Skip Content
Page Banner Image

RG6042 (formerly known as IONIS-HTTrx) Huntingtin-Lowering Trial Information

For more information on this trial click here.

June 2018 Update:

Roche Global HD Community Letter

**While no new information about the study is presented, we learn that Roche is committing to smaller studies as well – an ongoing open label study and a “natural history study” which does not involve active treatment.

June update: Getting to know Roche & Genentech, RG6042 (formerly known as IONIS-HTTRx ) Huntington’s disease development programme

Dear global Huntington’s community,

As many of you are still getting to know us (and vice versa), we would like to take this opportunity to tell you more about our company, philosophy on working with the HD patient community, commitment to collaborate to advance science, and the investigational molecule RG6042 development programme.

Roche & Genentech: one company, two names

Roche is a global biotech company focused on advancing science to improve people’s lives. We were founded 122 years ago in Basel, Switzerland and now have a network of more than 94,000 employees working in 100+ countries. We believe in:

  • Investing in and following the science. We invest more on research and development than any other healthcare company – last year alone over 10 billion Swiss Francs (~$10.5 billion US dollars) – and we’ve translated that science into approved therapies that have fundamentally changed the way numerous conditions such as cancer, haemophilia, and multiple sclerosis are treated.
  • Innovation and focusing on areas of unmet need. We aim to transform how diseases can be treated, and we’ve earned various Health Authorities designations – including 21 breakthrough therapy designations from the US Food and Drug Administration. We certainly hope to transform the way in which HD impacts your families.

Given all the communications about Roche in HD, we want to clarify our company name. Globally and in most parts of the world, you know us as Roche, but in the United States our pharmaceutical division is called Genentech. This is due to the 2009 company integration of Roche and Genentech, a US-based company and the world’s first biotech company. What’s important for you to know is that Genentech = Roche pharmaceuticals in the US, and we are one company working seamlessly together.

Partnering with the Huntington’s disease community

At Roche and Genentech, we are proud of our history of working with patient groups. Our goal is to be a trustworthy partner and for all partnerships to reflect common values of integrity, maintenance of independence, respect, equity, transparency and mutual benefit.

We have dedicated people and teams at both the global- and country-level focused on developing sustainable collaborations with patient communities. Open and constructive dialogue is crucial. This helps you know what can be expected from us, and it helps us better understand how to serve patients, carers and physicians, and to focus our activities on areas that are most beneficial to the communities we serve.

Collaborations in HD to advance scientific progress

Since our partnership with Ionis Pharmaceuticals started five years ago, we have had the privilege of working with leading experts and HD groups to advance the scientific understanding of HD and mutant huntingtin lowering. Collaborations have led to:

  • Design of the first-in-human huntingtin lowering clinical study and follow-on open label extension study,
  • Optimisation of a mutant huntingtin protein (mHTT) assay or measurement test, and
  • Development of clinical and digital endpoints to better understand and measure the impact of HD and disease progression.

Since taking over development of RG6042 from Ionis at the end of 2017, we have and will continue to engage with the community (e.g., patient groups, medical professionals, health authorities, payors, etc.). We commit to incorporating diverse perspectives in the design of the RG6042 development programme, as well as contributing to the advancement of the broader scientific understanding of HD. This is a commitment and journey we share with the HD community.

RG6042 development programme update

The Phase I/IIa study evaluating RG6042 in people with early HD has completed. This is an exciting time for HD, but there is still much work to be done before it can be determined if RG6042 can slow the relentless progression of HD. Big questions exist such as:

  • What are the effects on lowering mHTT over a period of time longer than the 13-week Phase I/IIa study?
  • Do any unexpected safety concerns emerge when we treat a larger group of people for a longer time?
  • Does sustained treatment slow or stop the progression of HD?

We recognize the medical urgency that exists in HD and our team is committed to answering these big questions with other studies in early HD, collaborations with the HD community, and engaging global Health Authorities on the design of a global clinical development programme.

What’s happening next?

We are planning studies that can provide Health Authorities with enough data to assess the benefits and risks of the investigational molecule RG6042, while also balancing speed and efficiency.

