Advances in Drug Development for Multiple Sclerosis Pose Clinical Research Challenges

Considerable growth in multiple sclerosis (MS) research has led to more potential drugs in the development pipeline than ever before,¹ creating a double-edged sword for this therapeutic area. Although the recent uptick in MS clinical studies is likely to yield several new therapies for MS patients, it has also resulted in a diminished pool of available clinical trial patient candidates in the United States and Europe, a factor that impacts the speed of new drugs coming to the market.

“In many ways, pharmaceutical companies developing new drugs for MS have become victims of their own success, because the more robust the pipelines of new compounds, the more competition there is for clinical trial sites and subjects,” according to Maria Lopez-Bresnahan, M.D., M.B.A., Vice President and Global Head, Medical and Scientific Affairs, i3 Research.

“The industry recognizes that there is still an unmet need in the treatment of MS and so there are ongoing efforts to develop the most efficacious drugs with the best safety profile; there is an awareness that although there have been great strides over the last 15 years in therapeutic options, there is still no cure for MS,” Lopez-Bresnahan explained.

In addition to trials for new or improved parenteral treatments – currently the only approved type of drugs for MS – more trials are in progress for oral therapies, which are of particular interest to the MS community to eliminate the need for ongoing injections or infusions and their associated inconvenience and adverse effects, such as injection site reactions and discomfort.²

Further, a call for regulatory approval of generic versions – biosimilars or biogenerics – of innovator biopharmaceutical products following patent expiry, may increase the congested clinical research environment in MS because currently approved treatments are biologics. The European Medicines Agency (EMEA) already has regulatory pathway for biosimilars and have approvals in place for several biosimilar products, and there are two bills being considered in the U.S. Congress that would establish an abbreviated approval pathway for biogenerics provided that biosimilarity studies are conducted.³

“As biogenerics firms gain guidance from the Food and Dug Administration on developing MS biosimilars, there will be more demand for MS patients to enter clinical trials from an area where we have not had competition previously,” stated Lopez-Bresnahan.

Expanding MS trial site boundaries

With an abundance of clinical studies emerging to explore new drugs as potential treatment options, it has been increasingly more difficult for sponsors to reach MS trial enrollment targets quickly, especially in traditional study regions. Lopez-Bresnahan noted that “due to the large number of oral drugs and new infusion agents now under study, the competition for sites is very high and trials have become much harder to enroll rapidly.”

As a result, sponsor companies are turning to previously untapped regions, such as India and China, where the incidence of MS is lower, but the numbers of available study patients are high because the populations are so large. Clinical research organizations (CROs) can help sponsors make the move to emerging regions successfully, she said.

“When deciding where to conduct an MS study, sponsors need to know not only which countries and regions have sufficient patient populations to enroll in the trial, but also where there will be access to the sophisticated magnetic resonance imaging [MRI] scanners that are a requirement in MS research,” Lopez-Bresnahan said. “Finding a CRO with global expertise and experience in MS research goes a long way toward quickly identifying which site locations have the technology, manpower, medical expertise and patient populations that will lead to successful study execution.”

Also, because the regulatory requirements in different regions around the world are changing and are not synchronized, working with a seasoned CRO when making forays into new site locations can prevent trial complications and delays. With facilities in Dehli and Mumbai, i3 Research was one of the first CROs to conduct MS studies in India. “Our presence in the region allowed us to determine where in India the proper infrastructure existed to perform the trials, and to carefully execute and monitor them to ensure the highest quality data,” she said.

i3 Research clients also benefit from technology tools that leverage UnitedHealth Group data assets. i3’s CRAFT™ (Clinical Research, Analysis and Feasibility Tool) proprietary software allows i3 Research’s feasibility group to identify promising sites and potential investigators and search large databases for de-identified claims data about patients with specific diagnoses in order to facilitate subject recruitment.

Designing trials that yield quality results in a changing environment

Even when promising trial sites are found, in a highly competitive environment it is imperative that sponsors’ study protocols be designed very carefully, Lopez-Bresnahan advised. “To meet tight timelines and be first to market, sponsors simply cannot afford to run trials that are not designed and executed with the utmost efficiency,” she said.

Designing MS trials that meet appropriate clinical endpoints and regulatory requirements, and that are also appealing to potential subjects, is a key element of successful clinical protocols, she indicated. For example, because the parenteral drugs currently on the market are considered effective, an MS patient taking one of those drugs might be reluctant to enter a clinical trial where he or she might receive a placebo. “When competition for sites and patients is very high, the design of the trial becomes especially crucial,” she noted. “A significant number of patients are already on good treatments, so studies with an active comparator arm, instead of a placebo, tend to have an advantage in patient recruitment.”

Further, considering that the current standard of care for MS is parenteral therapy, i3 Research advises its clients designing trials for oral MS medications to include a patient education component. “For over a decade, patients have been treated with injectables and, more recently, infusion therapies, so there is a concern that they may be a little skeptical about the efficacy of a pill as compared to an injectable,” according to Lopez-Bresnahan. “Awareness of this type of issue and educating subjects on the importance of adherence to their study drug and compliance with the protocol will ensure the best trial results.”

Specialization adds value to clinical trial process

i3 Research’s goal of helping sponsors improve every aspect of their clinical trials is met by five therapeutically focused teams: oncology, cardiology, central nervous (CNS) system, respiratory and infectious diseases, and endocrinology and metabolic diseases. One of the subspecialties within the CNS area focuses specifically on MS research.

“i3 Research’s MS subspecialty team brings together neurologists and scientists with experience in all aspects of MS research who understand which type of protocol or plan is most likely to lead to drug approval,” Lopez-Bresnahan explained. “Because we have specific experience in this research area, we are much better equipped to look at a company’s clinical development plan and proposed protocols and provide the type of input that will help keep the program and studies on track and on schedule.”

And although i3 Research’s MS team is more similar to a smaller, “boutique” CRO, it has the resources of a larger infrastructure to give sponsors “the best of both worlds,” she said. For example, in addition to utilizing technology resources like CRAFT, the i3 Research team can include members from i3 Innovus, the health economics and outcomes research (HEOR) arm of the organization, to ensure that trials include the correct HEOR endpoints to yield data that  meets both regulator and payer requirements, and to help ensure successful product commercialization.

“This is critical in MS research,” commented Dr. Lopez-Bresnahan, “MS is a chronic disease that strikes young people at the moment when they are starting families and careers. Developing new drugs that can prevent them from having MS relapses, staying healthy, active and productive is the holy grail. i3’s team can make sure that we capture the correct quality of life and HEOR data that demonstrates those outcomes,” she said.

“Sponsors don’t have to find a separate company to handle the HEOR part of their drug development programs – it is all managed within one i3 team,” she said. “That synergy saves both time and money.” The combination of multi-functional teams with specific expertise allows i3 to understand the current status of clinical care, the competitive landscape of drug development in the field, and the practical aspects of running successful clinical trials around the world, Lopez-Bresnahan asserted.

“Having the right team in place with the right skill set makes an important difference in this field,” she said. “i3 Research’s therapeutically specialized approach, combined with our operational muscle and global footprint, offers sponsors a full-service experience that gives them a distinct advantage.”

¹ National Multiple Sclerosis Society Web Site (accessed June 17, 2009).
² Bernstein, Sara; “Research Highlights,” National MS Society (Summer/Fall 2007).
³ H.R. 1427, “Promoting Innovation and Access to Life-Saving Medicines Act”; and H.R. 1548, “Pathway for Biosimilars Act.”

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