Reflections on 2013-The First of the Breakthrough Therapies: A Payer Perspective

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As the FDA expedites approval of novel therapies, plans will need strategies to provide appropriate access while remaining observant of potential adverse events.

There were 27 new drugs approved by the US Food and Drug Administration (FDA) in 2013, down from the 16-year high of 39 drugs in the previous year.1 Among those 27 approvals, we also saw the first breakthrough drugs approved by the FDA. The breakthrough therapy designation is intended to expedite the development and review of drugs developed to treat serious or life-threatening conditions. This designation was created by the FDA Safety and Innovation Act (FDSIA), which became law in 2012. Section 902 of the Act provides for the new breakthrough designation, which is defined as a drug that is:

  • Intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition and
  • Preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant end points, such as substantial treatment effects observed early in clinical development.2

If a drug is designated as a breakthrough therapy, FDA is required to expedite the development and review of the drug by providing companies with extra meetings and earlier communication with FDA scientists. Breakthrough drugs should be differentiated from other forms of FDA accelerated programs. Those programs include:

  • Fast track: This status is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Designation may be granted on the basis of preclinical data. A sponsor of a drug that receives the fast track designation will typically have more frequent interactions with FDA during drug development. In addition, products that have been designated as fast track can submit portions of a marketing application before submitting the complete application, which is known as a “rolling review.”3
  • Accelerated approval: This program can be used for speeding the development and approval of promising therapies that treat a serious or life-threatening condition and provide meaningful therapeutic benefit over available therapies. Accelerated approval allows approval of a drug that demonstrates an effect on a “surrogate end point” that is reasonably likely to predict clinical benefit, or on a clinical end point that can be measured earlier than an effect on irreversible morbidity or mortality (IMM) that is reasonably likely to predict an effect on IMM or other clinical benefit.3

While the fast track and breakthrough therapy designations are similar, there are subtle differences. A breakthrough therapy program is for a drug that treats a serious or life-threatening condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant end point(s) over available therapies. In contrast, a fast track program is for a drug that treats a serious or life-threatening condition, and nonclinical or clinical data demonstrate the potential to address an unmet medical need.2 In January of 2013, Vertex disclosed that 2 of its cystic fibrosis therapies were granted breakthrough therapy designation status by the FDA. And later that same year, 3 therapies that were granted breakthrough therapy designation status by the FDA received approval. The first of those breakthrough drugs was Gazyva (obintuzumab)(Genentech), approved in October 2013 for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).3 Gazvya is a humanized anti-CD20 monoclonal antibody of the immunoglobulin G, subclass 1 (IgG1) that recognizes a specific epitope of the CD20 molecule found on B cells.

The second breakthrough drug, Imbruvica (ibrutinib)(Pharmacyclics, Johnson & Johnson), was approved in November 2013 as a treatment for mantle cell lymphoma. This agent inhibits the function of Bruton's tyrosine kinase (BTK). BTK is a key signaling molecule of the B-cell receptor signaling complex that plays an important role in the survival of malignant B cells. Of note is that the FDA subsequently approved Imbruvica for the treatment of CLL in early 2014.4

The third breakthrough drug approved in 2013, in December, was Sovaldi (sofosbuvir)(Gilead). Sovaldi oral tablets are used as part of a regimen for the treatment of chronic hepatitis C virus (HCV) infection caused by genotypes 1, 2, 3, or 4. According to the FDA, Sovaldi is the first drug that can be used without an interferon product to treat certain types of chronic HCV infection.5

All of these drugs represent significant therapeutic advances in their respective fields. However, they come at substantial premium prices. Therefore, plans are cautiously managing access to these new agents. While they have the potential to provide significantly improved clinical outcomes, the limited experience with these drugs in the clinical development stage raises concerns about the potential for the emergence of previously unknown adverse consequences. Therefore, it is likely that plans will continue to monitor clinical outcomes with these agents closely and restrict usage to the FDA-approved indications until wider clinical experience is gained and data emerges on potential additional uses. With the likelihood that more therapies will be approved through these various expedited processes, plans will need to continue to evolve strategies to provide appropriate access to these new agents while remaining observant to the potential for untoward consequences.


  1. FDA new drug approvals hit 16-year high in 2012. Reuters. Published December 31, 2012. Accessed March 5, 2014.
  2. US Food and Drug Administration. Fact sheet: breakthrough therapies. Updated August 21, 2013. Accessed March 2, 2014.
  3. US Food and Drug Administration. Frequently asked questions: breakthrough therapies. Updated March 3, 2014. Accessed March 3, 2014.
  4. Gazyva (obinutuzumab). Center Watch website. Accessed February 27, 2014.
  5. J&J pharmacyclics win early approval for ‘breakthrough’ cancer drug ibrutinib. Fierce Biotech website. Published November 13, 2013. Accessed February 27, 2014.
  6. American Society of Health System Pharmacists; Sofosbuvir approved for Hepatitis C Infection; Accessed February 23, 2014.