Huntington’s disease community will 'get there' in search for therapies, CHDI chief scientist declares after ‘terrific’ conference

 

After presiding over a “terrific” research conference, CHDI Foundation Chief Scientific Officer Robert Pacifici, Ph.D., declared that the Huntington’s disease community will “get there” in the search for long-awaited therapies.

 

Dr. Pacifici commented in an interview with me on March 1, after the CHDI-sponsored 19th Annual HD Therapeutics Conference, held in Palm Springs, CA, from February 26-29.

 

The CHDI chief scientific officer (CSO) provided his optimistic assessment in referencing the featured presentation by David Altshuler, M.D., Ph.D., CSO of the Boston-based Vertex Pharmaceuticals.

 

“They’ve solved some unbelievably difficult problems,” Dr. Pacifici said of Vertex, noting that it found a cure for hepatitis C.

 

Vertex has also developed therapies for three tough diseases that, like HD, are genetic: cystic fibrosis, sickle cell disease, and transfusion-dependent beta thalassemia.

 

At future therapeutics conferences, “we would love for the last talk” to focus on a new drug that is “now going to be approved,’” Dr. Pacifici told me.

 

“We’re going to get there,” he continued. Dr. Altshuler, who Dr. Pacifici said carefully calibrates his optimism, “was very complimentary and very confident that if we stay on this path, we’ll actually achieve that. He felt that the collective efforts that CHDI is trying to catalyze throughout the community are going to be successful.”

 

Dr. Pacifici pointed out how CHDI has adhered to another key principle of drug discovery emphasized by Dr. Althsuler: studying HD in human cells, tissues, and postmortem samples.

 

Dr. Pacifici said he expects the HD field will hear more from Dr. Altshuler and welcomed Vertex’s possible revived involvement.

 

In 2010 I spoke on my family’s fight against HD at the Vertex labs in San Diego and chronicled its search at the time for an HD therapy, though so far without results reported by that lab.

 

Dr. David Altshuler presenting a timeline of Huntington's disease scientific landmarks at the 19th Annual Therapeutics Conference, February 28, 2024. Pictured in the slide is James Gusella, Ph.D., whose lab discovered the huntingtin genetic marker in 1983 and the gene in 1993 (photo by Gene Veritas, aka Kenneth P. Serbin, and posted with permission of CHDI Foundation). (Click on the image to make it larger.)

 

The need to celebrate milestones

 

“But I think what you will see is incremental successes,” Dr. Pacifici continued. “We’re going to have these new findings, these critical milestones and stepping stones along the way that we should embrace and celebrate and use those as a source of hope that, even though it never moves as fast as we would like, we’re making very real, tangible progress”

 

Dr. Pacifici described the 19th conference as “terrific,” noting that more than 450 people – a record – 50 companies, and 70 academic institutions took part. He recalled how no biopharma firms attended the first few conferences. Now such companies “come to a conference because they think an area is ripe for discovery,” he observed.

 

“Everybody commented on how quickly the conference went this year,” Dr. Pacifici said. “There was just so much information and so much happening and actually people were sad when it was over.”

 

I found this, my twelfth CHDI conference, particularly exhilarating because of the amount of new data and the high quality of the presentations.

 

A virtual nonprofit biotech, CHDI is the largest private funder of HD research. As in our interviews at past therapeutics conferences, Dr. Pacifici summarized the key findings of the scientists’ presentations. Watch our 39-minute interview in the video below.

 

 

Key developments

 

Dr. Pacifici explained several key developments.

 

The session on new data and insights into the basic biology of HD included presentations that help “to understand exactly how we can custom craft the profile of candidate drugs to make sure that they hit the right things and are as safe as possible,” Dr. Pacifici said. Such crafting would mean that drugs could effectively address the numerous specific problems in HD, he added.

 

Another session “shined a bright light” on DNA repair, modifier genes, and somatic instability, the tendency of the deleterious expansion of the DNA to worsen with age and therefore trigger disease onset, Dr. Pacifici said. The new findings can contribute to the ongoing effort to “manipulate” these processes to slow or stop instability and therefore prevent the disease, he explained.

 

Including talks detailing HD at the cellular and molecular level, the session titled “It’s a Brain Disease” was “unbelievably informative” about specifying how HD harms the brain, Dr. Pacifici said.

 

Clinical trial news and the importance of participation in research

 

The final session featured clinical trial updates from uniQure, PTC Therapeutics, and Roche. None of these has yet reached Phase 3, the definitive test of a drug.

