Paying for CRISPR Cures: The Economics of Gene Therapies

By Alison Irvine | Innovative Genomics Institute (To be published December 2019)

Why does a pharmaceutical company charge $2 million for a life-saving treatment? Because they can.

On a sunny day at the Innovative Genomics Institute in Berkeley, California, experts gathered as part of The Berkeley Ethics and Regulation Group for Innovative Technologies (BERGIT) to explore solutions to the high cost of emerging gene therapies. New treatments offer the first signs of hope for treating many debilitating diseases. But these treatments are economically out of reach for most families.

Let’s imagine a scenario:

A mother brings her 15-month-old son to see their family physician. The boy has difficulty standing, falls often, and has failed to meet important milestones for a child his age. With the help of genetic testing, the physician diagnoses the child with Spinal Muscular Atrophy (SMA) — a debilitating genetic disease that causes weakness and atrophy in skeletal muscles, like those in the arms and legs, as the child ages.

Before 2016, there were no treatments for SMA. Two new genetic therapies offer hope for the first time. In 2019, Novartis announced the launch of Zolgensma, a one-time viral-based gene therapy designed to provide a fully functional copy of the faulty SMN1 gene that causes the disease.

But here’s the catch: Novartis has priced the gene therapy at $2 million per treatment.

An uninsured family would have to pay the entire cost themselves. But our patient’s family is lucky to have insurance. With their high deductible, they would have to pay $10,000 out of pocket up front for the new treatment. Even with family pitching in, they don’t have the payment in full and can’t afford the procedure to save their child’s life.

This struggle to cover medical expenses is currently the reality for many families in the United States.

How can a single therapy cost so much? It’s complicated.

 Getting a drug to market is a lengthy and expensive process. Clinical trials are the most costly phase. Even if the price to manufacture the drug is only a few cents, the cost of research, development, and clinical trials are built into the final price.

 Like any manufacturer, pharmaceutical companies try to price products at the so-called sweet spot, where profits are highest. But the price-point that yields the highest profits is always higher than the price point accessible to everyone. The problem is that pharmaceutical products are different from other products. When they are priced out of reach of those who need them, people suffer and die for the sake of profit.

 Research and development of small-molecule drugs is the most costly phase. Once the protocols and pathways are established, they should be relatively cheap to produce. This isn’t the case with gene and cell-based therapies.

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“Many of the manufacturers of these drugs like to advance the narrative that no one will be declined if they can’t afford it... This is a fantasy.” - Ross Wilson

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 Zolgensma, the newest treatment for SMA, is only approved for use in children under two years old. SMA is a relatively rare disease. Only 700 patients are eligible to receive the treatment. With expensive R&D costs and clinical trials, pharmaceutical companies still intend to recoup their losses. To compensate for the tiny customer base, the pharmaceutical company made the price sky high.

 With these numbers, it’s unsurprising that the US market funds the majority of the global pharmaceutical industry—roughly 80%. Prices for drugs are significantly higher in the US compared to other countries.

 James Robinson, Ph.D., MPH, is a Professor of Health Economics and Director of the Berkeley Center for Health Technology at The UC Berkeley School of Public Health. His focus is on innovation and affordability of medical technologies in the insurance, physician, and hospital sectors.

 “The only thing that drives down the price is competition,” Robinson explains. “Pharmaceutical R&D is mostly funded off of prices and profits in the industry, in turn, supported by the different patent and regulatory protections against the competition.”

 The US has an existing landscape for pricing traditional drugs — charge what the market will bear. But pricing for gene therapies is a new frontier: “The manufacturing and distribution [of traditional drugs] are very cheap… The marginal cost is zero. It’s not the same for gene and cell therapies,” says Robinson.

Developing a gene therapy can cost an estimated $5 billion. This is more than five times the average cost of developing traditional drugs. The therapeutics are subjected to multiple regulatory structures, which result in a long and expensive route to approval. When you factor in the limited number of eligible patients, the motivation behind pricing becomes clear.

According to a base-case analysis conducted by the Institute for Clinical and Economic Review (ICER), Zolgensma’s subjective value to their patients has been estimated to be around $900,000 per treatment. Still, nothing is stopping Novartis from inflating the price. Zolgensma’s only other competition is Spinraza, which, in comparison, requires a procedure every few months and can cost a total of $30 million over a lifetime.

Ross Wilson, Ph.D., is a Principal Investigator at the IGI. His lab works with enzymes such as Cas9 to test their efficiency for use in cell-based therapies. Wilson strongly believes it’s necessary to unpack the barriers to access patients will face: “Many of the manufacturers of these drugs like to advance the narrative that no one will be declined if they can’t afford it... This is a fantasy.”

