IN SO MANY WORDS

Genentech’s Anne Fung, MD

In So Many Words is a succinct, timely talk with a need-to-heed KOL.

It’s been 10 years since the FDA approved Genentech’s Lucentis, aka ranibizumab, for wet AMD. With that decision, this South San Francisco firm became the first to offer patients an anti-VEGF therapy that could restore vision in many patients. “It’s true,” says Anne Fung, MD, Genentech’s head of Ophthalmology Medical Affairs. “Lucentis changed the retina game.” Today, that game has many potential players, most of which still seem humbled by this one hindrance: intravitreal administration.“Sustained delivery is a major challenge,” says Dr. Fung. “The fact that no one has developed something yet is proof of how difficult it is. It’s just one challenge we are facing at Genentech.”

Anne Fung, MD

Ophthalmology Management: When did you join Genentech?

Anne Fung, MD: In 2014. Our group identifies the most pressing clinical questions facing physicians and their patients. We partner with the [retina] community to discover these questions and use Genentech’s scientific resources to answer them. One question recently raised was whether DME patients who have poor vascular choroidal perfusion of the macula would do well with Lucentis. Retina specialists see fluorescein angiograms that look like hopeless cases and wonder if treatment would really help. We found that patients with macular nonperfusion, before being treated with Lucentis, had worse vision than the rest but after treatment they gained more vision and ended up with similar final vision as everyone else. It was surprising; it was more [of a gain] than the average patient.

OM: What is Genentech’s approach to therapy development?

AF: We look to understand and anticipate ophthalmology’s major unmet needs. For example, when we look at the preferences and trends surveys of ASRS and the CATT study five-year outcomes, we see that patients are not getting their therapies as often as they should to achieve their best visual outcomes. If you don’t give treatments frequently enough, they will slip.

OM: Tell us about LADDER.

AF: The Phase 2 LADDER study examines the sustained delivery of ranibizumab via a tiny device, the size of a grain of rice, that’s been implanted into the pars plana. We are looking at three ranibizumab formulations given via the sustained delivery device compared to monthly injections.

OM: Others are trying a sustained delivery system.

AF: There are many technical challenges in delivering a biologic over a long time period. From the beginning, we recognized that frequent injections were not the ideal way for drug delivery. This new device came out of a partnership with ForSight. Genentech has had many conversations, internally and externally, on how to deliver a biologic over a long period of time. Technical aspects of protein stability, concentration and viscosity continue to challenge scientists.

OM: You joined Genentech in 2014. How familiar were you with Lucentis?

AF: Actually, very. I did my fellowship at Bascom Palmer when Lucentis was completing its Phase 3 trial and one of the first investigator sponsored trials was starting. Phil Rosenfeld (MD, PhD) brought me on to help with PrONTO, which tested whether OCT-guided retreatment was doable.

OM: What was it like working with the Rosenfeld team?

AF: They taught me what it takes to do good research. I worked closely with the study coordinator team, Maria Esquiabro in particular, and she taught me the ropes of good clinical practice for research. I also got funding from Genentech for my own ISTs when I started in practice. They involved deeper studies of pigment epithelial detachment, a subtype of wet AMD. It was fascinating; I learned even more because I was in charge of the studies.

OM: So you continued with research after leaving Bascom Palmer?

AF: Yes. I came back to San Francisco, my hometown, and joined my dad’s practice and helped him grow the research program here. He is also a retina specialist.

OM: What standout lessons did you learn from your dad?

AF: My dad helped me understand that not only what you do in the moment, but what you leave behind, is important. He said it’s a way he can contribute in the long term. I have a deep appreciation for the concept of making a difference. I also learned about the relationship between physician and patient; I grew up with a real appreciation about this relationship over a lifetime. When I joined him in his practice, I inherited many of his patients. It is special to not only diagnose and take care of a disease, but to help a patient understand and cope with parts of the process. I value the personal touch of medicine.

OM: What is the status of the lampalizumab study?

AF: There are four studies, actually. Lampalizumab is a treatment for geographic atrophy, which has no approved treatment. Two trials are evaluating its safety and efficacy and two are evaluating the disease’s natural history and progression since little information exists. Measuring central visual acuity is common with trials, but here, we are looking at novel measures of functional vision, including reading speed and facial recognition tests. We hope to measure practical and functional vision that is most important to patients. These endpoints would be new to ophthalmology and the FDA.

OM: These must be easy endpoints to understand.

AF: Not quite. The FDA requires us to validate the new methods used for repeatability and reproducibility of the endpoints. The reading speed and facial recognition tests are brand new metrics. They are exploratory to see if we can validate these endpoints. Measuring the functionality of vision is important to our patients, which makes it important to us. OM

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