  • A longer, larger global study. As previously announced, we are in the planning stages of a global study designed to detect clinical benefit and evaluate longer-term safety in early stage HD. Details about the study, including eligibility criteria, planned start date, and study sites around the world, will be announced as soon as these aspects are finalized.
  • Additional studies. We are also committed to conducting smaller, targeted studies including:
    • The ongoing open-label extension study of RG6042 for those who participated in the Phase I/IIa study. This study looks at the safety and tolerability of longer-term dosing of RG6042, among other measures.
    • A “natural history” study to further understand the role of mHTT and disease progression in the absence of any active treatment. This small study is also in the planning stages and not yet open or enrolling.

We understand that families may wish to seek access to investigational medicines as soon as possible. However, access to RG6042 can only be through clinical trial participation at this time. Because the benefits and risks of RG6042 are not fully understood, we are not able to grant pre-approval, compassionate use or “right-to-try” requests.

With the support of the HD community we are working with urgency and care to develop an appropriate clinical development programme that answers important questions around RG6042. We look forward to providing you with additional updates in September.

Mai-Lise Nguyen, on behalf of the Roche HD team
Patient Partnership Director, Rare Diseases

April 2018 IONIS Update FAQ:

The Huntington Society of Canada (HSC) Answers Questions Regarding the April 24th IONIS-HTTRx Announcement

On April 24th, 2018, Ionis Pharmaceuticals made an announcement about the Phase 1/2 clinical trial of their huntingtin-lowering drug, IONIS-HTTRx (RG6042). The news was shared publicly in a press release and the data was highlighted at the American Academy of Neurology (AAN) Annual Meeting.

What did the press release say?

Mainly, it restated what we already know: the drug is safe, and it lowered levels of huntingtin, the protein that harms brain cells in Huntington disease (HD). The newest information, presented on April 24th, is that overall, participants with lower huntingtin levels also did a bit better on clinical exams that test HD symptoms. However, the study was only designed to be sure of safety, not efficacy, so a larger trial still needs to be conducted.

So are they saying that the drug worked?

It’s not possible to draw that conclusion right now. All we know is that it’s safe and landed on the genetic target it was designed to hit. The clinical findings shared by Ionis are exploratory – the trial only involved 46 participants in total, which is not enough to be sure it could help with symptoms. Even though the overall conclusions are very promising, the statistics have not yet shown a clinical benefit.

What’s next? Does this knowledge change anything going forward?

No. Ionis is passing the torch on to Roche Pharmaceuticals, a larger company that is invested in the HD community. An experienced international team has been assembled and is tasked with the planning and coordination of a global Phase 3 clinical trial. You can read their most recent message to the community here. In the meantime, we’re encouraged that the analysis of the Phase 1/2 data continues to show promising results. We’re also really excited that these results are being given the spotlight at international research conferences. This will positively impact families by raising awareness of HD among medical professionals worldwide.

If it’s so promising, what’s the holdup?

Ensuring that drugs are safe and effective is a time-consuming and heavily regulated process. Roche has a lot of work to do, including designing the trial with care, identifying the medical teams and facilities that will take part, making sure that professionals are equipped and trained to administer the drug, producing the drug itself, and sorting out funding and regulations at different agencies worldwide. All of these steps require planning, paperwork, and patience. Rest assured that there are smart and compassionate minds involved, including patients and families with HD, working to bring this drug to the clinic as quickly as possible.

Can I sign up to be in the trial, or put my name on a list?

Unfortunately, no. The way that clinical trials usually recruit is through existing doctor-patient relationships, where the doctor decides if a patient might be eligible, and makes a referral. That’s one reason why HSC encourages people to see an HD expert at an HD or Movement Disorders clinics with a research interest, and to join Enroll-HD where available.

There’s been an outpouring of folks who are ready to take a big leap and participate. The trial is not at that stage yet, and HSC is not in control of any aspect of the design, participation, or eligibility. There will be fewer “spots” than willing participants, which will understandably lead to some disappointment. We do not encourage people to consider a big life shift (like moving) based on their desire to participate in a trial.

However, we are thrilled about the community’s engagement and we’ll continue to provide and interpret any new information we hear. There may be other research opportunities near you, as well – check out  for details.

