West Coast Editor
FoldRx Pharmaceuticals Inc. started the Phase II/III study with Fx-1006A for the first niche disease targeted - familial amyloid polyneuropathy, a fatal genetic disorder that afflicts about 10,000 people worldwide.
Richard Labaudinière, president and CEO of Cambridge, Mass.-based FoldRx, said the firm expects to have data from the trial by 2009, and to file for approval shortly thereafter.
"This will be one of the first examples of an oral drug to correct protein misfolding and stop disease progression," he said, noting that the company has a separate, yeast-based platform developed from work done by Susan Lindquist, professor at the Massachusetts Institute of Technology.
The trial will test oral Fx1006A in 120 patients with FAP and a confirmed V30M transthyretin (TTR), which is the most prevalent disease variant.
Subjects will get 18 months of once-per-day treatment, and co-primary endpoints will measure response at 18 months via the Neuropathy Impairment Score-Lower Limb (NIS-LL, done by physical exam), along with quality of life, as gauged by the Norfolk QOL-DN, often used to weigh patients' perceived response to treatment for neuropathy.
FoldRx went after FAP first because the disease is well understood and resembles, at least somewhat, the diabetic form - though not in terms of severity. FAP, sometimes called Corino de Andrade's disease (after the Portuguese neurologist who first identified it), kills in seven years to 10 years after diagnosis.
"It's a very dramatic disease," Labaudinière said.
Amyloid fibrils caused by misfolded TTR build up in peripheral nerve tissues that serve the limbs and organs. Those afflicted with the painful ailment steadily lose sensation and motor function, and their organs fail.
Patients have no options except for a liver transplant. Fx-1006A is designed to stop FAP's progression by blocking the accumulation of fibrils.
After FAP, FoldRx will try Fx-1006A against familial amyloid cardiomyopathy, another TTR condition, which hits about 125,000 people in the U.S., with the mutation cropping up in about 4 percent of African Americans.
The company also is working on a molecule to treat Parkinson's disease by preventing the misfolding of the alpha-synuclein protein.
"Eventually for Parkinson's we will have to look for a partner, but for the other programs, we think we can do it on our own or through a partnership with some foundation for rare disease," Labaudinière told BioWorld Today.
FoldRx raised $43 million in a Series B round about a year ago, and the firm has enough cash on hand to finish the Phase II/III trial, he added. (See BioWorld Today, May 31, 2006.)
Labaudinière's background includes management positions at London-based GlaxoSmithKline plc and Aventis SA (now the Sanofi-Aventis Group, of Paris).
He has biotech experience, too. With Genome Therapeutics Corp. (now Oscient Pharmaceuticals Corp.), he oversaw development of the lead candidate, Ramoplanin, for serious hospital-based infections, while managing deals with pharma in the fields of osteoporosis, asthma and infectious diseases.
Companies with a Parkinson's interest making news lately include Biogen Idec Inc., of Cambridge, Mass., and partner Vernalis plc, of Winnersh, UK, who began Phase II testing this month with BIIB014, also known as V2006, an oral adenosine A2A receptor antagonist.
But the most notorious illness in which protein misfolding causes trouble is Alzheimer's disease, in which clumps of aberrant amyloid beta protein, known as amyloid plaques, disrupt the brain.
Dublin, Ireland-based Elan Corp plc and collaborator Wyeth, of Madison, N.J., said they soon will start Phase III testing with bapineuzumab (AAB-001), which targets amyloid beta, for mild to moderate Alzheimer's disease later this year. (See BioWorld Today, May 22, 2007.)
Another firm investigating misfolded proteins is Cranbury, N.J.-based Amicus Therapeutics Inc., which this spring - six months after withdrawing an earlier bid - filed again for an initial public offering, hoping to raise $86.3 million to fund ongoing development of its lead drugs against lysosomal storage disorders. (See BioWorld Today, April 2, 2007.)
FoldRx plans to cast a wider net, too. "With yeast, we can tackle not only Parkinson's disease but what we call the loss-of-function diseases, where you have a loss of trafficking of the protein," as in the case of cystic fibrosis and the LSDs, Labaudinière said.
The firm has 23 employees and expects to hire more.