 

Referring to the 2021 results of Roche’s first attempt at a Phase 3 trial, Dr. Pacifici noted that the firm’s scientists “have really gone to town and reanalyzed the samples, reanalyzed the data in a way that is hopefully going to teach us not only why that particular trial didn’t meet its endpoints” but also “what we can do differently.” Roche’s reassessment of its drug, tominersen, in a Phase 2 trial, GENERATION HD2, is in progress.

 

Ultimately, the field needs a “conveyor belt” of new drug possibilities to develop the multiple kinds of drugs necessary for treating different aspects of HD, Dr. Pacifici concluded. Not all those new drugs will be successful, he said, but the more produced, the greater likelihood for successful therapies.

 

Dr. Pacifici pointed out that many of the discoveries discussed at the meeting resulted from the human data collected from tens of thousands of research volunteers.

 

Future projects and breakthroughs will continue to rely on large numbers of participants, he said. Some individuals may carry unique genetic characteristics revealing new kinds of therapies.

 

“Hang in there,” Dr. Pacifici said in his closing comment for the HD community. “I hope that next year at the 20th [conference] we’ll have some more good news to communicate.”

 

Stay tuned for further news from the conference!

Can we afford the costs of orphan disease treatments?

Millions of people in America suffer from rare, or “orphan,” diseases, conditions defined by the government as affecting fewer than 200,000 people. With an estimated 30,000 affected individuals, Huntington’s disease is one of the more common of these disorders.

The pharmaceutical industry has largely ignored these diseases, which number several thousand, because each disease promises too few customers/patients to enable companies to recoup investments in drug research and development and therefore generate a profit. The market usually doesn’t work for people with these diseases.

News about a lawsuit by Arkansas cystic fibrosis (CF) patients against the state’s Medicaid program for its refusal to pay for a highly effective but extremely expensive drug – Vertex Pharmaceutical’s Kalydeco – shined light on this predicament.

In an article titled “The $300,000 Drug,” New York Times columnist Joe Nocera recognized Kalydeco as a “wonder drug” but questioned whether the country can afford the personalized medicine approach that enables scientists to design specialized treatments for very small and specific groups of patients.

With an annual wholesale cost of $311,000, Kalydeco was developed for a subgroup of about 1,100 CF patients with specific genetic mutations. The subgroup numbers about 2,150 patients worldwide in an overall CF population of 70,000 individuals.

“Because patients will likely be taking the drug for the rest of their lives, it could cost millions of dollars to keep just one patient on Kalydeco,” Nocera speculated. “That raises another important question about the coming of personalized medicine. How are we, as a society, going to pay for it?”

Same question for the HD community

The HD community could face this very same question. Because the U.S. has only 30,000 HD patients and 150,000 to 250,000 people at risk of carrying the gene, a potential treatment could cost a lot.

Boston-headquartered Vertex has sought to develop HD treatments since mid-2008. Though the company has made a substantial effort, it doesn’t yet have plans for a clinical trial. (Click here to read more.) Isis Pharmaceuticals, Inc., of Carlsbad, CA, has also worked about as long and is planning to launch a clinical trial in the next year or two.

It’s still too early to project the costs of treatments that have yet to be tested or even fully designed. Other potential remedies are in trials but at best likely remain years from reaching the market.

Furthermore, an HD treatment regimen will likely involve a cocktail of remedies, meaning that patients – via their insurers – will probably have to pay for more than one drug.

Vertex vice president of research Paul Negulescu (left), Gene Veritas (aka Kenneth P. Serbin), and Vertex vice president of biology Beth Hoffman at the company's San Diego facility, September 2010 (photo by Heather Farr, Vertex)

Patient assistance programs

The HD community must remain vigilant regarding the cost of potential treatments. However, failing to consider a number of factors, the coverage of the Kalydeco costs was perhaps too pessimistic about the future.

First, as I commented regarding the impatience with California’s stem cell institute after ten years of operation without a drug, biomedical research is slow by nature. And it’s expensive, with the average cost of developing a new drug in the U.S. at $1.2 billion. Only one in ten clinical trials results in a marketable drug, although the research from the unsuccessful projects provides highly valuable information on what does not work.

In the case of CF, Vertex is at work on another treatment that would reach thousands more patients with different kinds of mutations.

As Nocera himself noted, Vertex provides Kalydeco for free to patients without insurance.

