A signature research project of the Mayo Clinic’s Center for Regenerative Medicine – using stem cells to treat ischemic heart failure – has proven effective on enough patients in a European clinical trial to prompt its corporate backer to accelerate commercialization efforts.
 
The results, announced last week, heralded the first time heart cell regeneration has been shown effective in a large-scale trial and could represent a major win for the Mayo center, which began work on the concept a decade ago.
 
The product, C-Cure, is being developed by the Belgian company Celyad S.A. under an exclusive license from Mayo. Touted as a potential paradigm-shifter in treating the dire condition, the technique was co-developed by Dr. Andre Terzic, director of the Rochester clinic’s regenerative medicine center, as one of its first big projects.
 
Celyad, formerly known as Cardio3 Biosciences, obtained the know-how in 2007 and is now in its third phase of clinical testing for C-Cure, which uses a proprietary protein “cocktail” to turn a patient’s undifferentiated stem cells into “smart stem cells” that can regenerate dying heart tissue when placed back into the organ.
 
The company and Mayo believe the technology will ultimately shift the focus in treating ischemic heart failure (HF) away from mainly just managing an often-fatal condition to one of early intervention and organ regeneration.
 
Approximately 5.7 million patients were diagnosed with HF in the United States in 2012. An alternative treatment is urgently needed because while existing therapies have been somewhat effective, the long-term prognosis associated with HF is dire – it carries a 50 percent mortality rate at five years following initial diagnosis. Regenerative medicine seeks to address this by replacing or repairing non-functioning myocytes, or heart cells, which as they die lead to loss of cardiac function.
 
The long effort to secure approvals for C-Cure and bring it to the market has already included two clinical trials, including a Phase II human trial that was completed in 2012. That same year, the first of a two-part Phase III trial was launched – a 240-patient study in Europe and Israel (called CHART-1), aimed at HF patients to determine if stem cell therapy could improve their mortality rates, quality of life and a set of other measures.
 
Last week, Celyad announced that while the results of CHART-1 did not show an across-the-board statistical difference in comparison to a control group, they did produce “clearly identifiable positive trends” for the entire population.
 
But most importantly, they also showed a statistically significant improvement for a subset of 60 percent of the enrollees, who were classified by the volume of blood their hearts were capable of pumping before the trial. Celyad said the results within that group were strong in all of the endpoints measured: mortality, worsening heart failure events, quality of life, six-minute walking test, blood volume and ejection fraction.
 
“The results seen for a large clinically relevant number of the patients are groundbreaking,” said Jozef Bartunek, a researcher with OLV Hospital in Belgium and leader of the CHART-1 study. He added it would allow researchers to focus on their efforts on those types of HF patients in the upcoming second and pivotal Phase III trial (CHART-2), which is to be conducted in the United States.
 
Celyad CEO Christian Homsy said the CHART-1 results means the firm will move forward with seeking European market approvals for C-Cure, and along with that move, begin a search for commercialization partners.
 
“CHART-1 has allowed us to better define the patient population that would benefit from C-Cure,” Homsy said. “We are excited by the prospects for C-Cure as a new potential treatment option for a highly relevant heart failure population. We are confident that the results will generate interest from potential partners that could accelerate the development and commercialization of C-Cure.”
 
The relationship between Mayo’s Center for Regenerative Medicine and Celyad is a close one, going back at least nine years. They further cemented it in 2014 with the signing of a “preferred access agreement,” under which Celyad gets first shot at any new regenerative medicine technologies developed by the center until 2017.
 
Until this year, the Belgian firm was set to establish a prototype laboratory in Rochester, leasing 15,000 square feet in the city-owned Minnesota BioBusiness Center. But it ultimately chose not to proceed, citing higher-than-expected development costs.
 
Despite that disappointment, Mayo’s financial and research ties with Celyad remain. In addition to the more than $13.3 million in upfront payments the clinic has received for Dr. Terzic’s know-how since 2007 (some of which has been converted to stock), it has a “low-single-digit” royalty deal for C-Cure in place, which could ultimate prove very lucrative.