The assumption is that insurers are going to cover the treatment no matter the price. However, we know this isn’t the case, and the high costs of treatment are not the only limiting factors for many families. Rena Conti, Ph.D., is the Associate Research Director of Biopharma & Public Policy for the Boston University Institute for Health System Innovation and Policy, as well as an Associate Professor at the Boston University Questrom School of Business. She is an expert on the demand, supply, and pricing of prescription drugs, particularly those used to treat cancer and other “specialty” conditions.

Conti emphasizes that even if the price of these drugs dropped significantly, patients still wouldn’t be able to afford these therapies: “This causes a lot of concern because even among the patients who are able to get the drug for free or low-cost… they still face very high affordability concerns related to the hospital bill, which don’t get written off as easily.”

So what can be done about access? There are a few options, but they all require an extensive overhaul in healthcare infrastructure. 

As an example, Louisiana's Secretary of Health, Dr. Rebekah Gee, recently entered into an agreement with Asegua, a pharmaceutical company, to provide life-saving drugs to treat patients with Hepatitis C. The condition is fatal if not treated, and the state estimated that 39,000 people in the Medicaid program and correctional facilities are infected. Yet, only 1,000 were treated in 2018. To Gee, this was unconscionable, so she negotiated an alternative approach.

The proposal was this: In exchange for a flat fee of $60 million, Asegua would be made the primary provider of Hepatitis C drugs for the state’s Medicaid and correctional populations. Over five years, Asegua would provide an unlimited supply of Hepatitis C treatment. The subscription service model gives healthcare workers the incentive to find and treat all eligible patients. The goal is to treat 31,000 patients during this timeframe. Each course of treatment is estimated to cost about $100 to produce.

This example shows that it is possible to make better practices in healthcare.. But it will take hard work, dedication, and new ideas on behalf of healthcare advocates. Conti explains the most likely scenario: “The state isn’t going to cover this. The burden of insuring access is fundamentally going to get played out in hand-to-hand combat with physicians in your city and mine.”

Regardless, Conti is an optimist. She believes that new cures need new financing mechanisms. “We can continue to prime the pump on research and development to make sure that pharmaceutical companies that bring new therapies to market face good economic incentives to do so. Part of that is related to the high prices they can charge, but it will also be due to the relaxation of regulations to defray the costs.”

Perhaps we can imagine a different scenario — one where our patient’s family isn’t turned away because of a high deductible or hospital expenses. Gene therapies have the potential to help millions of people. With fierce advocates in both the public and private sectors, change is possible. Let’s make sure these life-saving treatments are available to all who need them.

 To receive news about the next BERGIT meeting and take part in these crucial conversations, you can sign up for their mailing list. Participants can take part in person or via live stream.

To be published on www.innovativegenomics.org in December.

Egg Freezing Parties: A New Frontier in Reproductive Technology

The sounds of chattering and tinkling glasses echoed through the halls of the Crosby Hotel on a balmy Manhattan evening. It wasn’t an unusual sight for a night in SoHo, but this was no ordinary cocktail party.

At the front of the room stood Dr. Fahimeh Sasan, Practicing OB/GYN at Mount Sinai Hospital. Standing at the podium she opens with, "You may feel twenty, but your eggs sure aren't".

 These sobering words pierced through the auditorium filled with women of varying ages gathered at an "Egg Freezing Social". The event is hosted by Eggbanxx. They are selling a pause on the biological stopwatch.

Eggbanxx presents itself as an “affordable” egg-freezing solution for the working woman. Essentially, the company acts as a broker for egg retrieval.

Egg freezing has gained popularity in the past few years. Many egg banks market the service as a "back-up plan" for women who wish to preserve their fertility. With busy careers, women are waiting longer to have children due to demanding schedules or lack of stability. Celebrities like Kim Kardashian, Sofia Vergara, and Bridget Marquardt have made egg freezing a household topic. For Marquardt, it was an insurance policy: "It was a difficult thing for me to do, but I think that it was 100% worth it. I don't feel that clock ticking. I'm not worried about it." For many women, it relieves the pressure of starting families before they feel ready.

Over the past ten years, the fertility industry has grown into a multi-billion dollar business. Companies such as Facebook and Apple have begun to offer egg freezing as part of their employees' health benefits. Freezing your eggs suspends them in a sort of stasis. You keep aging, but your eggs don't. However, many women remain unsure of what the process entails.