Lundbeck, the pharmaceutical firm that markets Xenazine, which diminishes some of the involuntary movements caused by HD (chorea), provides financial assistance to patients who qualify. Depending on the dosage, the annual wholesale cost of this treatment can reach $50,000 or more, but, according to the Lundbeck website, “85 percent of U.S. patients taking Xenazine have a monthly co-pay of $50 or less before requesting co-pay assistance.”

It’s highly conceivable that the developers of future HD treatments will provide similar kinds of assistance – especially because these firms will have relied on the good will and extensive cooperation of HD families who participate in research studies and clinical trials. However, it’s not clear what the drug companies will charge insurers.

CHDI and pharma giants

After the founding in 2003 of the CHDI Foundation, Inc., a non-profit virtual biotech firm backed by wealthy donors who wish to remain anonymous, pharmaceutical firms small and large started to gain interest in developing Huntington’s treatments.

As a result, the network of firms working on HD now includes pharmaceutical giants such as Pfizer, Roche, and Medtronic.

As a non-profit with the sole purpose of finding HD treatments, CHDI promotes research on Huntington’s and the diffusion of scientific knowledge about the disease. With more researchers and firms involved, the chances for treatments have grown. Having more options could very well mean that treatments would cost less.

By pouring hundreds of millions of dollars into HD drug research, CHDI has created an incentive to produce cheaper drugs.

As it states on its website, CHDI seeks to connect academic research, drug discovery, and clinical development in order to avoid “costly delays to therapeutic development” and make potential treatments a “good investment” that will result in “full clinical development, including licensure and marketing to get drugs to HD patients.”

Similarly, the Hereditary Disease Foundation and the Huntington’s Disease Society of America (HDSA) have supported research that could yield yet additional drugs.

Patient-driven medicine

Thanks to this level of support for HD research, the HD community stands in perhaps a better position than those facing even more rare diseases.

Nevertheless, orphan disease communities in general have reason to feel optimistic about both the development of treatments and their cost, if the vision of one key medical leader becomes reality.

Lee Hood, M.D., Ph.D., one of the scientific giants behind the Genome Project and the recipient in 1987 of the Lasker Basic Medical Research Award (the American equivalent of the Nobel Prize), has developed a plan for more effective and affordable medicine. In 2000, Dr. Hood founded the Institute for Systems Biology (ISB). Located in Seattle, the non-profit ISB teams scientists and technologists from many disciplines to pioneer the future of research in biology, biotechnology, medicine, environmental science, and science education.

In a 2012 speech at the Seventh Annual HD Therapeutics Conference, sponsored by CHDI, Dr. Hood outlined the importance of systems biology – what I think of as the “big picture” of disease – for HD research. Dr. Hood also advocated for the adoption of P4 medicine: predictive, preventive, personalized, and participatory. (Click here to read more.)

“Patients and consumers will be a major driver in the realization of P4 medicine through their participation in medically oriented social networks directed at improving their own healthcare,” Dr. Hood and Mauricio Flores, J.D., wrote in the March 2012 issue of the journal New Biotechnology.

ISB and several collaborating organizations have run some pilot programs in P4. If it is implemented on a wide scale, Dr. Hood predicts that it will revolutionize our healthcare system. Everybody will carry a health-monitoring device, and diseases will be predicted and prevented long before onset as the result of tiny blood samples taken from a pin prick, the article states.

Predicting falling medical costs

Significantly, costs could plummet.

“P4 medicine will require that all healthcare companies rewrite their business plans in the next 10 years or so,” Dr. Hood and Flores wrote. “Many will not be able to do so and will become ‘industrial dinosaurs.’ There will be enormous economic opportunities for the emergence of new companies tailored to the needs and opportunities of P4 medicine.”

The authors projected that savings will result from a series of factors, including earlier and more effective diagnosis of disease; better matching of drugs with diseases and their subtypes; better identification of genetically based adverse reactions to drugs; the ability to “re-engineer” disease-affected biological networks within people in order to reduce the cost of drug development; an increasing ability to deal effectively with cancer; the use of stem cells for replacement therapy and diagnostics; the routine extension of effective mental and physical health into people’s 80s and 90s; an improved understanding of microbes in the body; a deeper understanding of neurodegeneration (the cause of HD, Alzheimer’s, Parkinson’s, and other disorders); and the digitalization of medical and genetic information.

“On another tact, our prediction is that there will be a ‘wellness industry’ that will emerge over the next 10-15 years that will in time far exceed the size of the healthcare industry,” Dr. Hood and Flores affirmed. “P4 medicine is an area replete with economic opportunities.”

