After a difficult year for the Huntington’s disease cause, CHDI chief scientist feels ‘reinvigorated’ and ‘optimistic’ about quest for therapies

 

Having faced negative results in two key clinical trials a year ago while battling the coronavirus pandemic, the Huntington’s disease community has renewed the quest for therapies (treatments).

 

A vital sign of this: despite initial fears about the omicron variant of COVID-19, the 17th Annual HD Therapeutics Conference took place ­from February 28-March 3 at the Parker Palm Springs hotel in Palm Springs, CA. The 305 fully vaccinated attendees gathered under a massive tent, which allowed social distancing and provided good ventilation.

 

Shortly after the March 2020 conference, much of the world went on lockdown to avoid the ravages of the virus, pushing the 2021 conference online.

 

“I don't think it's hyperbole to say that coming here for this conference in person feels like a rebirth,” said Robert Pacifici, Ph.D., in a half-hour interview with me on March 4. “It's been a hard couple of years for everybody, but for the Huntington's disease community in particular.”

 

Dr. Pacifici is the chief scientific officer of the conference sponsor, CHDI Foundation, the nonprofit virtual biotech entity geared solely towards finding HD therapies. CHDI is the largest private funder of HD research.

 

In March 2021, the community “learned that two of the really well thought-out and very rational clinical trials for Huntington's disease had been halted and it dashed a lot of people's hopes,” recalled Dr. Pacifici, referring to GENERATION HD1, the largest clinical trial in HD history, run by Roche, and two smaller trials with a similar drug run by Wave Life Sciences.

 

Those results “must have been devastating” for people awaiting an “efficacious treatment,” Dr. Pacifici continued. “But we do what the Huntington's community always does: we persevere, we lift ourselves up by our bootstraps, and we go forward.”

 

Witnessing a “bunch of reasons” for hope about therapies at the conference, Dr. Pacifici declared, “I'm reinvigorated and very optimistic.”

 

For an overview of the conference and my interview with Dr. Pacifici, watch the video below.

 

 

Above, HD Therapeutics Conference attendees view scientific posters presenting new research, and, below, watch one of the many presentations at the four-day event (photos by Gene Veritas, aka Kenneth P. Serbin).

 

 

Learning from last year’s setbacks

 

At the Therapeutics Conference, Roche elaborated on new data from GENERATION HD1 and its plans to develop an improved clinical trial. Wave provided an update on its new early-stage trial, SELECT-HD.

 

Both firms use gene silencing drugs to attempt to reduce the amount of the toxic huntingtin protein in the brain (called huntingtin lowering). Both seek to build on the lessons learned from the 2021 setbacks.  (Click here to read about Roche’s recent announcement and here about Wave’s new trial.)

 

“I'm heartened that there's still a lot of enthusiasm for the huntingtin-lowering approach,” Dr. Pacifici observed. “There's actually a very impressive portfolio of other companies, therapeutic modalities, and approaches to huntingtin-lowering.”

 

Other plans to attack the mutant protein

 

PTC Therapeutics and Novartis Pharmaceuticals presented updates on their respective ongoing clinical trials using different huntingtin-lowering approaches. Whereas Roche and Wave drugs were administered via an uncomfortable spinal tap done at a clinic, PTC and Novartis use so-called small molecules: pills.

 

Besides the obvious convenience, such small-molecule drugs offer other key advantages, Dr. Pacifici explained.

 

“We know that mutant huntingtin is expressed everywhere [in the body] and so it’s good to know that you can lower it everywhere with a small molecule,” he said, noting that dosages can then be calibrated to achieve different lowering effects.

 

A higher dose creates more lowering, while a lower dose lessens it, Dr. Pacifici explained.

 

“From a safety perspective, if we ever found a long-term problem with huntingtin lowering, you can stop taking the compound and let the huntingtin come back so that then you can decide,” he continued, referring to a practice called picket-fence dosing, in which patients stop and restart dosing as needed.

 

Triplet gears up to test its approach

 

With no guarantee that reducing the toxic protein will result in an effective treatment, the Huntington’s field has purposefully diversified.