As a woman in her twenties, I wanted to better understand all of my options. Embarking on the process of freezing my eggs for future use seems foreign and premature. Though according to Eggbanxx, you can never start too early.

Walking into the venue, a dull roar of constant chatter rose from somewhere in the hotel. At the entrance, a woman gave out pamphlets behind a folding table, claiming that Eggbanxx can offer 15% off treatments if I buy more than one cycle at a time.

 "Have you started working with a clinic?" asked a smiling representative from behind a stack of pamphlets. It was reminiscent of being offered a free cosmetic sample at a department store – they always expect you to buy.

On the evening of the cocktail party, reproductive endocrinologists, Dr. Janelle Luk from Neway Fertility, Dr. Serena Chen from IRMS Reproductive Medicine at Saint Barnabas, and Dr. Nicole Noyes, from NYU's Fertility Center, led an information session for the event attendees. Dr. Luk explained the freezing process, which includes quick freezing to avoid ice crystals, and boasted about her freeze-thaw success rate of 70-80%. The process is arduous. It requires hormone injections to prepare a woman's body to mature and release multiple eggs leading up to an invasive retrieval procedure. According to Dr. Serena Chen, women should ideally strive to retrieve 18-20 viable eggs to counter the 50% pregnancy rates.

The procedure can cost anywhere from $10,000 to $17,000 per cycle, which doesn’t include the $1000 annual storage fee. The number of eggs retrieved per cycle can vary, which often requiring multiple rounds of treatment. With an average cost of $13,500 per cycle, it’s out of grasp for many women of reproductive age.

Currently, there are many options for couples struggling with infertility. Common Assisted Reproductive Technologies (ART) include In vitro fertilization or surrogacy. In the process of trying to conceive, many couples opt for using either donor eggs or donor sperm. In the past decade, egg banks have become more prevalent in the US and abroad. To solicit egg donors, they often advertise to young women on college campuses with ads that read, "Make $6000 - $8000 on your summer break!" Many of these companies promise to pay more for donations from women with an Ivy League education or those that have an above-average IQ.

 The idea of egg donors is still a controversial one. Before 2009, New York state banned compensating women with state funding for egg procurement for research purposes. They feared coercion due to financial stress and questioned if women could consent under these circumstances. They have since authorized the payment of $10,000 per cycle.

Egg retrieval comes with its own set of risks. With the advent of trendy cocktail parties and flashy ads, companies like EggBanxx seem only to highlight their successes and provide very little information about possible risks or complications that could result from the retrieval process.

Only a few tell-all accounts of harrowing experiences with egg retrieval, whether for donation, compensation, or personal use, have surfaced in the past few years. The documentary "Eggsploitation" recounts stories of young women who underwent the process of egg retrieval for compensation, unaware of many of the risks involved. The hormone regime required to prepare a woman's body for the retrieval process can have adverse effects. They are at risk for ovarian hyperstimulation, torsioned ovary, or loss of reproductive health. There is also the risk that the hormones administered during the pre-retrieval phase can stimulate certain types of cancers to grow. With no prospective studies documenting the fertility status of young women freezing their eggs, the long-term health effects due to the egg freezing procedure are unknown.

EggBanxx representatives and fertility specialists relay medical information like salespeople trying to draw attention to the expert stitching on a designer bag – they are trying to make a sale. Plying us with themed cocktails and forced camaraderie had a clear purpose. Convincing women to undergo this process will lead to profit, but it also enters into a tricky ethical landscape.

Any reproductive broker, whether it’s an egg-freezing company or a surrogacy broker, already hints at the presence of exploitation. Ideally, their presence should ensure safety and oversight. But it can also make women, especially those in vulnerable populations, more susceptible to predatory practices.

Looking around the room, it was hard to not notice the sea of privilege. There is a real and unspoken danger that fertility service companies can exploit women in vulnerable positions to serve women in privileged positions.

It was easy to relate to both sides of this. I consider myself a woman of privilege. But not long ago, I was a student seized with financial anxieties. I would have felt tempted by almost any offer of $6,000 - $10,000. I still can’t afford the services offered by EggBanxx.

But none of us knows what the future holds.

And that may be the axis on which this whole business turns.

By Alison Irvine

Twitter: @alisonirvine1

Performing Science: Long Durational Discovery

By Alison Irvine

Colin Stringer films Noah Blumenson-Cook in the MEG Machine

 What can you learn from 6 hours in a neuroscience lab? Turns out, a lot. Imagine Science Films recently had the opportunity to accompany one of their new partners, Marina Abramovic Institute (MAI), to observe an NYU neuroscience lab. In the midst of a sea of lab equipment, both teams strove to immerse themselves in the scientific world.

