNAs) in cells that have gone rogue. Adjusting the mRNA tones down the protein that's being expressed. "Many times one particular part of the cell's process has gone haywire in cancer, and if you can block one protein from being expressed, then you can hopefully cure cancer," says Graeser. Interfering RNAs are extremely targeted, and could be applicable to whole categories of cancer that have a common mechanism. "Instead of treating cancer according to where in the body it originated, it could be treated by targeting the general mechanism, which has been identified for that particular cancer type," says Graeser.

Alnylam holds patents on delivery mechanisms, which range from particle injections and iRNA coated with liposomes that have a hydrophobic end, like a little cell, to conjugates, or other molecules chemically linked to small iRNA, which help it survive in the body and enter the cell. "For cancer, you'd need something that can survive systemically, and that is a problem," says Graeser. Nevertheless, Alnylam has an iRNA therapy in Phase I for liver cancer, and the company is looking for a partner for Phase II. The company has formed alliances with Roche and Takeda, and has licensing deals with Novartis, Cubist, Biogen Idec and others. Alnylam announced its 5x15 program in January, which "establishes a path for development and commercialization of novel iRNA therapeutics to address genetically defined diseases with high unmet need." The company expects to have five iRNA therapeutic programs in advanced clinical development by 2015.


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