 

A key example is the work of Triplet Therapeutics. Triplet focuses on somatic expansion (also known as somatic instability), the tendency in HD of the already expanded (and therefore mutant) huntingtin gene to continue growing in length with age. The greater the expansion, the earlier the impact of the mutation on brain cells. This process is governed by recently discovered modifier genes that slow or hasten disease onset. (Click here and here to read more.)

 

“That's what actually causes the cells to malfunction, to die, and eventually leads to the underlying physiology of Huntington's,” Dr. Pacifici said. “So, not surprisingly, that gives us another therapeutic handle. Can we slow down that somatic instability?”

 

At the conference, two Triplet scientists presented a preliminary analysis of data from SHIELD-HD, a research study of 70 presymptomatic and early-disease-stage carriers of the HD mutation. SHIELD-HD is furnishing data for a clinical trial of Triplet's drug candidate, TTX-3360, aimed at blocking somatic expansion and, therefore, potentially delaying or avoiding HD onset.

 

Triplet Therapeutics scientists Irina Antonijevic, M.D., Ph.D., the chief medical officer (right), and Peter Bialek, Ph.D., senior director of translational science, after their presentation at the HD Therapeutics Conference (photo by Gene Veritas)

 

Founded in 2018, Triplet has used the science of somatic expansion and HD modifier genes to move with “record-breaking speed” towards a clinical trial, Dr. Pacifici said.

 

In a brief interview after the Triplet presentation, Irina Antonijevic, M.D., Ph.D., the company’s chief medical officer, confirmed that it will file a Clinical Trial Application this summer for permission to start a Phase 1 dose escalation clinical trial of TTX-3360, mainly to test safety and tolerability. Regulatory agencies can take a few months to review the application, after which the firm could start recruiting people with HD.

 

“We’re very excited,” Dr. Pacifici said. “The whole area of somatic instability is a great complement to huntingtin lowering. It's possible that eventually, if God forbid, huntingtin lowering turns out not to be viable, we've got a great backup plan. But even if it is, these things could actually synergize with each other. I could imagine people in the future being treated with a combination of therapies that address both of these things – lowering the huntingtin protein, but also preventing additional somatic instability.”

 

A future article will explore the SHIELD-HD presentation and Triplet’s clinical trial plans.

 

The value of family participation

 

Most of the conference presentations focused on human data, as opposed to research in animals. Dr. Pacifici pointed out that many advances in HD research result from the participation of thousands of gene carriers in studies and clinical trials.

 

“I appreciate that families are willing to give their time, their blood, their urine, and the travel, the poking, the prodding they're going through,” Dr. Pacifici said. “I want to express my heartfelt gratitude. This year, more than ever, I guess I'm happy to say I told you so, meaning that I always encourage people to participate and we're now seeing the fruits of that participation. We now have the evidence that those samples are being used judiciously and are providing unparalleled value.”

 

Dr. Pacifici also pointed to the steadfast commitment of both scientists and families to HD research during the pandemic, which “required people taking risk and going into the clinics and the labs.”

 

“Hang in there, be resilient, participate when you can,” Dr. Pacifici concluded, because a “really talented, committed global group of passionate drug discovery professionals would love nothing more than to deliver what you need so desperately, which are effective treatments for Huntington's disease.”

 

For my coverage of the start of the conference, click here.

 

For additional coverage, visit HDBuzz.

Happy Thanksgiving! And hail to the pharmaceutical and biotech industries – and the scientists!

Thanksgiving this year is going to be radically different for many Americans, including my family.

 

I will celebrate my favorite holiday just with my wife Regina, home in San Diego.

 

As it has for many Americans, the COVID-19 pandemic has prevented us from hosting our usual small group of friends.

 

After eating a healthy brunch, we plan to have a Zoom call with our HD-free “miracle” daughter Bianca, a junior history major at the University of Pennsylvania. We are ever thankful that Bianca did not have to face the devastating possibility of juvenile HD. We will miss her, but are reassured knowing that she will spend the day with her boyfriend and his immediate family in the East.

