Prothena revives amyloidosis program nearly 3 years after flop

 Prothena canned its AL amyloidosis program in 2018 after it failed a midstage trial and a data monitoring committee deemed a separate phase 3 study doomed to fail. Now, the biotech is resurrecting the program after an analysis of the phase 3 data found the drug helped the sickest patients live longer.

That study, dubbed VITAL, tested the drug, known as birtamimab or NEOD001, against the standard of care in 269 patients with AL amyloidosis, short for amyloid light-chain amyloidosis. After terminating the study for futility, Prothena crunched the data and found that the sickest patients—those whose disease was classed as Mayo stage 4 at the start of the study—did significantly better on birtamimab than on placebo.

At the nine-month mark, the analysis found nearly three-quarters of the sickest patients on birtamimab were still alive compared to about half of the sickest patients taking placebo (74% versus 49%). Granted, these numbers are from just 77 patients, or 30% of the total patients in the trial, but they’ve convinced Prothena and the FDA that there is a future for this drug in these patients.

Under a Special Protocol Assessment agreement with the FDA, Prothena company will kick off a new phase 3 study in mid-2021. It will test the drug, known as birtamimab or NEOD001, in patients with Mayo stage 4 AL amyloidosis. The disease is similar to multiple myeloma in that it stems from dysfunctional plasma cells in the bone marrow. They produce an abnormal version of light chain, a protein that makes up antibodies.

“The normal job of immunoglobulin light chain is to combine with heavy chain to make immunoglobulins, or antibodies,” said Prothena CEO Gene Kinney, Ph.D. The abnormal light chain proteins don’t bind properly with the heavy chain proteins, fold incorrectly and build up in various tissues, most notably in the heart. Over time, this buildup can lead to life-threatening problems, including heart and kidney failure.

“When we talk about Stage IV patients—if we look to the literature—the predicted median survival of those patients is somewhere around six months following diagnosis,” Kinney said.

The standard of care includes chemotherapy and cell-killing drugs that were originally developed for multiple myeloma. These treatments focus on eliminating abnormal plasma cells and reducing the amount of disease-causing protein they produce.

“The limitation is probably obvious for patients who already have an appreciable amount of protein deposition in vital organs,” Kinney said. “It’s essentially turning off the faucet once the bathtub is full.”

Prothena hopes that adding its drug to those already in use will help the sickest patients recover organ function and live longer.

The new phase 3 study, known as AFFIRM-AL, will test birtamimab in 260 patients with AL amyloidosis affecting their heart and who have never been treated. Two-thirds of the patients will receive birtamimab, while the remaining third will receive the standard of care. The primary endpoint is death from any cause. The plan is to conduct an interim analysis when about half of the patients in the study have died, at which point an independent data monitoring committee will recommend it either continue or be stopped for overwhelming efficacy, the company said in a statement.

https://www.fiercebiotech.com/biotech/prothena-revives-amyloidosis-program-nearly-3-years-after-flop