The best news for the Huntington's disease community since the discovery of the gene: Ionis trial data revealed, Roche confirms jump to Phase 3

Researchers revealed impressive, if not conclusive, additional information at CHDI Foundation's 13th Annual Huntington’s Disease Therapeutics Conference yesterday regarding the historic Ionis HD clinical trial: the drop in mutant protein observed in the cerebral spinal fluid (CSF) of participants corresponds to as much as an 85 percent decrease in the cortex of the brain, head physician Dr. Sarah Tabrizi announced.

It’s the best news the HD community has received since the publication of the research confirming the discovery of the gene 25 years ago this month. As scientists have observed, it’s also a major step for disease and drug research in general.

“The magnitude of mutant huntingtin [protein] reduction observed exceeds the effect needed for disease modification in animal models,” Dr. Tabrizi, of University College of London (the lead clinical trial site), told an audience of some 350 scientists, drug company representatives, and HD advocates at the conference in Palm Springs, CA.

Dr. Sarah Tabrizi presenting the IONIS-HTTRx trial data on March 1, 2018 (photo by Gene Veritas, aka Kenneth P. Serbin)

Ionis officials announced in December that the Phase 1/2a trial for the gene-silencing drug IONIS-HTT_Rx “substantially exceeded our expectations” in safely reducing the mutant huntingtin in the CSF.

For the first time, Dr. Tabrizi’s presentation (plus an Ionis press release) specified the level of huntingtin reduction.

During the clinical trial, participants received the drug via spinal injections, and doctors measured the drug’s ability to reduce the protein by extracting CSF samples.

IONIS-HTT_Rx lowered mutant huntingtin an average of 40 percent, with a maximum reduction of 60 percent. As Dr. Tabrizi explained, projecting from the numerous, painstaking animal studies done by Ionis, the reductions in the cortex range from 55-85 percent.

Frank Bennett, Ph.D., Ionis senior vice president of research and the franchise leader for neurology programs (left) and Anne Smith, Ph.D., Ionis director of clinical development (middle), confer with Dr. Tabrizi moments before the two women's historic presentation of the IONIS-HTTRx trial data. Dr. Bennett led the Ionis efforts to develop the drug (photo by Gene Veritas).

The cortex – along with the striatum, which is critical to motor control and managing the reward system – is the area of the brain most affected by HD. It is the most developed area of the brain, the source of thought and language, abilities severely hampered by HD.

Watch Dr. Tabrizi in the short video excerpts below explain this data and thank the 46 brave clinical trial volunteers and the many others involved in the effort. I also recommend watching the full video – which includes further trial data and a helpful overview of the project by Anne Smith, Ph.D., of Ionis – by clicking here.

 Ionis trial reduces bad Huntington's disease protein from Gene Veritas on Vimeo.

The plans for RG6042, the drug’s new name

The presentation by Drs. Smith and Tabrizi – the first public presentation of the trial data – can perhaps help inspire the HD community and researchers to become engaged in the next, crucial step: testing the drug’s efficacy.

Based on its partnership agreement with Ionis, Swiss pharmaceutical giant Roche, which now holds the license to the drug, will carry out a longer trial with hundreds of participants, including sites in the U.S.

The main question: will symptoms of this progressive, deadly disease stabilize, or even be reversed?

In an interview at the conference, Roche officials told me that – as Ionis had indicated – the company would take the unusual step of skipping a Phase 2 trial (testing efficacy for the first time) and going directly to a Phase 3 (confirming efficacy in hundreds, or more, participants).

They pointed to the excellent results of the Phase 1/2a trial; Ionis’ superb development of the drug; the nonprofit CHDI’s expertise and leadership; and the enthusiasm from – and urgent need of – the HD community.

Roche has officially changed the name of IONIS-HTT_Rx to RG6042. “R” stands for Roche, and “G” for Genentech, a major U.S.-based pharmaceutical company acquired by Roche in 2009 for $46.8 billion. The number 6042 is a standard drug number assigned by the company. If Phase 3 is successful, a drug issued for commercial sale will get a brand name.

All U.S-based Roche personnel and products still use the name Genentech.

Roche has not yet determined a start date or timeline for Phase 3. I will provide a detailed report on the interview and Roche’s plans, and also my personal reactions to the conference, in upcoming articles.