What is HSC doing to support the trial and the community?

HSC staff are working very closely with members of the Roche team to ensure timely and proper information about this trial will be shared with the community as soon as it becomes available. HSC is also a founding member of the Huntington Disease Coalition for Patient Engagement (HD-COPE), which helps industry access input from patients and families. HD-COPE will help companies like Roche make sure that trial planning, measurements, and participation requirements seem reasonable to the real experts – people with HD and their loved ones.

Finally, we continue to provide trial details and contact information for participating in open research studies on The upcoming Roche trial has not yet begun, and is not yet listed there.

When do you think this drug will be available?

That’s extremely difficult to answer. Trials can take several years, and a lot of care must be taken with this one, because it’s so important and so different from drugs that address just the symptoms of HD. We’d love to be able to say there’s a definite timeline, but this is uncharted territory and we simply don’t know. The first step is to see whether it can improve symptoms or slow down HD, and that’s the focus of the Phase 3 trial.

What can I do right now?

Make sure you’re under regular care with a doctor or team who has experience with HD, particularly one with a research interest. Follow the news at HDBuzz, on our regular HSC website updates or on HSC’s social media pages. Check out  for research and trial opportunities. Above all, take care of yourself and those around you! In the fight against HD, family is everything.

Edited for Canadian content on 4/26/2018

Thank you to the HDSA for sharing their document: The Huntington’s Disease Society of America Answers Questions Regarding the April 24th IONIS-HTTrx Announcement.

April 24, 2018 Update:

On April 24, Dr. Sarah Tabrizi, the lead investigator in the Ionis trial, presented findings at the American Neurology Association (ANA) meeting.  Much of the information presented was not new and you can read more about the findings from the Phase 1/2a study here.

One bit of new data presented showed an interesting relationship between the amount of Huntingtin-lowering and the change in the patient’s clinical HD scores.  Please see the thread below from HDBuzz’s Twitter feed.

We think it is important to provide the following additional information:

  1. No statistically significant group-wise clinical HD improvements were measured. Phase 1/2a of the HTTRx trial was not large enough, run long enough or designed to make this determination.
  2. What we do know is that initially the therapy was well tolerated, is initially safe, and reduced the huntingtin protein.
  3. The open label extension (which has started) along with the next phase of the trial (which will be larger and longer) should tell us whether or not the HTTRx drug has a positive clinical impact on an individual’s HD symptoms.

Click here to read the IONIS press release.

Roche is in the planning stages for a comprehensive global study designed to detect a clinical benefit and to evaluate the longer-term safety of the drug.  As we move through 2018 we will have more information as to when the next phase will begin and the sites where the trial will take place.

We are all encouraged by the clinical trials that are addressing the root cause of HD and we will continue to keep you updated as we move forward.

Bev Heim-Myers

CEO, Huntington Society of Canada



April 20, 2018 Update:

Community Statement from Roche Pharmaceuticals

Dear global Huntington’s disease community,

Next week will be another milestone for the development program of the investigational medicine RG6042 (formerly known as IONIS-HTTRx ). On 24 April 2018 results from the RG6042 Phase I/IIa study in Huntington’s disease (HD) will be featured on the main stage of the American Academy of Neurology (AAN) annual meeting, the world’s largest forum for neurology research, which is attended by over 12,000 professionals from around the globe.

We wanted you to be aware that news coverage about this study may occur over the next days. Out of more than 3,000 scientific submissions to AAN, the RG6042 Phase I/IIa study results is one of four presentations selected to be part of the meeting’s top-featured session. HD will receive a spotlight in the neurology community next week, and we would like to give special acknowledgements to (as Dr. Sarah Tabrizi said during her presentation at the CHDI conference) the “true research heroes”- the 46 participants of the Phase I/IIa study. These incredible individuals and their families had the bravery and commitment to join this first-in-human study and advance scientific progress.

We are honored to work with trial investigators and Ionis Pharmaceuticals to share results of the world’s first drug study designed to reduce huntingtin protein at such prominent scientific forums as AAN and last month’s CHDI conference, where the data were first debuted. It is a testament to the broad interest in HD and the increasing hope for effective treatments. More importantly, it is a testament to the collaboration and support of the HD community.

