Amgen 2015 Annual Report Download - page 33

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ongoing phase 3 study is evaluating the ability of Repatha® to prevent cardiovascular events, that study may fail to meet its clinical
efficacy endpoints or may identify safety issues with the product. (See We must conduct clinical trials in humans before we can
commercialize and sell any of our product candidates or existing products for new indications.) Even if the ongoing outcomes
study meets its clinical endpoints, regulators may not approve Repatha® for use beyond the currently approved label indications.
There may also be situations in which demonstrating the efficacy and safety of a product candidate may not be sufficient to gain
regulatory approval unless superiority to comparative products can be shown. The imposition of additional requirements or our
inability to meet them in a timely fashion or at all may delay our clinical development and regulatory filing efforts, delay or prevent
us from obtaining regulatory approval for new product candidates or new indications for existing products, or prevent us from
maintaining our current labels.
Some of our products have been approved by U.S. and foreign regulatory authorities on a conditional basis with full approval
conditioned upon fulfilling the requirements of regulators. For example, in December 2014, we received accelerated approval for
BLINCYTO® for the treatment of patients with Ph- relapsed or refractory B-cell precursor ALL in the United States, with continued
approval contingent upon clinical benefit in subsequent trials. BLINCYTO® also received conditional marketing authorization for
the treatment of patients with Ph- relapsed or refractory B-cell precursor ALL from the EC in November 2015. Regulatory authorities
are placing greater focus on monitoring products originally approved on an accelerated or conditional basis and on whether the
sponsors of such products have met the conditions of the accelerated or conditional approvals. If we are unable to fulfill the
requirements of regulators that were conditions of a product’s accelerated or conditional approval and/or if regulators re-evaluate
the data or risk-benefit profile of our product, our conditional approval may not result in full approval or may be revoked or not
renewed. Alternatively, we may be required to change the products’ labeled indications or even withdraw the products from the
market.
Safety problems or signals can arise as our products and product candidates are evaluated in clinical trials, including
investigator sponsored studies, or as our marketed products are used in clinical practice. We are required to continuously collect
and assess adverse events reported to us and to communicate to regulatory agencies these adverse events and safety signals regarding
our products. Regulatory agencies periodically perform inspections of our pharmacovigilance processes, including our adverse
event reporting. In 2012, pharmacovigilance legislation became effective in the EU that enhanced the authority of European
regulators to require companies to conduct additional post-approval clinical efficacy and safety studies and increased the
requirement on sponsor companies to analyze and evaluate the risk-benefit profiles of their products. Similarly, for our products
with approved REMS (see Item 1. Business—Government Regulation—Post-Approval Phase) we are required to submit periodic
assessment reports to the FDA to demonstrate that the goals of the REMS are being met. REMS and other risk management
programs are designed to ensure that a drug’s benefits outweigh the risks, and vary in the elements they contain. For example, our
ESA REMS requires applicable healthcare providers and institutions to enroll in the program, receive education about the product
and the REMS and document and report certain information to us over time. We are responsible for tracking and documenting
certain elements of healthcare provider and institution compliance with the ESA REMS, and we use third-party service providers
to assist in the administration of certain portions of our REMS. If the FDA is not satisfied with the results of the periodic assessment
reports we submit for any of our REMS, the FDA may also modify our REMS or take other regulatory actions, such as implementing
revised or restrictive labeling. If regulatory agencies determine that we or other parties (including our clinical trial investigators,
those operating our patient support programs or licensees of our products) have not complied with the applicable reporting or
other pharmacovigilance requirements, we may become subject to additional inspections, warning letters or other enforcement
actions, including monetary fines, marketing authorization withdrawal and other penalties. Our product candidates and marketed
products can also be affected by safety problems or signals occurring with respect to products that are similar to ours and that
implicate an entire class of products. Further, as a result of clinical trials, including sub-analyses or meta-analyses of earlier clinical
trials (a meta-analysis involves the use of various statistical methods to combine results from previous separate but related studies)
performed by us or others, concerns may arise about the sufficiency of the data or studies underlying a product’s approved label.
Such actual or perceived safety problems or concerns can lead to:
• revised or restrictive labeling for our products, or the potential for restrictive labeling that may result in our decision not
to commercialize a product candidate;
• requirement of risk management activities or other regulatory agency compliance actions related to the promotion and
sale of our products;
• mandated post-marketing commitments or pharmacovigilance programs for our approved products;
• product recalls of our approved products;
• revocation of approval for our products from the market completely, or within particular therapeutic areas or patient
types;
• increased timelines or delays in being approved by the FDA or other regulatory bodies; and/or
• fewer treatments or product candidates being approved by regulatory bodies.