Members of the Roche HD clinical trial team watch Dr. Tabrizi's presentation. From left to right, Scott Schobel, M.D., M.S., clinical science leader of product development; Lauren Boak, Ph.D., global development team leader; Erik Lundgren, lifecycle leader of the HD program; and Mai-Lise Nguyen, the patient partnership director for the HD program (photo by Gene Veritas). 

Time for excitement, but also caution

CHDI Chief Scientific Officer Robert Pacifici, Ph.D., called the results of the Ionis trial “incredibly exciting.”

However, he also cautioned the HD community.

“Drug discovery is a really time-consuming and inefficient process, and, sadly, fraught with many failures,” Dr. Pacifici said. “The first time you put something into people, no matter how prepared, you never know whether it’s going to be safe and well-tolerated. What the initial trial showed was that at those doses, with the route of delivery, with that population of folks, it is indeed safe and well-tolerated. (If it wasn’t, it would stop in its tracks.) Once you get to this stage, a lot of the uncertainty about timelines goes away.

“This is really the time to be incredibly careful and incredibly deliberate. It’s going to take a while now to orchestrate the Phase 3 trial. That’s the pivotal trial that tells you whether or not the drug works.”

Everything needs to be done “by the book” to get a really “conclusive result,” he added.

If the trial fails, it will still provide scientists and physicians with guideposts for future research and trials, he said.

“We owe a huge debt of gratitude to those patients who signed up for that initial trial,” Dr. Pacifici concluded. “It’s going to require not only more of that type of participation, but a lot of patience.”

You can watch my interview with Dr. Pacifici about the conference and the Ionis trial in the video below.

 A time for excitement, but also great care and deliberation from Gene Veritas on Vimeo.

* * *

Ionis hosted a live webcast at 11 a.m. Eastern Time today. A webcast replay, including slides with clinical trial data, are available by clicking here.

For detailed coverage of the HD conference presentations, visit hdbuzz.net.

Visit my Vimeo album, to be periodically updated in the coming weeks, for other presentations and interviews at the conference.

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

Ionis scientists provide initial assessment of successful Phase 1/2a Huntington’s disease trial and discuss next steps

After announcing December 11 that Ionis Pharmaceuticals’ gene-silencing drug for Huntington’s disease safely reduced the production of the toxic HD protein, company officials analyzed the firm’s successful Phase 1/2a clinical trial and discussed the next step: larger trials that are designed to test IONIS-HTT_Rx’s efficacy in alleviating symptoms by modifying the course of the disease.

I met with two lead scientists from Ionis’ HD team at company headquarters in Carlsbad, CA: Frank Bennett, Ph.D., Ionis senior vice president of research and the franchise leader for the company’s neurology programs, and Anne Smith, Ph.D., the Ionis director of clinical development and the individual responsible for the day-to-day management of the trial.

Drs. Bennett and Smith stressed that, because the two-year trial ended just last month, they could provide only an initial assessment of the results. The company plans to present detailed clinical trial findings at medical conferences in early 2018 and then publish the results in scientific journals.

Ionis will transfer administration of the next clinical trial phases to Roche, a key partner in the project since 2013. Roche now holds the license to IONIS-HTT_Rx, will lead further development, and handle all potential sales. Phase 1/2a took place in Canada, England, and Germany, but the next phase will have sites in the U.S. and other countries, to be determined next year by Roche. Ionis will continue to play an advisory role in the project.

“We are very appreciative of the community, and the patience that the community has exhibited,” Dr. Bennett said. “We understand how important this is for the HD community. We’re very pleased it’s going forward. The community has been very respectful towards the company and has allowed us to conduct this study in a way that was very robust.”

Drs. Bennett and Smith focused on how the trial revealed a reduction in the mutant huntingtin protein that “substantially exceeded our expectations,” according to the December 11 press release. The key, initial piece of trial data came from the measurement of the protein in the HD patients’ cerebrospinal fluid (CSF). Other trial data such as brain scans and blood samples will become available later.

IONIS-HTT_Rx and other Ionis drugs are antisense oligonucleotides (ASOs, artificial strands of DNA), which alter the expression of genes. In August 2016, Ionis and its partner Biogen actually halted a Phase 3 trial of an Ionis ASO in infants with spinal muscular atrophy (a motor neuron disease) because the drug was extending their lives. The FDA (Food and Drug Administration) approved the drug, with the commercial name SPINRAZA, in December 2016.

In October, Ionis and Biogen won a biotechnology prize for SPINRAZA (click here to read more). Ionis is also collaborating with Biogen to develop a drug for amyotrophic lateral sclerosis (Lou Gehrig’s disease).

