By Mark Terry


Prothena Corporation, headquartered in Dublin, Ireland, announced it had shuttered its NEOD001 program for AL amyloidosis after the failure of its Phase IIb PRONTO study and Phase III VITAL study. Shares dropped 60 percent in premarket trading at the news.

The Phase IIb trial did not meet its primary or secondary endpoints. Prothena then asked an independent data monitoring committee (DMC) to review the futility of the Phase III VITAL trial. The committee recommended discontinuing the VITAL study. As a result, Prothena executives decided to discontinue all development.

“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, president and chief executive officer of Prothena, in a statement. “We are surprised by the results from these two placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical and advocacy communities. We thank all of the patients, their families, caregivers, investigators, study staff and our employees. Their participation in and commitment to these studies are indispensable to advancing our shared goal of improving the lives of patients with amyloidosis.”

AL amyloidosis is the most common type of systemic amyloidosis. These are a group of diseases caused by the accumulation of misfolded proteins in tissues that leads to progressive organ damage. AL amyloidosis is a rare, progressive, and typically fatal illness caused by extracellular accumulation of misfolded immunoglobulin light chains.  It leads to widespread organ failure, including heart, kidneys, and nervous system.

At one point, analysts had projected the drug might have peak sales of $1.5 billion. The drop in company shares almost halved the company’s $1.4 billion market cap, knocking more than $775 million out of its value.

The endpoint of the Phase IIb PRONTO trial was a measurement of cardiac best response evaluating a biomarker for NT-proBNP. No statistically significant differences were seen between treatment groups. The cardiac best response in the NEOD001 group was 39.4 percent and in the placebo group 47.6 percent.

Although momentarily disastrous for the company and investors, on March 20, Prothena signed a global collaboration deal with Celgene to develop new therapies for a range of neurodegenerative diseases. It focuses on three proteins connected to several neurodegenerative diseases, including tau, TDP-43 and an undisclosed third target. They are implicated in Alzheimer’s disease, progressive supranuclear palsy, dementias, amyotrophic lateral sclerosis and other diseases.

Celgene picked up exclusive righs to license clinical candidates in the U.S. for each of the programs when the investigational new drug (IND) is filed. If they opt for those, they would also have the right to expand the license to global rights at the completion of Phase I trials. After that, Celgene will be responsible for funding all further global development and commercialization. Prothena received $100 million upfront and a $50 million equity investment, as well as future potential exercise payments and regulatory and commercial milestones for each program. Prothena will also be eligible for royalties on net sales of any marketed products.

“We are excited to be working with Celgene, a leading global biopharmaceutical company with deep expertise in targeting critical biological pathways involved in protein homeostasis and an extensive track record of successfully bringing forward innovative new therapies based on this biology,” Kinney said in a statement at the time. “As we build our pipeline of novel therapies across the neuroscience and orphan disease categories, this collaboration provides Prothena the opportunity to work with a premier scientific partner and the resources and flexibility to advance these programs while continuing to expand our proprietary discovery activities and further supports our efforts to deliver a diversified pipeline of therapies to alter the course of devastating diseases.”



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