FoldRx Pharmaceuticals Announces Positive Results from Pivotal Phase II/III Clinical Study of Tafamidis

Tafamidis significantly halts disease progression and reduces burden of disease in patients with TTR amyloid polyneuropathy

23-Jul-2009 - USA

FoldRx Pharmaceuticals, Inc. announced positive results from its pivotal Phase II/III clinical study of the company’s lead compound, tafamidis (Fx-1006A), in patients suffering from TTR amyloid polyneuropathy (ATTR-PN), a fatal orphan disease also known as Familial Amyloid Polyneuropathy (FAP). Liver transplantation is the only currently available treatment option for this progressive neurodegenerative disease. Preliminary results from the first randomized controlled trial ever completed in this disease demonstrate that tafamidis treatment significantly halts disease progression in ATTR-PN, reduces the burden of disease after 18 months compared to placebo, and appears to be safe and well-tolerated.

In the evaluable population, which includes all patients who completed the study per protocol, statistical significance was achieved for both primary endpoints -- disease progression as measured by the Neuropathy Impairment Score - Lower Limb (NIS-LL), and quality of life as measured by the Norfolk Quality Of Life (QOL) (p=0.041 and p=0.045, respectively). No disease progression was observed in 60% of tafamidis patients as compared to 38% of placebo patients after 18 months treatment. In addition, there was a significant deterioration in QOL in placebo patients compared to those treated with tafamidis after 18 months.

A factor in this trial was the appropriate evaluation of treatment response in patients undergoing liver transplantation. In the intent to treat population, where liver transplant patients were treated as non-responders, there was a clinically meaningful difference between the treatment groups as measured by the NIS-LL (p=0.068) and Norfolk (p=0.12). In an alternative, prospectively defined analysis that adjusted for the impact of liver transplantation, statistical significance was achieved (p=0.039).

In addition, a number of secondary endpoints, including objective measures of disease severity and nerve function corroborate the treatment effect seen in the primary endpoints, with tafamidis treatment resulting in statistically significant and clinically meaningful improvements when compared with placebo.

“The consistency of the results across the various endpoints and analyses clearly demonstrate the robust effect of tafamidis in halting disease progression in ATTR-PN,” noted Richard Labaudinière, Ph.D., President and CEO of FoldRx. “If approved, tafamidis would be the first disease modifying agent targeting protein misfolding. We plan discussions with the U.S. and European regulatory agencies later this year and we anticipate filing marketing applications in 2010.”

In patients with ATTR-PN, amyloid fibrils, caused by the “misfolding” of a protein called transthyretin (TTR), are deposited in peripheral nerve tissues that serve limbs and organs. Tafamidis has been shown to act as a pharmacological chaperone for TTR, preventing the misfolding of the TTR protein, thus preventing the further accumulation of the amyloid fibrils on nerve tissue and protecting the patient from loss of nerve function.

“These results demonstrate that tafamidis positively alters the neurological deterioration characteristic of this disease and was well-tolerated,” said Teresa Coelho, M.D., Hospital Santo Antonio in Porto, Portugal, a principal investigator in the study and one of the worldwide experts on the disease. “ATTR-PN is a slowly progressive neurodegenerative disease that causes loss of sensation, muscle weakness and autonomic nerve dysfunction, ultimately leading to death. Tafamidis has the promise of being the first disease-modifying pharmacological therapy for ATTR-PN and offers new hope for patients suffering from this life threatening disease. Physicians will welcome this once-daily, oral treatment as an alternative to liver transplantation.”

https://www.bionity.com/en/news/103676/foldrx-pharmaceuticals-announces-positive-results-from-pivotal-phase-ii-iii-clinical-study-of-tafamidis.html