MAI specializes in long durational performance. No less than six hours. From Abramovic’s perspective, both performer and audience need at least six hours to fully engage in the experience. Similarly, scientists know the draining effects of long duration all too well. From endless nights in the lab characterizing multiplying generations of bacteria, to days spent at the chalkboard reworking algorithms and formulas, time is recognized as the necessary factor for meaningful discovery.

© 2010, Laboratoria Art & Science Space. Suzanne Dikker places an EEG headset on Marina Abramovic for “Measuring the Magic of Mutual Gaze.”

This was not the first time that MAI teamed up with neuroscientists. Inspired by her long durational performance, “The Artist is Present,” which premiered at The Modern Museum of Art (MoMA) in 2010, Abramovic collaborated with neuroscientist, Suzanne Dikker, to create “Measuring the Magic of Mutual Gaze.” Curious about the neurological mechanisms underpinning Abramovic’s experience in “The Artist is Present,” Dikker designed an installation that, with the use of Electroencephalography (EEG) headsets, was able to visually record both participants’ brain waves to find moments of synchrony. Today, Imagine Science Films was able to visit Suzanne Dikker’s lab to learn more about their current research.

Colin Stringer from Imagine Science films Jess Rowland at work

Video of Imagine Science Films’ visit to Suzanne Dikker’s Lab.

The Performing Science column will explore the relationship between the performing arts and sciences, specifically concerning innovative methods to teach science through performance art. 

Alison Irvine is a theater artist and writer who recently graduated from Eugene Lang College with a degree in theater and interdisciplinary science.

Performing Science: The Science of Performance

 Performance art, often touted as theater’s elusive counterpart, is prone to attract abstract expressions of the human experience in all shapes and forms. With the image in our minds of performance artist Chris Burden crawling naked across broken glass, you may hesitantly ask how the medium of performance art can be applied as an effective learning tool in the sciences? In fact, you may be more than slightly hesitant.

There is a common misconception that the arts and sciences, though both require a great deal of skill and knowledge, cannot exist symbiotically in one practice. With recent initiatives to incorporate art as a useful tool in the STEM program in the U.S., new partnerships are emerging that, in spite of skepticism surrounding their compatibility, could prove to be the beginning of a lasting partnership that caters to a new type of learner.

The field of neuroscience pairs well with theater and performance art for it often asks some of the same questions: what is the impetus for human behavior? Why do we act a certain way under given circumstances, and then, in turn, act differently when put under the same circumstances? Unlike an experiment in a lab, you cannot repeat this test and expect the same results. In spite of these differences, parallels arise for both fields gain knowledge about the world based on information learned through observation or experimentation.

When asked about this dichotomy between science and art, astronaut and physicist, Mae Jemison, stated, “Differences between arts and sciences are not analytical versus intuitive. They are manifestations of the same thing… avatars of human creativity” (1). Though we prefer to make the distinction between analytical versus intuitive, right brain versus left brain, the separation cannot be made so easily. Recent initiatives have been undertaken by Marina Abramović Institute (MAI) in order to blur this line drawn between the arts and the sciences.

Breaching the Boundaries Between Arts and Sciences

Within the past few years, performance artist Marina Abramović has established herself as a force in the performance art world. In one of her most famous long durational works, “The Artist is Present,” which premiered at The Modern Museum of Art (MoMA) in 2010, served as part of a retrospective of her past work spanning over four decades. If you are not already familiar, the piece consisted of Abramović sitting in a chair seven hours a day for three months and inviting strangers to sit across from her in silence for any length of time to engage in mutual gaze. The responses of the participants were unexpected: some of them smiled, some of them looked uncomfortable, but most of them cried.

Marina Abramović in “The Artist is Present.” MoMA, 2010

How can the mere act of gazing into the eyes of another inspire such emotion? In an interview on NPR, Marina Abramović claimed that during her performance of “The Artist is Present,” one gentleman sat with her over twenty-one times (2). At the end of her performance, Abramović stated that she felt she knew this man “intimately,” and therefore, had no need to speak with him after the performance. Also being interviewed was neuroscientist, Christof Koch, who asked her what it was that she knew about this man? Could he set up an experiment where Abramović’s knowledge could be compared to the knowledge of a close friend? Koch’s discerning tone implied a level of doubt, but it’s not that he didn’t believe her; he simply didn’t understand her.