Dr. Hood and Flores believe that P4 medicine will “democratize” healthcare.

“The patient (consumer), through social networks, will drive the emergence of P4 medicine,” they wrote. “Because of intrinsic conservatism and sclerotic bureaucratic systems, physicians, healthcare specialists and the healthcare industry will take a back seat to the power of patient-driven social networks in bringing change to the healthcare system. Indeed, patients may be the only driving force capable of truly changing our contemporary healthcare system to the proactive P4 mode.”

This scenario serves as a serious alternative to the dim view that orphan disease communities will remain relegated to high-cost solutions.

Guaranteeing proper care standards

Indeed, a “revolution” has occurred over the past two decades in how patients have related to their doctors and the pharmaceutical industry (click here to read more).

Nowadays, people enter the healthcare system as both patients and advocates for their well-being.

This outlook led the Arkansas patients to sue for the right to have their Kalydeco costs covered.

Their lawsuit offers a striking similarity with the HD community’s pressure on the Social Security Administration and Congress to update the decades-old, inaccurate government criteria for determining disability benefits for Huntington’s patients (click here to read more). The Arkansas plaintiffs in effect have demanded that the state recognize Kalydeco as the standard treatment for their type of CF.

Negotiating the price

The competition of the marketplace, greater efficiency in drug development, and the revolution in medicine outlined by Dr. Hood should put downward pressure on the cost of drugs.

Patient advocates must play a crucial role in this process.

As the late San Diego biotech leader Duane Roth had told me during a dinner with California stem cell leaders in 2008, patient advocates must find ways to appeal to pharmaceutical companies’ primary interest in profits. Advocates need to lobby and court these business leaders.

At the same time, disease organizations such as HDSA and its network of advocates can pressure pharmaceutical companies and government agencies to assure new drugs’ accessibility and affordability.

In some circumstances, government can join in the process of persuasion and even play hardball, as the Brazilian Ministry of Health did in the 1990s in order to convince multinational pharmaceutical firms to dramatically reduce the price of HIV/AIDS medications. The Brazilian government provides HIV/AIDS drugs for free.

“Local production of generics, the possibility of breaking patents, and the offer of technology transfer became instruments for price negotiations with other countries and the pharmaceutical industry, leading to a real reduction in prices on the Brazilian and international markets,” wrote the coordinator of the country’s National STD/AIDS Program.

The marketplace exists, but it is susceptible to politics.

The rhetoric about the $300,000 drug can scare a lot of people. But in the long run, such a cost is not a foregone conclusion.

Feeling the hope

(I dedicate this article to the dozens of people who joined or supported the “Serbin Family Team” on April 14 in the 2013 Team Hope Walk-San Diego of the Huntington’s Disease Society of America, HDSA.)

Lately, I’ve been feeling great hope – even as my genetic clock ticks ominously – that researchers will find an effective treatment for Huntington’s disease and save me from following in the footsteps of my mother, who struggled against this so-called “devil of all diseases” for nearly 20 years before succumbing at age 68 in 2006.

Because the underlying causes of HD are untreatable, I’ve rarely permitted myself to have all-out hope during my 15 years of advocacy and personal fight to avoid the inevitable symptoms. I’ve braced myself for the impact of onset, even as I keep advocating for the cause on full throttle until our community, together with the scientists working overtime for effective treatments, achieves victory.

Hope is a precious commodity to be savored when breakthroughs occur. I’ve saved a couple bottles of Hangtime Pinot Noir, the wine served at the Parker Palm Springs hotel in 2011 at a reception after my first major speech on HD, delivered at the Sixth Annual HD Therapeutics Conference, sponsored by the CHDI Foundation, Inc., in February 2011. I’m keeping at least one to celebrate on the day a treatment is announced.

Big news, a sense of relief – tempered by reality

In recent weeks, the science news and advocacy milestones have left me feeling particularly buoyant.

On April 2, I was thrilled with President Barack Obama’s announcement of the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative, which will spend hundreds of millions of dollars over the next decade to map the mysterious circuitry of the brain. Although HD researchers hope to find treatments before the potential benefits of BRAIN become available in a decade or more, the announcement of the project finally brings brain health and research to a long-overdue prominence in American politics.

