As promised, we are continuing to provide coverage of newly announced or recently discovered collaborations between industry, academia, and other entities to highlight the importance of such relationships in furthering medical progress and improving patient care.   

Michael J. Fox Foundation and Parkinson’s

A recent opinion article published in Nature Medicine discussed how “Money without collaboration won’t bring cures.”  The piece, written by Todd B. Sherer, chief executive officer of The Michael J. Fox Foundation for Parkinson’s Research, maintained that “It’s up to stakeholders at every stage of therapeutic development—industry and academic researchers, policymakers, patient foundations and even patients themselves—to embrace the power of collaboration.  Only then will we enable translational research and push much-needed treatments to the clinic faster.” 

Sherer noted that he attended the inaugural meeting of NCATS, of which he is charter member. While noting the honor of serving on the council, he asserted that “government efforts to kickstart drug development will not be enough to bridge the divide between the basic research typically conducted by academic institutions and the large-scale clinical studies orchestrated by the pharmaceutical industry.”  

Rather, he recognized that “it is the shared responsibility of all of us involved in every stage of drug development—at any phase, in the public or private sector—to contribute to filling this gap.”  Using his experience at the Michael J. Fox Foundation (MJFF), Sherer said he has seen first hand “how this approach can pay off.”    

“We’ve seen how collaborations among academic and industry players are ignited when researchers share information in real time, how meeting scientists’ needs for better research tools enables them to move toward breakthroughs faster and how investing in early promising therapeutic targets is crucial.  Despite the inherent risks involved in these efforts, the reward could be the cure that countless patients don’t have the time to wait for.” 

The foundation’s “exclusive mission is to accelerate the development of a cure for Parkinson’s disease, and over 90% of [their] funding is allocated to the translational and clinical research closest or most essential to patient relevance.”  Thus far, the foundation has approximately $300 million in research to date, something Sherer called “chump change in the context of the therapeutic development ecosystem.” 

Nevertheless, he noted that due to the foundation’s “strategic investments and untraditional collaborations with industry partners,” they have “seen seismic shifts in the Parkinson’s therapeutic development landscape over the past decade, with major progress toward improved symptomatic and disease-modifying therapies alike.”   

Accordingly, Sherer asserted that “Strategic investments in translation and collaboration can pay off,” and the MJFF has seen firsthand how strategic investments in translation and collaboration can pay off.  For example, a new partnership between Vanderbilt University and Bristol-Myers Squibb (BMS) leverages investments MJFF has been making in Vanderbilt since 2005. The Tennessee-based institution’s Center for Neuroscience Drug Discovery, with MJFF’s funding, has been working to develop a new glutamate-based class of symptomatic treatment for Parkinson’s disease.  Following proof of concept in rodent models, this work has now ripened to readiness for major follow-on funding from BMS. It’s a win for our foundation, Vanderbilt, BMS and, most importantly, patients with Parkinson’s. 

Sherer further explained his role in the US Presidential Council of Advisors on Science and Technology (PCAST) on the need for widespread, public-private collaboration to propel innovation in drug discovery and development and to be part of a panel discussion on implementing PCAST’s recommendations.  He also noted the formation of TransCelerate BioPharma, a nonprofit organization that means to take a collaborative, precompetitive approach to accelerate the development of new drugs.  

Given these announcements Sherer was “energized by the prospect of greater resources and a new framework for collaborations focused on problem-solving in the translational space, especially when today’s scientists have so many promising new avenues for investigation, new targets for therapies and rapidly advancing technologies—crucial tools for progress that the field didn’t know about, or that didn’t exist, ten years ago.” 

The promise of collaboration goes beyond Parkinson’s.  For example, Sherer noted how the progress enabled by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a collaborative effort among multiple groups including government, drug companies, universities and nonprofits, “has galvanized drug development for that disease in relatively few years Alzheimer’s drugmakers have taken the proactive step of pooling data from those trials in an attempt at problem-solving and increasing the odds of better future results.”  The foundation’s “own Parkinson’s Progression Markers Initiative, supported by 13 pharmaceutical funding partners, has benefited from having ADNI as a scientific precedent and a successful model of collaboration.” 

The Fox Foundation executive also highlighted the critical role patients are playing, for example, through the use of MJFF’s Fox Trial Finder, an online tool that combines matches volunteers to trials on the basis of several factors (including geography, treatment history and individual preference) and allows for anonymous two-way messaging between volunteers and clinical trial teams, has exploded since its launch by our foundation in April 2012.  More than 12,000 registrants have signed up to date.  

Despite all this success, Sherer acknowledged the need for more volunteers, and greater resources to educate patients and their loved ones about the vital part that only they can play to keep research moving forward.  Ultimately, he expressed his hope that through collaboration, “we can make cures inevitable.” 

Bayer Supports Innovative Drug Discovery in Europe  

In early February of this year, Bayer Healthcare announced that it would initiate and coordinate a newly founded pan-European consortium, named European Lead Factory, which has been launched to enhance early drug discovery addressing the need for innovative drugs.  The new five-year project will create an exceptional small molecule library collection allowing drug discovery on innovative and promising targets from pharma companies and academia.  