Abramović’s interest lies in the transfer of energy between performer and public. In an attempt to gain insight into the science of this feeling of connectedness, Abramović collaborated with neuroscientist, Suzanne Dikker and other artists on an artwork entitled “Measuring the Magic of Mutual Gaze” (3). In this piece, the concept and form was similar to Abramović’s original piece, “The Artist is Present,” but varied in that the experiment strove to gather tangible results by using a real-time index to measure brainwaves. Two participants sat across from one another fitted with electroencephalogram headsets (EEG) in order to measure brainwave activity. By engaging in mutual gaze, spectators could witness moments of synchrony in displayed images of these waves. Through the birth of these images, Abramović and Dikker accomplished a tall order: to make the invisible visible.

Suzanne Dikker and Marina Abramović in “Measuring the Magic of Mutual Gaze.” Garage Center for Contemporary Culture, 2011.

Not only are the images visually striking, but they also add validity to the phenomenon that Abramović described. It turns out, it is possible to achieve brainwave synchrony through gaze alone. Though the images serve as evidence for this connection, the experiment did not outline the specific areas of the brain that inspired this overwhelming feeling of emotion, nor do they explain Abramović’s claim of  knowing intimate details about others. The important question is, can Abramović’s experience be explained through complex neuronal activity or does this discovery beg for a deeper, more interdisciplinary approach to expose the mystery of the human brain?

Mirror Neurons: The Empathy Neuron?

Recently, mirror neurons have been advertised as what enables us to feel other people’s emotions. The importance of mirror neurons in human interaction has been a highly debated topic since their discovery in the 1990s by scientists at the Università di Parma in Italy. Activity in mirror neurons, also called “empathy neurons” found in the ventral premotor cortex (area F5) in Macaque monkeys, were shown to play a key role in a monkey’s ability to match their actions to the actions performed by another subject (4). The function of these mirror neurons work in direct correlation with something called gaze behavior. In this study, scientists recorded two sets of data: one for eye position and one for neuronal activity. They wanted to see whether or not looking at the presented action could influence mirror neuron visual response. Monkeys were asked to place their hand in a specific starting position, then after witnessing the scientist reach for a piece of food, they were asked to do the same. Scientists found that a higher portion of these mirror neurons were activated when the monkeys first watched this action be performed before they attempted to carry out the task.

A plethora of evidence from different scientific studies have either supported or debunked the claim that these mirror neurons allow us to gain insight into a deeper understanding of human behavior and experience. Neurons in the ventral premotor cortex were targeted as what allowed the monkeys to respond to the actions of another person. This data was then used to state that these neurons are what allow humans to understand the goals behind each other’s actions. Attempting to derive meaning from these studies, some neuroscientists even went as far to say that these neurons helped to shape our civilization. Though the importance of mirror neurons has been somewhat discredited over the past few years, the theory is still highly popular.

This in-depth study of mirror neurons may not be enough to state with certainty whether the premotor cortex is the area of the brain responsible for Abramović’s observation. Although, if this type of experiment can inspire scientists, artists, and the public to engage in scientific research, is a concrete explanation necessary?

Challenges Ahead

If you have ever tried to sit and gaze into someone else’s eyes for an extended period of time, I think we can all agree that it is uncomfortable. Being present and experiencing the moment is often described as an ability of a highly connected individual. However, this level of presence becomes increasingly harder to achieve as we move further into the technological age. We are comfortable interacting with gadgets, but with the onslaught of an increased Internet presence, I question how this impacts our ability to interact socially in a real world setting. Attempting to connect with another being demands vulnerability. Feeling exposed means taking a risk and during a session of intense mutual gaze, it becomes hard to hide.

According to Abramović, performance art is all about context: “If you bake some bread in a museum space it becomes art, but if you do it at home you’re a baker” (5). This too, could be applied to science. If art can be born through the juxtaposition of two opposing entities, maybe a change of scenery is enough to turn the task of streaking bacteria on to an agar plate into a performance piece. Despite future obstacles that will arise during the symbiotic working relationship between the performing art and the sciences, it cannot be denied that at their core, both artists and scientists share one vital ingredient: curiosity.

Imagine Science Films (ISF) is proud to announce a new partnership with the Marina Abramović Institute (MAI) to create a brand new science performance art series in order to explore innovative methods to engage the public in scientific issues.

Imagine Science Spotlight Film 17: Crowdsourcing Neuroscience with Suzanne Dikker.

By Alison Irvine @alisonirvine1

The Performing Science column will explore the relationship between the performing arts and sciences, specifically concerning innovative methods to teach science through performance art.

Alison Irvine is a theater artist and writer who recently graduated from Eugene Lang College with a degree in theater and interdisciplinary science.