 

We also hope to Zoom with some of our local friends. 

 

However, despite the terrible pall cast by the pandemic over the 2020 holiday season, I feel extremely optimistic that researchers will find a highly effective vaccine for the coronavirus.

 

The announcements of preliminary data by Moderna and the team of Pfizer and BioNTech revealed that their vaccine candidates reduced COVID-19 infections by 95 percent in clinical trials.

 

Dr. Anthony Fauci, the director of the National Institutes of Allergies and Infectious Diseases (NIAID), described the Moderna data as “stunningly impressive,” noting that he would have settled for 70-75 percent efficacy in a vaccine.

 

“It is really a spectacular result that I don’t think anybody had anticipated would be this good,” Dr. Fauci said. He had similar praise for the Pfizer/BioNTech data.

 

Both of these trials use genetic approaches: they introduce the virus’s own genes into cells to provoke an immune response.

 

According to the New York Times’ Coronavirus Vaccine Tracker, several dozen other companies have embarked on clinical trial programs using some form of approach based on genetics or other cutting-edge strategies. Only ten projects are making vaccines using the traditional approach of injecting weakened or dead coronaviruses.

 

In all, scientists are testing 54 vaccines in clinical trials, and at least 87 more are under investigation in animals.

 

Genetics-based approaches are familiar to the HD community, where researchers have investigated the potential of gene silencing drugs for more than a decade. Researchers in the lead program, Roche’s historic GENERATION HD1 Phase 3 clinical trial, hope to analyze data in 2022. 

 

When I heard of the initial reports of Moderna’s genetics-based approach, I felt deeply confident that humanity would ultimately defeat the coronavirus. 

 

The potentially record speed in getting a vaccine to the world is testimony to the ingenuity, dedication, and focus of the biotech and pharmaceutical industries, which I have observed with deep interest in my nearly quarter century as an HD advocate and student of the science – and as a writer summarizing the science in simple terms.

 

In October, posting on Facebook an article on the bold Triplet Therapeutics clinical trial program – yet another genetics-based effort – I wrote the following: “Hail to the many imaginative and hard-working companies in America’s pharmaceutical industry!”

 

I also salute the scientists involved, and the many pharmaceutical and biotech firms of other nations engaged in the fight against COVID-19 and HD.

 

Also, we must not forget the millions of doctors, nurses, and other healthcare workers and first responders who have heroically attempted to hold the line against COVID-19, thus giving the researchers the time necessary to develop the vaccines.

 

Thanksgiving is our quintessential American holiday. This year, with the pandemic, it takes on a global significance. Across all cultures and nations, the virus has led us to realize once again our common humanity – and the collective efforts needed to safeguard life for all.

 

 

Photo by Bianca Serbin, taken in fall 2009 at the San Diego Botanic Garden (click here to read more).

In the pandemic, we need to rediscover patience and grasp our responsibility

In this time of pandemic, the virtue of patience is paramount. So is the need to grasp our impact on the history of the planet and its effect on our lives. We who are afflicted with rare diseases have already had to learn many hard life lessons, which apply to the vital efforts to confront the coronavirus. 

As we mark Huntington’s Disease Awareness Month, we recall how many in the HD and other neurological and rare disease communities have demonstrated great fortitude and also patience as we await effective treatments. Since learning of my mother’s diagnosis with HD in 1995 and my positive test for the mutation in 1999, I have worried about the inevitable onset of symptoms and yearned for a successful clinical trial to produce a drug to stave off the disease or ameliorate it.

“HD warriors” like my mother and caregiver father (both deceased) have had to confront the disease on a daily basis for a decade or longer. 

Drugs like tominersen, the gene-silencing compound now in a historical Phase 3 clinical trial run by Roche, require painstaking development and often well over a decade to reach the market.

The tominersen project began in 2007, and Roche expects to analyze Phase 3 data in 2022. (Tominersen was previously known as RG6042 and, before that, as IONIS-HTT_Rx.)

The best-case scenarios for an effective and safe COVID-19 vaccine for the general public point to some time in 2021. 