Dr. Frank Bennett (left) with Gene Veritas (aka Kenneth P. Serbin) and Dr. Anne Smith (photo by Kristina Bowyer, Ionis)

Following are key excerpts from the interview.

Compelling changes in mutant huntingtin levels

GV: How did patients react to the intrathecal administration of the drug, that is, via a spinal tap?

AS: We didn’t hear from any of the physicians that there were any difficulties. There was probably some nervousness, but there were few side effects, and that ones they had were manageable. I think it’s telling that all 46 patients completed the trial.

GV: What was observed in the HD patients in this trial?

AS: We’re still in the process of getting these next waves of data in. That will come out over months. It’s important to recognize that the trial just ended in November. But at this stage we did see a promising safety profile, meaning that we didn’t have any clinical concerns with the drug.

We saw clear, compelling changes in mutant huntingtin levels in the CSF. It was sort of gravy in this study. It’s designed as a safety study. We didn’t know when we entered the study whether we’d be able to even measure mutant huntingtin in CSF. But it is the best evidence of target engagement that we have – meaning that it is evidence that the drug is doing what it ought to do.

We were pleased that the assay [lab test] was developed to the point that we could use it to measure mutant huntingtin. The test is relatively new and fortunately came online at about the right time that we needed it.

The label from the first vial of the Phase 1/2a clinical trial, administered in London, September 2015 (photo by Gene Veritas)

GV: The reductions of mutant huntingtin “substantially exceeded” your expectations. To what extent?

FB: When we began the program with Roche, we picked a target level of reduction of mutant huntingtin in CSF, and, based upon that, we would decide to go forward with the program [into the next phase].

We put the mutant huntingtin data at the top of the list, because it was the data that was going to drive a business decision from Roche, but also, importantly, it was the data that would help them design the next study. So we prioritized that as being the first thing we would look at. It’s the basis for telling us what are the doses that we should be using for the next study.

GV: So can you specify the amount of mutant huntingtin reduction?

FB: We’re going to save that for a medical meeting.

Phase 1/2a too early for improving symptoms

GV: You project from your pre-clinical animal studies that the level of reduction in the brain itself should be greater than what is seen in the CSF, correct?

FB: Yes. An important nuance for the community is that the level of reduction that we’re seeing in CSF is not a one-to-one correlation with the level in [brain] tissue, which is where you want the drug to be working. We haven’t proven it in patients, but we’re very confident that it will translate [into higher levels of reduction in the brain].

AS: We’ve tested this drug in several species and are able to understand that relationship between what you see in CSF versus what you see in [brain] tissue, which is why it was really important this assay [CSF measurement] was online. It really is a window into the brain.

To understand that relationship in animals, the animals have to be sacrificed, to measure the level in the [brain] tissue. So we won’t ever ‘prove’ it in humans, so to speak, but we have a good understanding of it through the animals. And that it’s consistent from species to species is comforting. We can draw a conclusion about what’s likely happening in the human.

GV: Many in the HD community want to know: in this trial, did you see any signs of disease modification? Were there any hints at all from the doctors or from the data?

AS: We get anecdotal reports from physicians, but this is a population with a high placebo effect. These are motivated and excited physicians and patients as well. So I wouldn’t read anything into that. It’ll be several months before we have an understanding, though I would really caution any expectations along those fronts, because this is a short-term study.

We’re not expecting to see any sort of disease modification, just because of the way the study was designed. We dosed for three months, but it wasn’t even full drug effect for three months, because you build up the effect. This is the precursor to what would be long-term dosing.

GV: Have you observed whether there was also a reduction in the wild type (normal) huntingtin protein that all HD patients also have?

FB: There isn’t a good assay [lab test] for measuring wild type at this point. We have the samples, and once the assay is robust enough, we’ll look at it. The team is working on it, as well as others.

GV: Were there any surprises in the data that you’ve seen so far?

FB: It’s only surprising that it’s worked as we predicted it would [laughter]. Oftentimes when you go from pre-clinical to clinical, things don’t quite work out as well. But the drug is doing what it should be doing, which is lowering mutant huntingtin in cerebrospinal fluid. I think it’s all very positive from that perspective.

Phase 2 versus Phase 3

GV: What have you learned that will be helpful in planning phase 2?

