On Sakura Sogoro, Bottom-Up Social Movements, Biosimilars, and Access to Cancer Treatments

On Sakura Sogoro, Bottom-Up Social Movements, Biosimilars, and Access to Cancer Treatments

Gilberto Lopes, MD, FASCO, MBA

Oct 04, 2016

Sixty kilometers (40 miles) and a world away from Tokyo lies the city of Narita. Home to Japan's busiest airport and the gateway to its capital, this small town of 160,000 inhabitants is often overlooked—except for those of us schooled in the art of “onco-tourism.” I was introduced to that term by Daniel Haller, former Editor in Chief of the Journal of Clinical Oncology and current Editor in Chief of ASCO University. He described onco-tourism as flying to an airport, riding to the conference venue, and tracing our way back through those two without ever interacting with the people or seeing any of the sights in the host city or country.

That is all I thought I would have time do do when I arrived for a meeting to discuss biosimilars in East and Southeast Asia in early October 2016. Sometimes, however, the stars align and we can do more than that.

With half a day to kill and jet lag to ward off, I started running through a secondary street halfway between the airport and downtown. Soon, asphalt gave way to a narrow gravel road and tall bamboo, pine, and cedar trees, which flanked and covered the path, blocking my view of the sky. A mile down the road, the forest receded and green rice fields revealed themselves. Moving forward, a raised wooden platform took me through an orchard of persimmons, peaches, and mandarin oranges.

I continued through a nature trail. The falling rain painted the silky spiderwebs a silvery color that was visible dozens of meters down the path, allowing me to avoid disturbing their weavers (I would have no idea what to do for a Japanese spider bite, either). Dragonflies, birds I did not know, and a majestic crane flying by seemed to tell me I had wandered too far from the urban settings I'm more familiar with and that it was time to return. I obliged.

As I reached the sidewalk alongside the main highway, Japan's reputation as a thoughtful and detail-oriented host revealed itself. Every 10 meters (11 yards), tiles depicted maps and flags of countries from all over the world. The segment I passed through represented those in Africa and Australasia. A mile on, the tiles showed sacred sites: Buddhist temples, mosques, and ancient Hindu shrines from around the globe.

At the old village,  narrow houses (most are but 10 meters, or 30 feet, wide) with elaborate tiled roofs and painstakingly kept outdoor gardens dot the streets. In the smallest of homes, natural gas tanks and air-conditioning machines (lack of space is no excuse to forego modern comfort, even in classical settings) share their minuscule yards with the odd Mickey and Minnie Mouse sculpted in stone. A few open doors allowed me to catch a glimpse of the minimalist interiors with tatami-covered floors, bamboo screens, and teapots in central hearths. A wooden Shinto shrine and a 40x40-meter (44x44-yard) cemetery told me I was nearing the end of my run.

With the daylight almost gone I arrived at my destination: Naritasan Shinshoji Temple. I remembered the colorful three-story-tall, spiral-topped pagoda from my first visit to Asia a decade earlier, when a fortuitous delay on our way to Singapore allowed my wife and me to sleep near the airport and see this 1,000-year-old Buddhist temple for the first time. It felt appropriate that I should pay a visit and thank fortune for a blessed decade.

Although bad for taking pictures, the low light, especially with crickets chirping and ducks quacking in the background, made the complex seem even more serene and a good antidote for a 14-hour flight from Boston, where I had been lecturing on immuno-oncology for an audience of journalists from Latin America at the Harvard Faculty Club. Their main question? Where are we going to find US$100,000 or more per patient to be able to fund checkpoint inhibitors and newer therapies in places where the average family has to work nearly 20 years to make such an amount of money?

Biosimilars have the potential to plug that gap for medications with expired patents. While initial market expectations are that they might decrease costs by about 30%, recent experience with the biosimilar infliximab in Norway has been associated with an 80% markdown; it is likely that, in time, competition will bring prices down.

The abbreviated pathway most countries currently use for biosimilar approval is, nonetheless, more complex than the pathway for the approval of small-molecule generics, and it includes several types of studies that a company needs to submit for consideration. Analytical studies should demonstrate that the product is “highly similar” to the reference biologic agent, animal studies must show safety and efficacy, and clinical studies (including assessment of immunogenicity, pharmacokinetics, and pharmacodynamics) must prove the purity, safety, and efficacy of a biosimilar candidate.

Comparative phase III studies must be done in a sensitive, representative indication (usually, for cancer agents, with surrogate or intermediate outcomes rather than overall survival) and do not have to be repeated for other specific clinical indications once a drug is approved. These clinical trials, however, have significantly fewer patients than the studies conducted with the original reference biologic product. Post-approval research and vigilance on the safety and effectiveness of biosimilars compared with their innovator predecessors will clearly be needed to promote confidence in these new products. It should be self-evident, nonetheless, that follow-on biologics are here to stay. We truly hope that biosimilars will improve access to cancer medications in low- and middle-income settings.  

Our meeting in Narita, with representatives from not only Japan but also Hong Kong and Singapore, however, once more showed me that the oncology community is still very confused about several of these steps and will only be convinced of the appropriateness of using biosimilars after the full publication of early comparative studies and the availability of approved drugs. Much work is still to be done.

Feeling like I'm in an Akira Kurosawa movie as I again pass through winding roads and their timeless abodes and street-level shops on my way back to the hotel, the story of local folk hero Sakura Sogoro comes to mind. (For those in Boston or Cambridge, the Harvard Art Museum houses a series of woodblock prints telling his tale.) In the Tokugawa era, Kiuchi Sogo, as he is sometimes called, stood up to his feudal lord by pleading directly to the Shogun on behalf of his fellow farmers in an attempt to curtail their excessive taxes and work obligations. His punishment for this affront (you were not supposed to plead directly to princes, let alone to the big boss himself) was death. His abnegation and sacrifice have been sung in many progressive and reformist Japanese works of literature, and his tale has come to symbolize grassroots movements and their role in changing laws and rules. 

Around the world, patient groups, professional societies and other nongovernmental organizations have been working to increase access to cancer treatments. My colleagues and I recently published our experience in guaranteeing access to oral medications within the Brazilian supplemental health system.

Inequalities, especially in health care, breed discontent. We need better ways to continue incentivizing the development of new drugs while optimizing access. Biosimilars help, but they won't solve the whole problem. We need to continue supporting civil society groups aimed at improving access to cancer treatments around the world, and to look for more innovative ways to make it happen.


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