“What people don’t realize is that normally vaccine development takes many years, sometimes decades,” Dan Barouch, M.D., a virologist at Beth Israel Deaconess Medical Center in Boston, stated in a news report. “And so trying to compress the whole vaccine process into 12 to 18 months is really unheard-of.”

A vaccine might never be found; after decades of intense research, science still has not developed one for AIDS.

Drug development requires precision and patience.

Possible hope from new drug development approaches

That said, by dint of biomedical progress (but lacking overall preparedness for a pandemic), the current worldwide effort could take place more rapidly than previous drug-development work.

With positive results in the very early stage of its vaccine program, drug maker Moderna, Inc., is using an RNA-based approach to attempt to block the actions of the coronavirus.

Ionis Pharmaceuticals, Inc., the developer of tominersen, is also looking into ways its drug technology “could benefit COVID-19 patients, first by looking at our existing pipeline to see if any clinical or preclinical drugs would have a use in treatment in either the disease, or more likely the complications of the disease arising from the acute respiratory syndrome,” Eric Swayze, Ph.D., the firm’s senior vice president of research, wrote in an e-mail to me on May 8. Ionis designs drugs using antisense oligonucleotides (artificial strands of DNA), a form of gene silencing technology.

“In the 2002/2003 SARS epidemic we did done some work with ASOs targeting both the coronavirus itself as well as host factors, and had preliminary hints of activity [effect],” Swayze added. “Because of this, we are making newer generation ASOs targeted to the SARS-CoV-2 [COVID-19] virus as well as host factors that contribute to the infection and disease. 

“We plan to work with collaborators who have the capability to test our lead ASOs in virus cultures. We believe that our recent pulmonary program advances position us to quickly move forward, provided that our drugs look promising. However, we feel this remains a high-risk discovery project, with many challenges ahead.”

Behind the reaction against lockdowns

However, despite the need for a long-term fight against COVID-19, only a few weeks after lockdowns began, tiny groups of purported “protestors” appeared demanding to “open up” states. They were egged on by President Donald Trump, who has declined to marshal national resources against the virus, and organized by conservative groups.

I have wondered: What if Americans had wanted to give up only three weeks after the 1941 attack on Pearl Harbor?

The initial impatience about COVID-19 was clearly politically motivated. Since then, some criticism of lockdowns results from growing economic hardship: with a 14.7 percent unemployment rate, the U.S. has lost the greatest number of jobs since the Great Depression of the 1930s. In addition, many small business owners have had to curtail their work or even shut down completely.

The pain hits professors and students

The economic pain has hit American universities such as my employer, the University of San Diego (USD), which switched to remote, online instruction in mid-March. Confronting an unexpected deficit, the president has announced a 50 percent cut in retirement benefits and a salary and hiring freeze.

There is no consensus nationally on how to resume classes in the fall, with leaders of different campuses struggling with uncertainty. The nation’s largest public university, California State University, for example, has announced, that its campuses will move nearly all instruction online.

With USD’s dependence on tuition for institutional survival and its reputation for high-quality instruction in relatively small classes in small classrooms, the administration has launched a still inchoate plan to reopen for the fall semester early, in mid-August. According to administrators, because of the loss in student fees, going remote again would extend losses by tens of millions of dollars, forcing possible layoffs and furloughs of some instructors and employees, an increased teaching load for the main faculty, and other types of cutbacks.

Many professors, including myself, fear returning to campus so soon; in normal times, packed dorms, classrooms, and other facilities (and student parties administrators can’t control) provide ideal conditions for a virus to spread. Though young people are less likely to suffer from coronavirus symptoms, some do get serious cases, and asymptomatic people can of course spread the virus to others more vulnerable.

Universities and their employees will seek to implement social distancing, testing for COVID-19, and other measures. Ultimately, depending on the course of the pandemic, many might have to resort again to remote learning.

We cannot return to ‘normal’

In fact, three in four Americans have supported social distancing and wearing masks.

Without good health, we are restricted economically, as the HD community knows so well.