The very next day, HDSA held a symposium at the U.S. Senate to mark the 20^th anniversary of the discovery of the HD gene. Dr. Francis Collins, the director of the National Institutes of Health and one of the scientists who helped find the gene, keynoted the meeting, which included presentations by key HD researchers about the prospects for treatments. As I watched the live streaming video of the event, I could feel the sweep of history as I reflected on the scientists’ words and my family’s odyssey with HD, beginning with my mother’s genetic test in 1995 and my own test in 1999.

Just a few days later, on April 8, the Swiss pharmaceutical giant Roche and Carlsbad, CA-based Isis Pharmaceuticals, Inc., announced a multi-million-dollar partnership to bring Isis’s potentially revolutionary HD gene-therapy drug into clinical trials, with a projected start date of the first half of 2014. I have followed the Isis project closely since 2008, visiting the company’s labs, interviewing its scientists, writing detailed articles about the research, and, in speeches to the HD community, citing the project as a great sign of hope.

As I prepared an article on this latest phase of the project, I felt a profound sense of comfort and elation as I pondered how the deal with Roche should accelerate the research, increase the potential for effective results for symptomatic HD people, and, for the very first time, allow scientists to envision ways of preventing presymptomatic people like me from ever developing the disease!

I let out a long sigh of relief – as I do again now in writing these words – and imagined a future without HD for me and the tens of thousands of families around the world devastated by the disorder.

However, since then I’ve tempered my enthusiasm with reality. Although scientists express genuine optimism about developing treatments, only one in ten clinical trials leads to a drug.

As I race against my genetic clock and past my mother’s age of onset, a treatment may not arrive in time to prevent my symptoms.

Nevertheless, the great feeling of hope lingers and brightens my days!

Our generous supporters

In the midst of these events, my wife, my daughter, and I sought fundraisers and walkers for the April 14 Team Hope Walk.

In the wake of my definitive exit from the “HD closet” (in an article in The Chronicle of Higher Education and an interview on the website of my employer, the University of San Diego), nearly 70  friends, colleagues, and other supporters donated more than $16,000 to the “Serbin Family Team” – more than three times our goal. (Overall, local HDSA board members expected the event to net more than $40,000 for the organization.)

Twelve volunteers joined us in the 5K walk at Tidewater Park in Coronado, CA, to help raise awareness about HD.

Members of "Serbin Family Team" at 2013 Hope Walk-San Diego (photo by Vince Margetta)

I felt enormous pride in my family, my friends and supporters, and the HD cause.

Love and humility

I was moved most by donations from individuals and families themselves hit with serious illnesses, all of them with at least a partial genetic basis: breast cancer, colon cancer, young onset Parkinson’s disease, fragile X syndrome, and multiple sclerosis.

My family and I learned of these other families’ struggles, including, in one case, a harrowing decision about genetic testing.

I was deeply moved by this outpouring of generosity and love.

For me, it was also a lesson in humility, a reminder that so many others suffer from disease, an opportunity to become more sensitive to others’ needs, including the need to support other causes.

Above all, the immense display of support for the “Serbin Family Team” stirred in me the same feeling of hope that I experienced in contemplating the Roche-Isis project.

Hope wins out

Sadly, just two days before the walk, I learned of the death of a fellow HD support group member, a 20-year Navy veteran and airline pilot whose career and life were cut short by Huntington’s disease. He was just 65.

“Damned disease finally won,” his mournful wife wrote me in an e-mail.

As on countless occasions in my battle against HD, I had to overcome a sense of hopelessness, which threatened to overpower all of the good feelings about the research and the Hope Walk.

At the Hope event, I hugged our departed friend’s wife. Everybody held a moment of silence for him.

Before setting out on the walk, I guided one of our team members, a ninth-grader with a passion for science and technology, over to the area where employees from walk co-sponsor Vertex Pharmaceuticals were congregating.

I introduced him to Paul Negulescu, the Vertex vice president of research, and mentioned that he aimed to become a researcher.

Paul invited him to visit the Vertex facility and, in the future, perhaps contribute as an intern.

“I want to cure diseases,” the budding scientist told me during the walk.

Our cause had lost a warrior, but the Hope Walk had helped prepare another to do battle.

(Below see other photos from the Hope Walk.)

"Serbin Family Team" members (left to right): friends Sofia, Jessica, Alejandro, and Victoria along with Ken Serbin, with San Diego skyline in background

"Serbin Family Team" members James Kohn (left), Ami Carpenter, and Ken Serbin at finish line

Vertex Vice President of Research Paul Negulescu (left), Ken Serbin, and Vertex Vice President, Biology, Beth Hoffman

"Team Vertex" and friends with San Diego-Coronado Bridge in background