Bayer HealthCare and six other pharmaceutical companies, all members of the European Federation of Pharmaceutical Industries and Associations (EFPIA), will collectively contribute at least 300,000 substances to the European Lead Factory initiative.  The other 6 major drugmakers include AstraZeneca, Lundbeck, Janssen, Merck KGaA, Sanofi, and UCB Pharma.  Together the companies are pooling 196 million euros ($265 million) for this new collaboration.  Bayer said it will provide about 50,000 compounds. 

Additionally, a library of estimated 200,000 compounds will be newly developed jointly by academia and Small and Medium Enterprises (SMEs) in the course of the new initiative. Together, the two libraries will form a Joint European Compound Collection consisting of up to half a million compounds that will be accessible not only to all project partners, but also to public organizations and SMEs who are invited to introduce promising new targets for pharmacological screening. Target proposals will be selected through competitive calls. Thus, drug discovery using the Joint European Compound Collection will be performed on proposed targets from pharma companies as well as targets sourced from the public domain.

The consortium will also set up a state of the art European Screening Centre with compound logistics and High Throughput Screening (HTS) facilities which will be located in Scotland and The Netherlands respectively. The highly-automated process will allow researchers to rapidly screen the exceptional Joint European Compound Collection for molecules that could be a promising starting point in the development of new drugs.

“The European Lead Factory is an outstanding example of a project in which public-private partnerships enable collaborative drug discovery”, said Hanno Wild, Senior Vice President and Head of Candidate Generation & Exploration at Bayer HealthCare Global Drug Discovery. “The platform brings together academia and industry as well as Small and Medium Enterprises in a unique partnership aiming to discover innovative medicines. Bayer is committed to further develop this novel platform by providing decades of experience in drug development. The joint efforts of the consortium will support drug discovery and hopefully generate new therapies for patients.”

“It’s a big change for companies because their compound libraries have usually been kept very secret,” said Ton Rijnders to Reuters, scientific director of Dutch non-profit group TI Pharma, who is helping to run the project.  “They are doing this because it is cheaper than building ever larger libraries on their own – and partnering with academics gives them access to innovative ideas.”

The novel consortium is a public-private partnership supported by Europe’s Innovative Medicines Initiative (IMI), the world’s largest public-private partnership in health.  The Innovative Medicines Initiative currently supports 40 projects, many of which are already producing impressive results. The projects all address major bottlenecks in drug development, and so will accelerate the development of safer and more effective treatments for patients.

Michel Goldman, IMI Executive Director, said: “IMI is very excited by the launch of the European Lead Factory. This unique project is an excellent example of how a public-private partnership can transform the way in which the pharmaceutical sector identifies new medicines. For the first time, it will give European researchers unprecedented access to industry chemical collections and facilitate the translation of their findings into actual treatments for patients. This project will not only advance the chances of success in the discovery of new medicines by European researchers, but also add value by building research capacity in Europe.”

The European Lead Factory consists of 30 international partners, including pharmaceutical companies, SMEs and academia. This new public-private partnership has been initiated for a period of five years. Based on the proven success of the open innovation model, the European Screening Centre and the teams of SMEs and academic institutions aim for a sustainable role in drug discovery and the future growth of drug development in Europe after the initial funding period.  

The total budget for the project amounts to around €196 million. Up to €80 million comes from the European Commission’s Seventh Framework Programme for Research (FP7), and about €91 million is provided as in kind contributions from the participating EFPIA companies. The remaining €25 million comes from other contributions from the non-EFPIA participants. 

Avastin Significantly Improves Survival for patients with recurrent and metastatic cervical cancer 

In addition to the recent collaboration, NIH recently announced that “Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis of a large, randomized clinical trial.” 

It is estimated that over 12,000 women will be diagnosed with cervical cancer in the United States in 2013 and over 4,000 women will die of the disease.

The clinical trial, known as GOG240, was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the Gynecological Oncology Group (GOG).  Genentech, Inc., South San Francisco, Calif., the drug manufacturer, provided support for the trial under the Cooperative Research and Development Agreement (CRADA) with NCI for the clinical development of bevacizumab.  

The data safety monitoring committee overseeing the trial recommended that the results of a recent interim analysis be made public because the study had met its primary endpoint of demonstrating improved overall survival in patients who received bevacizumab, which also means that it delayed the chance of dying from the disease.  

Patients who received bevacizumab got a dose of 15 milligrams per kilogram (mg/kg) of body weight administered in the vein with their chemotherapy treatment and continued with this dose one day every three weeks until disease progression or unacceptable toxicity occurred.  Those patients lived a median 3.7 months longer than those who did not receive bevacizumab. Patients treated with chemotherapy alone had a median survival of 13.3 months while those who received chemotherapy and bevacizumab had a median survival of 17 months. This survival difference was highly statistically significant. However, patients receiving bevacizumab experienced more side effects than those who did not. These side effects were consistent with side effects previously known to be associated with bevacizumab. 