I believe that the impatience comes in part from our culture of instant gratification, epitomized by online shopping and overnight delivery. Another part relates to political orientation, with Republicans favoring a more rapid opening than Democrats (for one analysis, click here).

I think many people – myself included – wrongly thought that, after a month or two of lockdown, we would return to “normal.”

However, as New York Governor  Andrew Cuomo put it on April 1, “I don’t think we get back to normal. We get to a new normal.” As a result of the crisis, society will undergo a “transformation,” and we must assure that it be “positive and not negative,” Cuomo urged.

“I fear that the resumption of normality would signal a failure to learn,” commented Pulitzer-Prize-winning medical writer Siddhartha Mukherjee, M.D. “We need to think not about resumption but about revision.”

He added, with reference to how the drive for instant success has exacerbated the pain of the pandemic: “To what extent did the market-driven, efficiency-obsessed culture of hospital administration contribute to the crisis?”

The perspective of Big History

Cuomo echoed the point that professional historians like me make to students and readers of our books: history is ever-changing, often with great progress, but also devastating setbacks, including world wars, plagues, and inhumane practices like slavery.

I teach a course called “Big History: From Cosmos to Cannibals,” which begins with the start of the universe and ends with the dawn of the modern era: Europeans' conquest of the Americas, beginning in the late 1400s and quickly causing epidemics of Old World diseases in which tens of millions of native Americans died in the hemisphere – a very poignant point of comparison with the pandemic this past semester. A field that has emerged recently, Big History embraces the idea that human development must be understood in the context of physics, biology, evolution, and the transition from small bands of hunter-gatherers to cities with millions of people.

Over the past several years, my classes have focused on how we now live in the Anthropocene, an era in which humans have taken control of the earth’s systems (atmosphere, oceans, land, life, and others).

Human agency has led to global warming, probably a more daunting challenge to humankind than coronaviruses, and many other threatening phenomena.

Human control has contributed to the crisis

In fact, some commentators have asserted that the pandemic has resulted from the humans’ super-control of the earth and our encroachment on the last vestiges of nature in areas such as the Amazon rainforest (for some examples, click here, here, and here).

Deforestation (for cash crops and cattle), mining, a growing population, and the expansion of urban areas have put the environment and the species therein under greater stress, making them more susceptible to viruses and zoonosis (jumping of a virus from one species to another, including humans).

Human domination of the planet has intensified over the past several decades. I witnessed the devastation firsthand of the Amazon in 1988 and 1990, during my time in Brazil as a graduate student. I saw gold prospectors who penetrated the deepest recesses of the forest, using clandestine airstrips. I also viewed up close how many square miles of trees had been cut down.

Above, using modern equipment, men prospect for gold by excavating the floor of the Amazon rainforest in Brazil, 1988 (photo by Gene Veritas, aka Kenneth P. Serbin). Below, Gene Veritas (wearing sunglasses) with workers at the mining site (personal photo).

Reconnecting with ourselves, and the planet

In my Big History course just concluded this semester, we were all deeply saddened by the onset of the pandemic. However, in the context of history, a devastating viral outbreak was highly likely. Leading scientists have also warned the world for decades.

The pandemic serves as a global alarm. The Earth is a system, and it is crying out against our dangerous intrusions into rainforests and other attacks on the environment. Ironically, with the decrease in vehicle traffic, the vast reduction in pollution gives us a glimpse of the air quality we once had and must achieve again to stem the tide.

A key lesson of my Big History course is that the modern world led humans to think they were separate from nature, but, in reality, we are ever more interconnected. The pandemic will perhaps force humanity to rediscover our identity (for some, a spirituality) of being one with nature. We are part of the Earth, not over and above it.

As Dr. Mukherjee pointed out, the virus has laid bare many things, such as the inequality of our health system. It has also laid bare our impatience. To overcome the virus, we need to regain patience and, along with it, humility and respect for the planet.

As Dr. Mukherjee and others have urged, we also need to learn from this crisis and make better policy choices for future threats of all types.

(Disclosure: I hold a symbolic amount of Ionis shares.)

