Currently, the FDA is evaluating 2 investigational drugs, both of which treat the underlying pathophysiology of hereditary transthyretin amyloidosis.
The Institute for Clinical and Economic Review (ICER), a body that performs analyses on the effectiveness and costs of medical treatments and develops reports assessing the value of key new drugs, has requested public comment on inotersen and patisiran, 2 therapies that treat hereditary transthyretin (hATTR) amyloidosis.
A rare, progressive, and fatal condition, hATTR amyloidosis is caused by genetic mutations that cause deposits of transthyretin (TTR), a protein present in human serum, in body tissues. These deposits produce sensorimotor disturbances as well as autonomic, cardiovascular, gastrointestinal, renal, leptomeningeal, bowel, and bladder dysfunction. Patients who are not treated die approximately 10 years from disease onset.
No treatments are available to reverse the damage caused by TTR deposits, but some treatments—such as liver transplantation, the off-label use of the nonsteroidal anti-inflammatory drug diflunisal, or the use of a TTR stabilizer (not available in the US market)—can help to delay disease progression. However, these treatments have limited efficacy.
Currently the FDA is evaluating 2 investigational drugs, both of which treat the underlying pathophysiology of hATTR amyloidosis. The first agent, inotersen, developed by Ionis Pharmaceuticals, is an antisense oligonucleotide that complements the messenger RNA that encodes for TTR. Administered subcutaneously once per week, inotersen binds to the messenger RNA and degrades TTR. The second agent, patisiran, developed by Alnylam Pharmaceuticals, is an RNA interference therapeutic delivered by intravenous infusion. The drug suppresses the production of both mutant and nonmutant forms of TTR. In phase 3 trials, both of the drugs improved neuropathy impairment, the main study outcome.
In ICER’s draft scoping document, the organization says that the comparator treatments used in its evidence review of the 2 drugs will be placebo (which was used in clinical trials) and, data permitting, diflunisal. Treatment effectiveness will be estimated using published estimates and, potentially, meta-analysis of published evidence. In the complementary economic evaluation, ICER will assess the cost-effectiveness of the 2 drugs relative to conventional support therapy. In a separate analysis, ICER will explore the health system budgetary impact of treatment over a 5-year time horizon, which will allow for assessment of any need to manage the cost of these interventions.
The scoping document, according to ICER, was developed with input from a variety of stakeholders, and members of the public—including patients—may submit comments on the document.