Biosimilar Pathway Research Articles

US Biosimilar Pathway Unlikely to be Used†

In March 2010, the US passed the healthcare reform bill, including The Biologics Price Competition and Innovation Act of 2009, which established an abbreviated Biologic License Application (aBLA) pathway for the approval of biosimilars. The aBLA pathway may never be used. At the "Business of Biosimilars" meeting in Boston in September, developers of both innovator and generic biologics as well as representatives from the scientific, regulatory, and legal communities noted that, because of unclear requirements for clinical data and the need for public disclosure of proprietary data, manufacturers of generic biologics are unlikely to take advantage of the aBLA process, opting instead for a standard Biologic License Application (BLA). The implications of an unusable biosimilars pathway in the US dampen our already soft outlook for biosimilars. Companies will still develop follow-on biologics, but approved compounds will behave as new branded drugs. Biosimilars in the US are therefore not likely to lead to aggressive pricing, but will more likely mirror current situations where several similar biologics are available. For example, the interferon (IFN) β-1a products Avonex® and Rebif®, and Betaseron® (IFN β-1b) have all enjoyed >10% price increases for the last several years in spite of their clinical similarities. inThought reiterates its outlook for generic erosion of a typical biologic that projects a loss of revenue of 30% over 5 years compared to the 90% revenue loss for a typical branded small molecule.

The United States Food and Drugs Administration Approves a Generic Enoxaparin

The Food and Drug Administration (FDA) approved on July 23, 2010, the abbreviated new drug application (ANDA) by Sandoz Inc for a generic enoxaparin (Lovenox) as the FDA is satisfied with the active ingredient ''sameness'' and the interchangeability of Lovenox with this generic version. Regulatory authorities that consider low-molecular-weight heparins (LMWHs) as drugs approve generic LMWHs via an ANDA pathway, whereas EMEA views them as biological medicines and will therefore regulate copies of LMWHs via a biosimilar pathway because only similar copies can be manufactured. Furthermore, European Medicines Agency (EMEA) requires appropriately powered clinical trails to establish comparable efficacy and safety profiles for biosimilar and their branded LMWHs counterparts. The safety issues that have led to withdrawal of some generic LMWHs from some Asian and South American countries mandate the need for a broad consensus defining the minimum attributes copies of LMWHs required for efficacy and safety.

The therapeutic equivalence of complex drugs

When the patent of a small molecule drug expires generics may be introduced. They are considered therapeutically equivalent once pharmaceutical equivalence (i.e. identical active substances) and bioequivalence (i.e. comparable pharmacokinetics) have been established in a cross-over volunteer study. However this generic paradigm cannot be applied to complex drugs as biologics and a number of other therapeutic modalities. For copies of biologics the European Medicine Agency and other regulatory agencies have introduced a new regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. However for other complex drugs such as the iron–carbohydrate drugs, low molecular weight heparins (LMWHs), liposomal drugs and the glatiramoids regulatory guidance is still mostly lacking. In this paper we will discuss (therapeutic) experience obtained so far with these different classes of ‘complex drugs’ and their specifics to provide scientific arguments and criteria for consideration for a regulatory framework for the market authorization for these type of drugs.

Biosimilar Medicines—New Challenges for a New Class of Medicine

Biosimilars are a new class of medicine. The European Medicines Agency has pioneered the legal, regulatory, and scientific framework for approval of these products. One of the foundational principles of the European framework is that biosimilars are expected to be similar, not identical, to the innovator biologics they seek to copy. This contrasts with the legal, regulatory, and scientific framework for copies of chemical medicines, generics, which are based on the expectation that the innovator and generic drug substance are identical. This article reviews the European biosimilar regulatory pathway and reviews some of the clinical data being made public following the approval, rejection, and withdrawal of biosimilar marketing applications.

Developing a Legislative Pathway for Biosimilars in the United States

Biologies are one of the fastest growing, most important, and most expensive segments of the pharmaceutical industry. The high price of biologies in the United States is making these life-saving drugs unaffordable for many Americans and creating unsustainable burdens on purchasers. While the EU has created an abbreviated approval process for biosimilars, there is no explicit legislative pathway in the United States that would enable generic competition for biologics. The Promoting Innovation and Access to Life-Saving Medicine Act would provide such a generic pathway for biologics, using competition to lower drug prices. The bill provides an appropriate balance between access to affordable medicine and retaining incentives for innovation.

The Role of Recombinant Human Growth Hormone Biosimilars in the Management of Growth Disorders

Since ancient times plant and animal tissues have been used as medicines. In the 20th century growth hormone as a purified extraction from human pituitaries was still used to treat growth disorders. Since the genetic engineering of host cells became possible, a new generation of medicines obtained using recombinant DNA (rDNA) technology has emerged. These medicines have been named ‘biopharmaceuticals’. The first biopharmaceutical growth hormones were patented in the 1980s, so already over two decades of clinical experience support the development of a new, off-patent growth hormone preparation obtained by rDNA technology. The European Medicines Agency (EMEA) has put in place a centralised procedure for the approval of new biopharmaceuticals. This procedure includes testing comparability with a reference product and demands post-approval pharmacovigilance. Omnitrope® was the first off-patent recombinant human growth hormone (rhGH) approved on the basis of the biosimilar pathway; it underwent a very demanding approval procedure in 2006 and is now used for several indications in Europe, the US, Canada, Japan, Australia and other countries where it has received marketing approval.

Is Europe Ahead of the USA in Biosimilars?

This article is about a race between the USA and Europe in biosimilars. The race can be defined in several ways: the first launch of a biosimilar; the first cross-border use of a biosimilar in the USA or Europe which was approved in a neighbouring country; the greatest value or profits of biosimilars in 2004; the first legal provision for an abbreviated regulatory pathway applied in a consistent and continued manner; and the race for interchangeability or substitution of biosimilars for reimbursement, a race that is just beginning. The USA has won three of the five races, first-launch, first cross-border use and greatest value of biosimilars according to 2004 sales, but Europe is ahead in the most important race: the application of a consistent and continued regulatory pathway. This paper provides the race results and looks at the race for biosimilar regulatory pathways. Once the regulatory pathway is applied by governments in a consistent and continued manner and many biosimilars are launched, the race begins for interchangeability that affects physician prescribing and generic substitution. Biosimilar interchangeability and subsequent biopharmaceutical affordability, is the ultimate prize for the real winners of the race: the patients.