Combatting the pandemic, Roche also forges ahead with critical Phase 3 Huntington’s disease clinical trial

Using its expertise to combat a coronavirus pandemic that has left more than 180,000 people dead worldwide and a third of the earth’s people on lockdown, pharmaceutical giant Roche is also forging ahead with its Phase 3 clinical trial for the Huntington’s disease gene silencing drug RG6042, now known by the generic name tominersen.

The final step in a clinical trial program, Phase 3 tests the efficacy of a drug. A successful Phase 3 allows a pharmaceutical company to apply to regulatory agencies for permission to market the drug. In a time of “social distancing” and a shutdown of normal life, Roche and HD clinical trial administrators are seeking to mitigate the risks associated with the spread of COVID-19, the disease caused by the coronavirus.

In an April 20 letter to the global HD community, Roche announced that it had completed recruitment for the trial, GENERATION HD1. A total of 791 symptomatic volunteers across 18 countries have been enrolled, just ten fewer people than Roche projected after the trial got under way last year – almost 99 percent of the target.

“This achievement is a result of the HD community’s commitment from the beginning, and we are very grateful to all trial participants, their families, the clinical trial sites and staff, and the broader HD community who have supported the design, initiation and recruitment phases of the study,” Roche global patient partnership directors David West and Mai-Lise Nguyen stated in the letter.

West and Nguyen reassured the community that “tominersen studies are ongoing at clinical trial sites around the world,” and, in collaboration with local health authorities, “ensuring patient safety and data integrity throughout the studies given the ongoing impact of COVID-19.”

On February 27, Roche announced the generic name for its HD gene-silencing drug candidate RG6042, formerly known as IONIS-HTT_Rx, developed by Ionis Pharmaceuticals, Inc. With assistance from Roche, Ionis ran the successful Phase 1/2a trial for the compound, shown to be safe and tolerable in trial participants. It also lowered the amount of mutant huntingtin protein, a major suspect in the disease, in volunteers’ cerebrospinal fluid. (Slide courtesy of Roche.) 

Aiming to analyze data in 2022

“Given the dynamic situation with COVID-19, we decided to close recruitment at 791 participants globally in order to avoid additional pressure on clinical trial sites who were screening potential participants,” they added, noting that the number of participants is “sufficient” to assess tominersen’s efficacy.

Roche is “working closely with the research teams, trial sites and local authorities to reduce any new risks posed by COVID-19 and ensure the trial can continue as long as it is safe to do so,” the letter stated. Roche advises participants to “discuss individual circumstances with their respective study sites.”

“Where patients and families can no longer go into [the] hospital to receive treatment or assessments, research teams will be in close contact over the phone to monitor their health and discuss any potential adverse events or any other issues,” the letter added.

Roche expects to complete the trial and start analyzing data by 2022, after each of the volunteers has completed the 25-month program involving intrathecal (spinal) injections of tominersen or a placebo, tests, medical evaluations, and digital monitoring, West and Nguyen stated.

If tominersen demonstrates efficacy and safety, Roche will submit applications to national health authorities to obtain approval as a treatment.

“During these exceptional times, we continue to consider how we can best support the community and welcome any suggestions,” the letter concluded.

In an April 21 e-mail to me, West noted that GENERATION HD1 recruitment was “completed within expected timelines,” unaffected by the COVID-19 crisis. In line with plans announced last October, Roche will also extend the study to China “as soon as possible,” West added.

Combatting COVID-19

The April 20 statement on GENERATION HD1 followed a general statement by Roche on March 19 discussing the March 11 announcement of the pandemic by the World Health Organization and the company’s efforts to combat it.

“We recognise that the public and private sectors across the globe need to work together to help effectively manage this developing situation,” said the statement, noting that Roche was engaged in developing a COVID-19 “diagnostics test which was granted Emergency Use Authorization by the U.S. Food and Drug Administration.”

Scientists, physicians, and public officials have stated repeatedly that vastly increased testing for the virus is needed in the battle against the pandemic.

