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Generic drugs have been an excellent value in our world of spiraling healthcare costs. Through price competition, they typically save the American consumer half the cost of the brand name or “innovator” prescription drugs for which they act as a substitute. 
For people with MS, whose annual drug costs can exceed $30,000, the opportunity for generic savings is helpful, if not critical, for maintaining health. But like most things having to do with MS, the pathway to these savings is...complicated.
Key MS drugs are technologically sophisticated—so much so that scientists, manufacturers, and regulators have for years been debating how to bring generic versions of these unique drugs to market. The generics envisioned have come to be called “biosimilars,” and as a result of healthcare reform, the groundwork for them to move forward has now been laid. Here are some basics on the past, present, and future of biosimilar drugs.
Q. What are biosimilars?
A. Biosimilars are to biologic drugs what generics are to traditional, chemically based drugs. Biologics are complex drugs made from living human or animal tissues rather than through usual chemical processes. They have changed the face of treatment for diseases including cancer, HIV/AIDS, and hormone deficiencies, as well as MS. The complexity of biologics means that they are difficult and expensive to make and can’t be exactly duplicated by different manufacturers—at least not to the degree that traditional drugs are duplicated as chemical generics. The term biosimilars or “follow-on drugs” has come to be used to differentiate biologic generics from traditional generics.
Q. What do biosimilars mean for DMT?
A. In disease-modifying therapy (DMT) for relapsing-remitting MS, the interferons Betaseron® (interferon β-1b), Avonex® (intramuscular interferon β-1a), and Rebif® (subcutaneous interferon β-1a) are biologics, as is the monoclonal antibody Tysabri® (natalizumab). Although Copaxone® (glatiramer acetate) is not manufactured from living sources, the molecules of this DMT are also intricate and large. As these innovator drugs begin to lose patent protection in the coming years, other manufacturers can attempt to copy and produce them and sell them at a lower cost. It does not mean that the innovator DMTs will change or stop being produced.
A new brand of interferon β-1b, Extavia®, has already been approved by the Food and Drug Administration (FDA) and is available. However, it is identical to Betaseron and produced by the same manufacturer, and is thus not technically a biosimilar. (The 2 drugs differ only in the needle size used for injection: 27-gauge for Extavia and a thinner, 30-gauge for Betaseron.) Betaseron itself remains available without change.
Q. What are the obstacles to approval of biosimilars?
A. For more than 25 years, the FDA has been approving generic drugs based on their measurable bioequivalence to innovator drugs. Proof of bioequivalence has given the agency the confidence to forego new clinical trials of the safety and effectiveness of generics before approving them. Equivalence between a biologic and a biosimilar is much harder to establish, given that biologics are based on living systems and created through delicate manipulation of large proteins, elaborate purification, and other sensitive processes. Indeed, experts concur that it’s virtually impossible to replicate a biologic using 2 different production systems. Thus the FDA has sought new authority and guidance from Congress for evaluating and approving biosimilars. (Note: Extavia was FDA approved without new clinical trials because it is the same product, made at the same site, as Betaseron.)
Q. What has changed to create a pathway to biosimilar drug approval?
A. Biosimilars have been a reality in the European Union since approval guidelines went into effect in 2005. By mid-2009, 13 bio-similars had been authorized there for disorders including anemia, growth hormone deficiency, and neutropenia (white blood-cell deficiency). Biosimilar guidelines are also in place in Switzerland, and preliminary drafts have been prepared in Canada and Japan.
Leading up to recent healthcare reform in the US, 2 bills relating to biosimilars were introduced in the House of Representatives, one by Rep. Henry Waxman and one by Rep. Anna Eshoo. The competing bills proposed different solutions to the following key questions about FDA approval of biosimilars:
Clinical trials—To confirm the safety and effectiveness of biosimilars, must they be compared to innovator drugs in clinical trials?
Interchangeability—Should a pharmacist be able to independently fill a brand-name prescription with a biosimilar (if there is no “do not substitute” order from the physician)?
Drug names—Must the brand-name and biosimilar drugs have different official names?
Exclusivity—For how long after their introduction should innovator biologics be protected from competition from biosimilars?
Debate on these bills culminated in the Biologics Price Competition and Innovations Act (or Biosimilars Act), which became a small part of the healthcare reform package enacted on March 23, 2010. The act stipulates that innovator biologics should have a 12-year period of exclusivity before a biosimilar can be considered for FDA approval. It requires that biosimilars have “no clinically meaningful differences” from innovator biologics in terms of safety, purity, and potency. Doctors should be able to prescribe them interchangeably. Importantly, the act requires that evidence of biosimilarity come from research that includes 1 or more clinical study.
Q. What can be expected on the pathway to biosimilars?
A. The FDA is now responsible for interpreting the new law and developing regulations and procedures for approval of biosimilars. Commissioner Margaret Hamburg, MD, has called for a “robust” and “science-driven” pathway that can still be customized on a case-by-case basis: “There will not be a one-size-fits-all approach.”
It is unclear how long the FDA will take to establish the framework for biosimilar approval. Important issues, such as the sharing or exclusivity of drug names, were not even mentioned in the Biosimilars Act. There may also be legal challenges with respect to patency and exclusivity provisions of the act. In the coming years, as biosimilar safety studies commence, people who take DMTs or other innovator biologics might encounter patient registries—similar to the registry now maintained for people taking Tysabri—that collect complete data on safety and effectiveness. These electronic databases will be an important source for comparisons with potential biosimilars, for which registries would also be created after FDA approval.