What’s happened?

  • The Phase I/IIa study will be presented on 24 April at the AAN annual meeting. Overall results are
    similar to those previously announced at the CHDI conference.

    • This was a 13-week, first-in-human study evaluating safety and tolerability, where 46 participants received four doses every 28 days.
    • The study showed RG6042 was safe and well-tolerated at all doses.
    • The study was not designed, or expected, to show an effect on clinical symptoms.
    • Exploratory analyses showed that RG6042 lowered levels of mutant huntingtin protein, the protein that causes Huntington’s disease, in a dose-dependent manner.
  • Based on the encouraging signals observed in this study, the development of RG6042 continues. Further research will focus on determining if RG6042 provides a meaningful clinical benefit and if lowering the mutant protein changes the course of HD.

This is an exciting time for HD, but there is still much work to be done. More research and larger studies are needed to determine if RG6042 can slow the relentless progression of HD.

Important notes/what’s happening next:

  • Our team and collaborators continue to analyze the Phase I/IIa data and exploratory signals.
  • The Phase I/IIa data will continue to be presented at upcoming scientific and community forums around the world, and they will be submitted for peer-reviewed scientific publication. Ensuring ongoing communications with the scientific community is part of Roche’s commitment to data sharing, which enables education, discussion and other researchers to more easily build on insights and expand scientific progress.
  • An open-label extension study of RG6042 has started for those who participated in the Phase I/IIa study. This study looks at the safety and tolerability of longer-term dosing of RG6042, as well as the effects on mutant huntingtin protein and other measures tested in the Phase I/IIa study.
  • We are in the planning stages of a comprehensive clinical development program for RG6042, including a global study designed to detect clinical benefit and evaluate longer-term safety.
    • We are collaborating with the HD community and engaging global Health Authorities on the design of the clinical development program.
    • We will share details about study information, including eligibility criteria, planned start date, and study sites around the world, as soon as these aspects are finalized.
  • At this time, because the benefits and risks of RG6042 are not fully understood, we are not able to grant pre-approval or compassionate access.

Roche’s drive to develop treatments for HD is inspired by you – the people whose lives are affected by this disease. We are grateful to the HD community for its ongoing engagement in clinical studies to further the progress in HD research. Please know that we are working with urgency and care, and in partnership with the HD community, to develop a comprehensive clinical  development program. We look forward to providing you future updates.

Your Roche HD Team



March 1, 2018 Update

Today Ionis released positive top-line data from their completed Phase 1/2 study of IONIS-HTTRx in people with early stage Huntington disease at the 13th Annual CHDI HD conference. The data demonstrates that the IONIS-HTTRx drug has successfully lowered the harmful huntingtin protein in cerebral spinal fluid, the drug is safe and well tolerated. This data is promising and gives us substantive hope that a treatment is near.


What happened?

  • Today, March 1, 2018, Ionis Pharmaceuticals released positive top-line data from their completed Phase 1/2a study of IONIS-HTTRx in people with early stage Huntington disease at the 13th Annual CHDI HD conference.
  • This is a follow-up to the announcement on December 11, 2017, where Ionis Pharmaceuticals released the preliminary results of a global Phase 1/2a clinical trial that tested IONIS-HTTRx.
  • This therapy is designed to target the root cause of HD.
  • This Phase 1/2a trial took place in Canada and Europe. It was a small trial, with about 46 participants.

What were the results?

  • The therapy was well tolerated and there were no safety issues.
  • Reductions in the toxic mutant huntingtin protein were observed in the study participants.
  • This is promising news. The therapy is designed to lower the mutant huntingtin.  From the press release it seems like huntingtin lowering has been achieved.

Important Notes:

  • This study was short. Each patient only received 4 months of injections.  This is not enough time to look for changes in the rate of HD progression.
  • At this point, we do not know if this drug made peoples’ HD symptoms better.

What is next?

  • Roche Pharmaceuticals is taking this trial forward.  The next step for this program will be to continue the trial to later stages with more participants. Researchers will investigate if reductions in the mutant huntingtin protein benefit people with Huntington disease by favourably impacting HD symptoms.
  • Our expectation is that the next phase of this trial will start in late 2018 or early 2019.
  • This will be a global trial. The trial sites have not been confirmed yet, but our hope is that more sites will be offered in Canada.