“The findings in this clinical trial are important because they are likely to change clinical practice and provide an opportunity to improve outcome in patients with recurrent cervical cancer who have previously had very limited treatment options,” said GOG study chair Krishnansu S. Tewari, M.D. 

“This is welcome news as progress has been very difficult against this cancer, and GOG physicians and patients who participated have made an important contribution,” said Jeff Abrams, M.D., clinical director of NCI’s Division of Cancer Treatment and Diagnosis.  Full data has been submitted to the American Society of Clinical Oncology 2013 Annual Meeting. The trial is GOG240, Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab for Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer, clinical trial registry number NCT00803062. 

NCATS Calls for Regulatory Partners to Develop, Market Potential Rare Disease Treatment  

The National Center for Advancing Translational Sciences (NCATS), the newest addition to the National Institute of Health (NIH), recently announced in the Federal Register that in combination with NIH’s National Human Genome Research Institute (NHGRI), it is seeking out a partner to, “collaborate in the final stages of lead optimization, evaluation and preclinical development”of two new therapies; one for Gaucher disease and the other for the treatment of heart failure and fibrosis, reported RAPS. 

According to the article in RAPS, NCATS believes that a novel selective series of non-inhibitory chaperones of glucocerebrosidase (GCase) will be useful in treating Gaucher disease and other related diseases.  “Gaucher is a rare disease affecting just a few thousand people in the US, and is most commonly found in those in Ashkenazi Jews, most of whom hail from Eastern and Central Europe.” 

The disease is marked by a lack of the GCase enzyme, which causes substances to build up in the body’s organs.  The severity of the disease depends on which of three types is inherited by the patient, but the disease is often fatal.  “NIH said it hopes its GCase chaperones will be able to guide the enzymes to lysomes after synthesis in the ribosome instead of accumulating in the endoplasmic reticulum.  This is more difficult than it seems, NIH wrote in its Federal Register announcement.” 

“The main challenge in the development of molecular chaperones for Gaucher disease is that chaperones are inhibitors of the enzyme. This complicates their clinical development, because it is difficult to generate an appropriate in vivo exposure at which a compound exhibits chaperone activity, but does not inhibit the enzyme’s function.” 

“The good news, it said, is that high throughput screening has identified several small-molecules that do not inhibit the enzyme.”  “These lead molecules were found to increase the specific activity of the enzyme, promote the translocation of GCase to the lysosome in Gaucher fibroblasts and macrophages, reduce the accumulated substrate, and restore efferocytosis of these cells.”  NIH added that the compound could also come to be used as a treatment for Parkinson’s disease, which exhibits some genetic parallels with Gaucher disease, or more generally to “enhance the efficacy of enzyme replacement therapy.” 

Then, NCATS referenced recombinant relaxin hormone, which NIH said is already in Phase III trials for the treatment of acute heart failure.  Researchers wrote that the compound is “difficult to study in chronic settings due to the short half-life and the need for intravenous administration of the recombinant hormone.”  A new, recombinant version of the hormone—the likes of which NCATS has been studying—would hypothetically “have numerous benefits and will allow investigating additional therapeutic applications where chronic administration is required.” 

“As with the GCase Chaperones, NCATS said it has successfully identified a series of small-molecule agonists that it said are ‘potent, highly selective, easy to synthesize, and with reasonable metabolic and physical properties’ that display ‘similar efficacy as the natural hormone in several functional assays.’” 

“If successfully marketed, the product could mean big money for its sponsor.  Heart failure—the disease which NCATS thinks this product would be most successful at treating—affects millions of Americans and is understood by the American Heart Journal to be the leading cause of hospitalizations for those over the age of 65.” 

RAPS noted that these announcements from NCATS were somewhat unusual because it was “looking for a partner that already has a sense of the regulatory challenges ahead of it.”  They noted that the Cooperative Research and Development Agreement (CRADA) “scope will also include studies beyond candidate selection including all aspects of pre-clinical studies such as toxicity studies and chemistry good manufacturing practice (GMP) scale up of select compound(s) and manufacture of controls leading to a successful investigational new drug (IND) application.”  

While NIH routinely licenses technology to outside groups, it does so “usually without the preconditions that it be able to bring a drug to market using the technology or their history as a company.” 

“Not so with its CRADA,” RAPS wrote.  “”Collaborators should have experience in the pre-clinical development of small molecules and a track record of successful submission of IND applications to the FDA for rare and neglected diseases,” NCATS added.  The agency said it hopes the compound can be “expeditiously commercialized and brought to practical use.” 

“Though the compounds are still relatively early in the development cycle—NIH notes that it’s only undergone early-stage in vivo and in vitro testing to determine absorption, distribution, metabolism and elimination (ADME) and activity studies on human macrophages—it still represents a potential new pipeline for patients suffering from rare or neglected diseases, as well as a potential source of profit for companies whose own pipelines have been notoriously stagnant in recent years.”