Roche also confirmed initiation of COVACTA, a global Phase 3 clinical trial to evaluate the safety and efficacy of its rheumatoid arthritis drug Actemra/RoActemra in treating patients with severe COVID-19 pneumonia. The study started to enroll patients on April 3, with a target of 330 globally, including the U.S., Canada, and Europe.

Roche is also examining other drugs in its portfolio for potential testing to treat COVID-19.

(Click here to read more on Roche’s efforts against the coronavirus.)

A key supplementary trial

The February 27 announcement of the generic name tominersen took place at the 15th Annual Huntington’s Disease Therapeutics Conference, sponsored by CHDI Foundation, Inc., in Palm Springs, CA. (For an overview of the conference, click here.)

Scott Schobel, M.D., M.Sc., Roche’s associate group medical director and medical leader of the GENERATION HD1 effort, introduced the name when presenting the preliminary results of the so-called open label extension study (OLE) study of the compound. For 15 months, Roche continued to give the drug to all of the 46 participants of the successful Ionis trial, completed in December 2017. That same day, Roche posted the slides of Dr. Schobel’s presentation on its website.

The OLE reinforced the findings of the Phase 1/2a trial, which showed tominersen to be safe and tolerable in trial participants. Tominersen also lowered the amount of mutant huntingtin protein, a major suspect in the disease, in volunteers’ cerebrospinal fluid.

Also, when still in progress in early 2019, the OLE led Roche to temporarily halt GENERATION HD1 to redesign it in line with the OLE’s promising early data. 

In the original GENERATION HD1 design, participants would undergo monthly spinal tap (lumbar puncture) procedures over 25 months. One-third of participants would receive tominersen each month and one-third every other month. Another third would get a placebo.

In the updated trial, which resumed in June 2019, Roche decreased lumbar punctures to once every other month over the same period of time. In this revised design, one-third of participants are receiving tominersen every other month and one-third every four months. Another third will receive a placebo every other month. (Click here to read more.)

Less frequent dosing eases the burden on participants, their families, and clinical trial administrators.

The OLE also investigated potential biomarkers (signs of the disease and drug efficacy) for use in GENERATION HD1.

The OLE formed part of Roche’s strategy for skipping the usual Phase 2 trial to test efficacy and entering directly into Phase 3 to confirm efficacy in a larger population (click here to read more).

Scott Schobel, M.D., M.Sc., presenting open label extension study data for tominersen at the 15th Annual HD Therapeutics Conference (photo by Gene Veritas)

The ‘ultimate’ question: efficacy

After his presentation, Dr. Schobel met briefly with HD advocates to discuss his presentation and GENERATION HD1.

For the HD community, the takeaway message was the OLE’s confirmation of a less frequent dosage, and its helpful data for GENERATION HD1. Except for one person who decided to drop out to take a trip around the world, all of the OLE participants had continued taking the drug, putting them now at 20 months of follow-up, he explained.

Roche has great “confidence” in the sufficiency of the less frequent dosing in GENERATION HD1, Dr. Schobel emphasized.

With the OLE, Roche has “been able to learn” and apply it directly to GENERATION HD1 “in a way that we couldn’t have done if did a more traditional drug development path, which we feel great about,” he said.

What remains is the “ultimate” question: will tominersen be an effective treatment?

“We’re well-positioned with GENERATION HD1 to answer that question,” Dr. Schobel concluded.

If the trial is successful, tominersen will become the first treatment to slow, halt, and perhaps even reverse the symptoms of Huntington’s disease. 

(I hope to report soon on other ways in which COVID-19 has impacted the HD community and research.)

(Disclosure: I hold a symbolic amount of Ionis shares.)

Giving back during the COVID-19 pandemic

Many advocates for Huntington’s and other rare diseases work passionately and selflessly for their causes.

Now, as the coronavirus pandemic rages, more and more people around the globe want to give back. 

We are all witnessing the testimonies of the doctors, nurses, and other healthcare workers who offer front-line care for the patients hit with COVID-19, the disease caused by the virus.

As a Huntington’s gene carrier who lost his mother to the malady, I, too, want to help – in part because the crisis has postponed or forced online so many aspects of the HD cause (more on this in an upcoming article).

