• Jackson Memorial Lecture: Avastin and OCT

    Today, some 70% of U.S. retina specialists use bevacizumab (Avastin) as an anti-VEGF agent. How did we get here? How did an oncology drug—used to treat colon, kidney, and other cancers—become a leading treatment for age-related macular degeneration (AMD)?

    That odyssey was outlined by Philip J. Rosenfeld, MD, PhD, in his Jackson Memorial Lecture, “The Lessons Learned From Avastin and OCT: The Great, the Good, the Bad, and the Ugly.” Dr. Rosenfeld was there from the beginning—he was the first to recognize Avastin’s ophthalmic potential and he led the drive to make it available as a safe, effective, and low-cost option for treating AMD.

    And as he made clear, the drug’s journey to acceptance has been full of plot twists and turns worthy of an Elmore Leonard novel, from patient-funded research to government audits, drug compounding, and even the unexpected death of a supportive colleague at a critical moment. Here are some highlights from Dr. Rosenfeld’s speech, which you can watch online (see below).

    A “perfect storm of events.” As Dr. Rosenfeld pointed out, Avastin’s eventual adoption by ophthalmologists would not have been possible without the advent of time-domain optical coherence tomography (OCT). This technology, introduced to the market in 2001, made it possible for researchers to document patients’ response to treatment.

    In a remarkable turn of events that he termed “a perfect storm,” the availability of OCT was followed by the approval of Avastin for metastatic colon cancer, as well as the approval of pegaptanib sodium (Macugen) for AMD, thus ushering in the era of intravitreal injections of anti-VEGF agents. At the same time, clinical trials of ranibizumab (Lucentis) for AMD were under way.

    Two drugs from one molecule. Initially, Dr. Rosenfeld investigated the systemic use of Avastin in AMD patients who had no other treatment option. However, concerns over systemic side effects sent him back to the drawing board.

    Before long, he realized that Avastin and Lucentis were essentially the same molecule, although Avastin was larger (ranibizumab is an antibody fragment of the parent molecule). “And now we’re off to the races,” Dr. Rosenfeld said—and, indeed, results from a series of clinical trials have supported his early findings that Avastin is safe and effective as a treatment for AMD.

    Bottom line. If you have 2 drugs that are equally safe and effective, how does the clinician choose between them? “Cost is what really drove Avastin’s use,” Dr. Rosenfeld said.

    Dr. Rosenfeld and his colleagues have continued to focus on the cost issue; in a recent study, they found that the use of Avastin from 2008 to 2015 saved Medicare $17.3 billion dollars.1 Medicare Advantage plans were not factored in to this analysis; if they had been, the overall savings would have risen to $24.7 billion dollars, Dr. Rosenfeld said.—Jean Shaw

    1 Rosenfeld PJ et al. Am J Ophthalmol. 2018;191:135-139.

    Watch online. Dr. Rosenfeld’s Jackson Memorial Lecture, along with the entire Opening Session, is available online via the Virtual Meeting. First sign in at aao.org/virtual-meeting (you will need your Academy login credentials), click “Sessions,” and then click “Archived Sessions” to find the Opening Session. You will be able to access archived sessions until Jan. 31, 2019.

    Financial disclosures. Acucela: C,S; Apellis: C,O; Astellas Institute for Regenerative Medicine: S; Boehringer-Ingelheim: C; Carl Zeiss Meditec: C,S; Chengdu Kanghong Biotech: C; DigiSight: O; Genentech: C,S; GlaxoSmithKline: S; Healios: C; Hemera Biosciences: C; Isarna Pharmaceuticals: C; Lin Bioscience: C; NGM Biopharmaceuticals: C; Ocudyne: C,O; Ocunexus: C; Tyrogenex: C,S; Unity Biotechnology: C.

    Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.

    Next story from AAO 2018—Meet the 2018 Laureate: Steven T. Charles, MD, an icon in the world of retina, is featured in a profile and video interview. He talks about his work and his work ethic.