FB: We asked a lot of the sites and the patients – because we collected a tremendous amount of data from them – for data that will be useful in designing a Phase 3 trial. We wanted to figure out which of the clinical outcome measures, which of the imaging measures, is actually reproducible, robust, and sensitive, to make sure it’s not “noisy” data.

AS: Another important learning will be whether there are differences from site to site. In a multi-site, multi-country trial, if a particular test just doesn’t translate well to German, for example, then we’ll have learned that. We can spare Roche from collecting data that are difficult to interpret, because they’re difficult to operationalize across sites and countries.

GV: You said “Phase 3” and not Phase 2. Why?

FB: Yes. At this point, Roche has not made a final decision on the next step. One of the options being considered is going right to a Phase 3 study. There’s a trade-off. You can do a smaller Phase 2 study – get more data that make it more probable that you’ll be successful for the Phase 3 – or you can go directly to a Phase 3 study. Those are the decisions that Roche is looking at right now very carefully.

The plus side is: if they go right to Phase 3, it would accelerate getting the drug to market. When we’ve reviewed with them the size of the study and the time of the study, there’s not a big difference between doing a Phase 3 and doing a more traditional Phase 2 first. It’s more expensive to go right to Phase 3, but it would save a lot of time.

GV: For an entity such as the FDA, is it okay to go from a Phase 1/2a to a Phase 3?

FB: The FDA will pay a lot of attention to the safety of the drug which – so far, knock on wood – looks very good. And then they leave it to the sponsor whether they want to risk the program. They may advise – because they ultimately want the drug to be successful, too – that this isn’t the best thing to do, but ultimately that’s the drug company’s decision. Roche will engage with the FDA.

GV: What is leading Roche to think it could maybe go directly to a Phase 3?

FB: It’s safety and tolerability [shown in Phase 1/2a], and the fact that we now know what dose of the drug produces this level of huntingtin lowering. Without that, they wouldn’t be able to go to Phase 3, but with that data, you could say that “this dose” should then produce “this level” of huntingtin lowering.

GV: Going straight to Phase 3, how much shorter would the whole program be?

AS: It’s definitely in the years.

FB: Yes, because if they were to do a Phase 2 study first, it would probably take three years to enroll and run. Roche wants to get this drug to patients as quickly as possible, assuming it works. They understand the disease. They understand the need for the patients.

GV: Whether Phase 2 or 3, when would the next study begin?

FB: I would anticipate towards the end of next year.

An important milestone

GV: What is the historical significance of the Ionis breakthrough?

FB: It’s an important milestone for the Huntington’s community. The mutation in the huntingtin gene was described in 1993. This is the first drug to go into clinical trials that is directly on target. It addresses the cause of the disease. We’re extremely excited that we’re actually seeing this basic science and all the work that NIH and other agencies have funded over the last 25 years now being translated into something that could actually have an impact for Huntington’s patients.

This bodes well for other neurological diseases. It has potential to markedly change how we treat those diseases. Perhaps this technology platform [the Ionis gene-silencing approach] would be beneficial for them as well. For patients out there overall, this is extremely important.

(For additional information about next steps in the IONIS-HTT_Rx program, click here for a Q & A with Dr. Ed Wild, an advisor and investigator of the program. You can also read a FAQS from the Huntington's Disease Society of America by clicking here.)

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

(In the video below, watch my report on the December 11 Ionis announcement.)

News from Ionis: drug reduces toxic Huntington's protein, trial may jump straight to Phase 3! from Gene Veritas on Vimeo.

Ionis Phase I Huntington’s disease trial at halfway mark: ‘No surprises so far’ means good news

At its halfway mark, Ionis Pharmaceuticals' historic Huntington’s disease Phase 1 gene-silencing clinical trial is on track to finish as scheduled in late 2017, company officials said in an interview on September 26.

“What we can say is that the trial is going well,” said Frank Bennett, Ph.D., Ionis senior vice president of research and the franchise leader for the company’s neurology programs.

Dr. Bennett added that no “issues” have arisen so far in the Phase 1 safety and tolerability study of its drug IONIS-HTT_Rx in patients with early HD. IONIS-HTT_Rx aims to reduce the production of huntingtin protein in brain cells. This approach, if it advances to Phases 2 and 3, may have the potential to slow, halt or perhaps even reverse the progression of HD symptoms. The trial began in September 2015, with participants in England, Germany, and Canada.

The Ionis HD team explained that the Phase 1 trial is not assessing the drug’s efficacy. Each patient in the trial receives the drug for just three months – not long enough to gauge any impact on symptoms.

