First Prostate Nanomedicine Shows Positive Results in Phase I Trials
April 4, 2012 -- Researchers at The David H. Koch Institute for Integrative Cancer Research at MIT, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Weill Cornell Medical College and BIND Biosciences have demonstrated for the first time that it is possible to generate nanomedicines targeted against prostate cancers. Acting as “Trojan Horses,” these nanomedicines can navigate directly to malignant cells and concentrate the therapeutic effect of chemotherapy directly in the cancer cells while sparing healthy ones. It is a revolutionary advancement for how complex cancers can someday soon be treated.
This research represents the first time a nanomedicine has moved from the test tube to the clinic to target prostate cancer cells effectively and to deliver docetaxel in high concentrations safely. It was funded in part by a four-year, $5 million Prostate Cancer Foundation (PCF) Challenge Award supported by philanthropist and PCF Board member, David H. Koch, in 2007.
Results from Phase I clinical trials of BIND-014 led by BIND Biosciences with Dr. Omid Farokhzad and Robert Langer, Sc.D., were published today in Science Translational Medicine. These first-in-field data were also presented the today at the 2012 American Association of Cancer Research (AACR) meeting in Chicago. BIND-014 is a programmable nanomedicine that combines a targeting ligand with a therapeutic nanoparticle. BIND-014 contains docetaxel which is encapsulated in FDA-approved, biocompatible and biodegradable polymers.
Docetaxel is a chemotherapy agent which is effective in metastatic prostate cancer alone. It is currently delivered via infusion that floods the body and affects both cancerous and healthy cells, causing significant side effects at doses needed to improve patient survival. By using PSMA targeted nanoparticles to deliver therapeutic treatment, normal healthy cells are widely spared from undesirable treatment side effects.
BIND-014 uniquely targets the prostate-specific membrane antigen (PSMA), a molecule expressed on the cell surface over 95% of all metastatic prostate cancers and also on new blood vessels that feed metastatic growth. In preclinical cancer models, BIND-014 was shown to deliver ten times more docetaxel to tumors than an equivalent dose of docetaxel administered via infusion. The increased accumulation of docetaxel at the site of disease translated to evident antitumor activity on scans and excellent patient tolerability. Studies continue on the first 17 patients treated with BIND-014.
PCF has funded research on PSMA, the attractor antigen or “sticky tape” that is targeted by BIND-014 nanoparticles since 1996. This PCF research further discovered that PSMA is also found on the surfaces of neovasculature (new blood vessels) in the tumors of other cancers.
In designing the nanoparticle, the Langer-Farokzhad team investigated a number of properties that would improve the effectiveness of this new delivery vehicle for antitumor drug drugs. Properties that the team bioengineered included altering the composition of the nanoparticle for “stealth” to slip past the liver or kidneys without damaging either while remaining intact in the bloodstream until they are delivered to and engulfed by the malignant cells. The team also bioengineered an optimum concentration of the chemotherapy agent encapsulated. In fact, Farokhzad, Langer, and colleagues tested over 100 configurations in a process called “systematic parallel screening” of nanoparticles before arriving at the clinical trial configuration, which has prolonged circulation and controlled drug release with plasma concentrations remaining up to more than twenty-fold higher than conventional docetaxel for over 24 hours.
“The development of BIND-014 represents a unique public, private, and philanthropic funding effort to fast-forward and realize the potential of nanomedicines for the benefit of cancer patients,” said Jonathan W. Simons, MD, president and CEO of the Prostate Cancer Foundation. “This is a tour de force of transdisciplinary collaboration—bioengineers, chemical engineers, nanotechnologists, oncologists, and prostate cancer biologists all came together to advance multiple components and concepts to the clinic. Investments by PCF leveraged an early and significant NCI nanotechnology investment in this prostate cancer therapeutics investment. With this exemplary new work across institutional boundaries, BIND-014 represents an entirely new, programmable platform for targeted, cancer drug deliver— and it moved to the clinic in a strikingly short period of time.”
The idea to develop aptamer-targeted nanoparticles to deliver therapeutics was first conceived in 2002 and was advanced rapidly by collaboration between the teams at the four participating cancer research centers.
“These seminal data on BIND’s first clinical stage Accurin, BIND-014, demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated,” commented Omid Farokhzad, M.D., BIND Founder and Associate Professor, Harvard Medical School. “BIND’s data are a giant leap forward in achieving the true promise of nanomedicine by enabling the design of therapeutics with highly-differentiated efficacy and safety that go above and beyond the capabilities of traditional drug design through medicinal chemistry.”
“Previous attempts to develop targeted nanoparticles have not translated into clinical success because of the inherent difficulty of designing and scaling up a particle capable of targeting, long-circulation via immune-response evasion, and controlled drug release,” commented Robert Langer, Sc.D., BIND Founder and David H. Koch Institute Professor at MIT. “BIND-014 is the first therapeutic of its kind to reach clinical evaluation and has demonstrated an increases of up to ten-fold in drug concentration in tumors, which lead to substantially better efficacy and safety.”
With these findings, multiple Phase I/II trials targeting other cancers expressing PSMA can be accelerated safely.