Prothena reveals positive amyloidosis data; CEO's cancer
This article was originally published in Scrip
Elan spinout Prothena said after the stock market closed on 2 December that interim Phase I/II results for NEOD001 in the treatment of amyloidosis justify initiation of a Phase III clinical trial, but the company's stock closed down 5% at $21.99 on 3 December after CEO Dale Schenk revealed that he has pancreatic cancer.
Dr Schenk said in a 2 December letter to Prothena employees that his cancer was diagnosed early and he recently had a successful surgery to remove the tumor and part of his pancreas. While the cancer appeared to be confined to the surgery site, an evaluation of his condition and determination of his treatment plan is ongoing. Dr Schenk said his activity will be somewhat limited by his recovery from surgery, but he will remain actively involved in the company.
"I feel very good and optimistic. I believe that my personal background as a scientist is particularly helpful and beneficial in approaching this personal challenge," Dr Schenk wrote.
He served as Elan's chief scientific officer before the Irish company, now owned by Perrigo, spun Prothena out as a separate entity at the end of 2012 (scripintelligence.com, 30 January and 29 July 2013).
Despite the positive Phase I/II readout for NEOD001 and the Prothena CEO's optimistic outlook about his diagnosis, the company's market cap dropped to $602.2m and its stock is trading toward the low end of its $16.71 to $49.24 price range since Prothena's June initial public offering in the US at $22.50 per share (scripintelligence.com, 30 June 2014).
The company's lead development programs NEOD001 for amyloidosis and the Roche-partnered PRX002 for Parkinson's disease are in Phase I development (scripintelligence.com, 12 December 2013). PRX003 for psoriasis is expected to enter the clinic in 2015.
NEOD001 results
Prothena initiated the Phase III VITAL Amyloidosis Study based on results from the ongoing Phase I/II clinical trial for NEOD001 in patients with AL amyloidosis and persistent organ dysfunction.
Systemic amyloidoses are progressive diseases caused by tissue deposition of misfolded amyloid proteins that result in progressive organ damage. AL amyloidosis, the most common form of the disease, involves a hematological disorder caused by plasma cells.
Prothena chief scientific officer Gene Kinney said in a statement regarding the Phase I/II results: "we believe the robust 50% cardiac and 42.9% renal best response rates in patients treated with NEOD001 compare favorably with historical data that would have predicted 26.5% cardiac and approximately 24% renal response rates in patients treated solely with off-label standard of care."
The expansion stage of the Phase I/II study is enrolling up to 25 additional patients from which the company expects to report initial results in 2015 and annually thereafter.
Seven out of 14 evaluable patients (50%) who were treated with monthly infusions of NEOD001 during the dose-escalating stage of the Phase I/II study demonstrated a cardiac response, which was defined as a more than 30% and 300pg/mL decrease in levels of NT-proBNP, a validated cardiac biomarker associated with mortality.
Six of 14 evaluable patients (42.9%) demonstrated a renal response, which was defined as a 30% decrease in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening.
NEOD001 has been generally safe and well-tolerated in the Phase I/II clinical trial with mild to moderate fatigue, cough, dyspnea, diarrhea, upper respiratory infection, anemia, headache, hyponatremia, nausea and edema as the most common side effects.
No dose-limiting toxicities have been observed and 24mg/kg was selected as the monthly dose to be tested in Phase III. Nineteen out of 27 patients in the Phase I/II study continue on therapy as of 30 September, but none of the eight patients who discontinued treatment did so due to drug-related adverse events.
The placebo-controlled Phase III study will enroll 230 newly-diagnosed AL amyloidosis patients. The clinical trial's event-based primary endpoint is a composite of all-cause mortality and cardiac hospitalizations. Secondary endpoints include cardiac and renal biomarkers, six-minute walk test, and quality of life evaluations.
Sagient Research gives NEOD001 a 62% likelihood of US FDA approval (LOA), which is the average LOA for drugs in similar indications and stages of development.