Furthermore, the trial is “double-blinded”: trial participants, trial administrators, and Ionis scientists do not know who is getting the drug or a placebo. This insures that bias and other external factors don’t affect the trial results.

Nevertheless, the absence of problems is good news.

No surprises have occurred to date, commented Anne Smith, Ph.D., the Ionis director of clinical development and the individual responsible for the day-to-day management of the trial.

“It’s blissfully quiet,” Dr. Smith said. “You don’t want surprises in clinical trials. Most surprises in safety trials are bad surprises. This one is surprise-free to date.”

Also, trial participants had no difficulties with the delivery of the drug via injections into the spine (so-called intrathecal injections), added Roger Lane, M.D., the Ionis vice president for neurology clinical development and one of the designers of the trial.

Watch my reaction after the interview at Ionis headquarters on September 27 in the video below.

Ionis Phase I HD Trial at Halfway Mark: 'No Surprises So Far' Means Good News from Gene Veritas on Vimeo.

Phase 2 could start in 2018

“We’re continuing to enroll patients in the study,” Dr. Bennett said. A total of 36 patients divided into four cohorts – each subsequent cohort taking a higher dose of IONIS-HTT_Rx – will participate in the trial.

Ed Wild, M.D., Ph.D., one of the administrators of the trial at University College London, announced in June at the annual convention of the Huntington’s Disease Society of America in Baltimore that the third cohort had received permission to receive the drug. (Click here to watch a video of Dr. Wild’s presentation.)

“This is a new therapy, and we want to make sure that we’re doing no harm,” Dr. Bennett emphasized. “Everything is geared towards the safety of the drug at this stage.”

If Phase 1 confirms safety and tolerability, a year-long Phase 2 trial to measure efficacy in a larger number of patients likely would start in 2018, Dr. Bennett said.

Infants on an Ionis SMA drug living longer

The update provided by the Ionis HD team came in the wake of further validation of the company’s scientific approach.

Ionis makes antisense oligonucleotides (ASOs, artificial strands of DNA) that alter the expression of genes and can therefore potentially serve as treatments for genetic diseases. On August 1, Ionis and its partner Biogen actually halted a Phase 3 trial of an Ionis ASO (nusinersen) in infants with spinal muscular atrophy (SMA) because the drug, which increases the level of a key protein, was working so well.

On September 27, Biogen announced that it had completed its application for priority review of nusinersen by the U.S. Food and Drug Administration (FDA).

Like HD, SMA is a genetic neurodegenerative disorder. It primarily affects children, who “end up becoming paralyzed over time,” Dr. Bennett explained, and become vulnerable to respiratory infections or other diseases. Children diagnosed with the most severe form of SMA generally live less than a year, he said. In a less severe form of SMA, children lose the ability to walk over time as they grow up, Dr. Bennett added.

“I think the surprising thing that we found – and this was evidence early in the program – was that we didn’t just stop the decline in these patients, but we actually reversed it,” Dr. Bennett said. “That was really unexpected. I should say that they’re not cured of the disease, but they’re doing much better now than expected. They are surviving longer based on the natural history of the disease.”

These results demonstrated the body’s capacity to mend once the cause of a disorder is removed, he observed.

“We’re hopeful that will also occur in Huntington’s,” Dr. Bennett affirmed. “We have to demonstrate it, but I think there’s a precedent now in these neurodegenerative diseases. If you remove the insult or the toxicity, you can recover function.”

Dr. Frank Bennett of Ionis makes a point during discussion of the company's Phase 1 clinical trial for a Huntington's disease treatment (photo by Kristina Bowyer, Ionis)

Preparing for the HD clinical study

In the Phase 1 IONIS-HTT_Rx trial, clinical trial investigators are collecting some information about the drug’s effect on biomarkers (indicators of a disease mechanism or drug impact) that may help the team design a potential Phase 2.

According to Dr. Lane, before a patient receives each of the four planned doses, the trial administrators collect samples of cerebrospinal fluid (CSF) that will be used to measure levels of huntingtin protein and a variety of other protein markers of neuronal injury and inflammation. Patients also undergo brain scans to look at the volumes of, and the connectivity between, different parts of the brain that are known to be affected in HD.