HD activists can and should do their part to help alleviate this crisis!

Preparing for a surge of patients

Worried about the flood of reports about shortages of personal protective equipment (PPE), I reached out to Yale University class of 1982 colleague and freshman roommate Peter S. Kieffer, M.D., an emergency room pediatrician, to see if I could help, perhaps by organizing an online campaign to support him and his institution. Dr. Kieffer works at HSHS St. John’s Hospital in Springfield, IL. An assistant professor at the Southern Illinois University School of Medicine, he also advocates for the chronically mentally ill through Independence Center. 

In 2014, after decades out of touch, Dr. Kieffer wrote in an e-mail that he had discovered this blog and my family’s struggle against HD.

“My heart goes out to you and your family as I have been long aware of the challenges of Huntington's disease, its genetic transmission, and the implications of early testing but have never known anyone personally with the diagnosis,” Dr. Kieffer wrote.

Since then, he and his family have donated generously to the Serbin Family Team in the annual Hope Walk of the San Diego Chapter of the Huntington’s Disease Society of America (HDSA). Several years ago, they visited us during their vacation in the area.

In his response to my March 28 e-mail, Dr. Kieffer explained that “physicians in rural Illinois have had more time to prepare for COVID-19 than our colleagues in big cities.”

“Numbers were small, now cases are becoming more frequent, and we are preparing for a surge in the next few weeks which could very easily surpass the ICU bed and ventilator capacity of our two hospitals,” he wrote. “However, Governor [J. B.] Pritzker's early shutdown may help blunt that curve. Although COVID-19 typically sickens children with less severity, they could still pass it to a white-haired pediatrician like myself! Fortunately, we still have enough PPE for what we need.”

So far, Dr. Kieffer has treated a young child who was a “Patient Under Investigation,” although tests have not yet confirmed COVID-19 in any of his patients, he wrote in an e-mail today.

Dr. Kieffer agreed to contact me should his institution need aid. I know that I personally cannot send PPE or medical equipment, but raising awareness about the local predicament and raising funds could be a way to assist.

Peter S. Kieffer, M.D. (photo by Southern Illinois University School of Medicine)

Donating critically needed blood

There are other ways I - and you - can help now.

After seeing an American Red Cross blood drive appeal on TV a couple weeks ago, I scheduled a donation for March 30. 

Last week, I suspended my minimal meat diet to raise the iron levels in my blood, as recommended by a Red Cross employee, who set me up for a “power red” donation (double the number of red blood cells).

That employee also told me of a critical shortage of blood, as reported by the Red Cross and in the media (click here to read more).

At the donation center, an employee took my temperature at the door, to make sure I had no fever and, therefore, possible COVID-19 symptoms. Donors were spaced about eight feet apart, to avoid contamination, and the nurses and other workers wore not only the typical gloves, but also masks.

Unfortunately, in a pre-donation pin-prick blood test, I fell just shy of the necessary iron level for a power red.

However, I was able to make a simple “whole blood” donation.

Gene Veritas, aka Kenneth P. Serbin, at an American Red Cross blood donation center in San Diego (photo by Gene Veritas)

Running risks for the common good

On the way home I thought: in any public place, we all run the potential risk of contracting the coronavirus, even at a facility like the Red Cross. 

I washed my hands very thoroughly, twice at the facility, then again at home. None of the donors, nor I, wore a mask. However, I may on future trips to public places, given the increasing number of reports about their effectiveness in blocking droplets that might contain the virus.

Like so many other HD gene carriers, I’ve spent many moments monitoring myself for symptoms. Now, I’ve started doing that for the virus.

However, physicians like Dr. Kieffer, first responders, grocery store workers, and so many others risk their health daily for the common good.

We all need to embrace the spirit of Dr. Kieffer’s words to me, echoing one of the signs at the Red Cross: “Thanks so much for your life-giving donation!”

Above, Gene Veritas' blood pack, and below, Gene Veritas in a donor chair at the American Red Cross (photos by Gene Veritas)