The Canadian HD Community has been leading the charge. Canadians are a part of this clinical trial helping us all to get to this important point.  There is still much to do and learn.  On our website you will find the complete press release and the community statement from Ionis and Roche Pharmaceuticals.  You will also find the community statement from Ionis and Roche below.

We are so thankful to all of the brave volunteers who signed up and committed to this trial.  This is a very promising day for the HD community and sets us up for an exciting 2018.  For our family members, if you have specific questions about participation in clinical trials, we recommend that you speak with your clinician.  As more information is made available, we will continue to update you.

Warm Regards,

Bev Heim Myers



CEO, Huntington Society of Canada

IONIS-Roche CHDI HD Community Statement



March 1, 2018

Dear members of the Huntington’s community,

On March 1, 2018, Ionis Pharmaceuticals, Inc. and Roche presented initial results from the completed Phase 1/2a study of IONIS-HTTRx (now known as “RG6042”) in people with Huntington’s disease (HD) at the 13th Annual CHDI HD Therapeutics conference. The study was a 13-week, randomized, placebo-controlled, dose escalation study in 46 participants with early stage HD. The study evaluated IONIS-HTTRx (RG6042) at five different doses, given monthly, for a total of four doses. We are excited to provide you with a summary of information from the completed study.

  • In the Phase 1/2a study, the mutant huntingtin protein (mHTT), which causes HD, was substantially reduced in a dose-dependent manner in participants treated with IONIS-HTTRx (RG6042).
  • Participants who received either of the two highest doses of IONIS-HTTRx (RG6042) (90 mg or 120 mg) experienced a reduction of mHTT levels in their cerebral spinal fluid (CSF) that were, on
    average, approximately 40% lower than at the start of the study, with some individuals experiencing a lowering as high as 60%. At the last measurement, the levels of mHTT were continuing to decline in most IONIS-HTTRx (RG6042)-treated participants, suggesting that larger reductions may be possible with continued dosing.
  • This magnitude of reduction of mHTT in CSF is within the range predicted to provide clinical
    benefit, based on available evidence of what was needed for improvement in animal models of HD.

The purpose of the Phase 1/2a study was to determine safety and tolerability of IONIS-HTTRx (RG6042). This study was not designed to detect an effect on clinical symptoms. We are pleased that the study showed IONIS-HTTRx (RG6042) was safe and well-tolerated at all doses and lowered CSF mHTT levels in a dosedependent manner, and therefore supports continued development. Since mid-December 2017, Roche is leading the future studies and development of this investigational medicine, which was renamed RG6042.

Recent progress:

  • An open-label extension study of IONIS-HTTRx (RG6042) has started for those who participated in the recently completed Ph1/2a study. This study looks at the safety and tolerability of longer-term dosing of IONIS-HTTRx (RG6042).
  • The next step is to conduct a larger study designed to detect clinical benefit and evaluate longer-term safety. In this study it will determine whether the lowering of mHTT, observed in the first study of IONIS-HTTRx (RG6042), translates into meaningful benefit for people living with HD.
  • Roche is collaborating with the HD community and engaging global health authorities on the design of this larger study. Roche will share details about this planned study, including eligibility criteria, planned start date, and study sites around the world, as soon as these aspects are finalized.

This study will answer critical questions for regulatory approval and broad access. At this time, because the benefits and risks of IONIS-HTTRx (RG6042) are not fully understood, we are not able to grant pre-approval or compassionate access.

In summary, we are very encouraged by the promise of IONIS-HTTRx (RG6042) and look forward to
continuing to partner with the HD community. We recognize the urgent need to bring effective therapies to individuals affected by HD, and our teams are working to advance IONIS-HTTRx (RG6042) into the next clinical study as quickly as possible.


Your Roche & Ionis Team

Click here to read the original statement.

We support those facing huntington disease
 Latest Blog


Let Us Know How We Can Help
Enter your name, email address and question(s) below for assistance.



Stay in Touch!
Enter your email address below to receive occasional updates.

Newsletter Sign-up