Another biomarker is neurofilament, described by Dr. Bennett as a protein involved in the cytoskeleton or internal “scaffold” of neurons.  “It’s something very specific to neurons,” said Holly Kordasiewicz, Ph.D., the Ionis director of neuroscience drug discovery, who participated in selecting the ASO, researched it in animals, and is developing biomarker tests for the Phase 1 study. “When the neurons are damaged, neurofilament is released. In a number of neurodegenerative diseases, neurons are dying and neurofilament levels go up.”

In HD, brain cells die. In a clinical study, a decrease in neurofilament would suggest that the drug is protecting neurons, Dr. Kordasiewicz added.

Ionis Huntington's disease clinical trial planners Dr. Anne Smith (left), Dr. Roger Lane, and Dr. Holly Kordasiewicz meet with Gene Veritas (in green shirt) on September 26, 2016, to provide an update on the company's Phase 1 HD trial (photo by Kristina Bowyer of Ionis)

Getting the design of Phase 2 right

The participants in the IONIS-HTT_Rx study undergo a battery of tests that assess memory, thinking, movement, behavior problems, and abilities to perform every-day activities. This is in preparation for use of such measures in a potential Phase 2.

“We’re trying to get the information to design the best efficacy study that we can,” said Dr. Kordasiewicz. “A really sad outcome would be failure of an efficacy study due to the wrong design, not because the drug’s not working. You have to be sure you’re picking the right dose and the right endpoints for the efficacy study.  That’s why all the extra stuff goes into these Phase 1 trials, so that you can get the design right and have the best shot at giving the drug the best chance at working.”

The large burden of work on patients and trial administrators in Phase 1will ultimately allow Ionis (and its partner Roche) to “simplify” potential Phase 2 and 3 trials, making them quicker and making it easier for patients to participate, Dr. Bennett added.

Seeking answers to key questions

This is the first time that an HD gene-silencing drug is going into the human brain. In animals such as mice and non-human primates, the drug gets into both the cortex (the outer, main part of the brain, linked to consciousness) and the striatum (a part of the brain deep under the surface that is involved in movement). Both areas are affected by HD.

A key question for researchers: must IONIS-HTT_Rx reach the striatum to help alleviate HD?

According to Dr. Kordasiewicz, the latest research in HD mice (conducted by William Yang, M.D., Ph.D., of the University of California, Los Angeles) demonstrates that silencing the huntingtin gene in the cortex was more effective than silencing the gene in the striatum, but that silencing in both cortex and striatum was the most effective approach.

Another concern of scientists and HD patients and their families involves the abilities of the ASO, or gene-silencing drug. Should the ASO be designed to reduce only the so-called “bad,”mutant huntingtin? Or is it okay to reduce both the bad and the normal version, which is inherited from the unaffected parent? The IONIS ASO is expected to do the latter.

According to the Ionis HD team, the controversy over this question is diminishing. Studies in animals support the safety of approaches that reduce both mutant and normal huntingtin.  Additionally, Dr. Guohao Wang’s work in mice showed that eliminating huntingtin completely in later life did not have any adverse consequences.

“That was good evidence to support our approach,” said Dr. Lane.

Involving the U.S., thanking patients and families

Many in the HD community have asked: why didn’t Ionis conduct Phase 1 in the United States? And would a potential Phase 2 include Americans?

“I’d be surprised if the U.S. wasn’t involved in a Phase 2 study, as well as additional countries, but I don’t think we are in a position to say specifically which countries are going to be involved,” Dr. Bennett commented. “There were strategic decisions that caused us to go to Europe and Canada first. It’s not that we want to ignore the U.S.” He explained that it was faster to start a trial in Canada and Europe.

The Ionis HD team thanked the Phase 1 participants and their families for their involvement in the Phase 1 study.

“It’s been a very good community and very supportive of our efforts,” said Dr. Bennett. “We also want to thank them for their patience.”

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

(Click on the links below for past coverage of the Ionis HD project.)

Chief Huntington's disease drug hunter: 'every confidence first treatments' in the works

Huntington's disease patients get first dosing in historic Isis Pharmaceuticals' gene-silencing drug trial

Isis Pharmaceuticals launches historic clinical trial to silence Huntington's disease gene

Moving toward a potential treatment: Isis, CHDI researchers outline upcoming Huntington's disease gene-silencing trial

A key new ally in the search for Huntington's disease treatments

Quickening the pace towards a Huntington's disease gene-silencing clinical trial: pharma giant Roche, Isis enter partnership

Designing the best drug possible to defeat Huntington's disease

Building a 'laser-guided missile' to attack Huntington's disease

Observing the cure in progress