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RG6042 Huntingtin-Lowering Trial History

March 22, 2019 – Changes to Roche’s Generatin HD1 Study Design

Roche Pharmaceuticals sent a letter to the global HD community to provide an update on the design of the GENERATION HD1 study.  You can read the full letter from Roche here.  HDBuzz has also published an article on the study design change.  You can find that article here.

Key changes to the GENERATION HD1 study

The study arms involving treatment every two months and placebo will remain the same. The study arm that tests monthly treatment of RG6042 will be replaced with one that tests a less frequent dose of once every four months (every 16 weeks).

All patients will undergo lumbar puncture procedures every two months and are randomised to one of the study arms below:

  • Study arm 1: RG6042 every two months (no placebo)
  • Study arm 2: RG6042 every four months (placebo during alternating procedures)
  • Study arm 3: Placebo every two months

Roche made this change after a review of the nine-month open-label extension data that supported the exploration of less frequent dosing.

We believe that this is positive news for the HD community as the design changes will make study participation less demanding for patients, their families, and healthcare providers.  For the individuals that have already started the GENERATION HD1 study, you will have the option to move to the open-label extension study.  Roche also informed us in their letter that there will be a brief pause in recruitment while the new study design is approved.

For our family members, if you have specific questions about these changes or participation in clinical trials we recommend that you contact your local neurologist, Movement Disorders or Huntington disease clinic.  We will continue to stay in touch and keep you updated.

Robin Markowitz
CEO, Huntington Society of Canada

January 28, 2019– Roche announces that the first patients have been enrolled in the HD Natural History and Phase III GENERATION HD1 clinical studies

Today, Roche Pharmaceuticals sent a letter to the global HD community to provide an update on the progress of their HD clinical trials. You can read the full letter from Roche here.

We have also included the FAQ from Roche below.

  • HD Natural History Study
    • This observational study for early manifest HD will run in the USA, Canada, Germany and the UK; planned study sites were announced in late 2018.
    • Initial sites have opened and the first patients have enrolled; the Roche team continues to work to open recruitment at all study sites as quickly as possible.
    • In Canada the HD Natural History Study will take place in:
      • Vancouver, British Columbia at the University of British Columbia Centre for Huntington disease
      • Toronto, Ontario at the Centre for Movement Disorders
  • Phase III GENERATION HD1 Study
    • Roche has received health authority approvals in the USA and Canada to start this pivotal study for manifest HD.
    • Planned study sites for those countries were announced at the end of 2018 and the first patient has now enrolled.
    • This study will run in approximately 15 countries; Roche is diligently working to set up study infrastructure and receive approvals in the remaining countries.
    • In Canada, the expected GENERATION HD1 study sites are:
      • Vancouver, British Columbia at the University of British Columbia Centre for Huntington disease
      • Edmonton, Alberta at the University of Alberta
      • Toronto, Ontario at the Centre for Movement Disorders
      • Ottawa, Ontario at the Ottawa Hospital
      • Montreal, Quebec at the Centre Hospitalier de l’Université de Montréal
      • Halifax, Nova Scotia at True North Clinical Research

Up-to-date information about these trials as well as additional HD clinical trials can be found on our website at www.huntingtonsociety.ca/hd-clinical-trials.

We applaud the volunteers who have stepped up and continue to step up to advance research. Their bravery pushes us closer to meaningful treatments. We have many reasons to be hopeful.  This update from Roche is another positive step forward.

For our family members, if you have specific questions about participation in clinical trials we recommend that you contact your local neurologist, Movement Disorders or Huntington Disease Clinic.  We will continue to stay in touch and keep you updated.

Robin Markowitz

CEO, Huntington Society of Canada

Frequently asked questions and answers from Roche

What is the HD Natural History study?

This 15-month observational study aims to further understand the role of mutant huntingtin protein in disease progression, including how levels of mHTT change over time in the absence of any drug treatment. There is no drug treatment in this study. This study will include up to 100 participants with early manifest (Stage I and II) HD. For all patients who complete the HD Natural History study, an open-label extension study with the option of receiving RG6042 (no placebo control) is planned, pending eligibility, approval by Authorities and Ethics Committees/Institutional Review Boards and if data support the continued development of RG6042.

The HD Natural History Study will run at up to 17 sites in Canada, Germany, the United Kingdom and the United States. For more information about the study/trial sites in Canada visit www.huntingtonsociety.ca/hd-clinical-trials or contact the local Roche Medical Information team: Canada: 1-888-662-6728

What is the Phase III GENERATION HD1 study?

The GENERATION HD1 study will evaluate the efficacy and safety of RG6042 treatment for manifest HD. The study will run over a period of 25 months (approx. two years). GENERATION HD1 is designed to determine whether RG6042 is safe and effective, and therefore includes a comparison to placebo. Participants will be randomised to one of three treatment study arms: RG6042 monthly, RG6042 once every two months (bi-monthly) or placebo monthly. This means for every two participants randomised to RG6042, one will receive placebo. The study is “double-blinded,” meaning neither the participant nor his/her investigator or site staff will know which study arm the participant is assigned.

For all patients who complete the GENERATION HD1 study, an open-label extension study with the option of receiving RG6042 (no placebo control) is planned, pending eligibility, approval by Authorities and Ethics Committees/Institutional Review Boards and if data support the continued development of RG6042.

The GENERATION HD1 study will enroll up to 660 patients with manifest HD at 80-90 sites in approximately 15 countries around the world. Planned sites have been announced for Canada and the United States of America.

For more information about the study/trial sites visit www.huntingtonsociety.ca/hd-clinical-trials or contact our Clinical Trial Information Support Line 1-888-662-6728. Information about additional countries/sites involved in the study will be announced, as those details are finalised.

How are the clinical study sites selected?

A variety of factors influence site selection, including assessments on experience with HD studies, clinic infrastructure capacity to run the study as well as usual site activities, ability to operationalise the study as quickly and completely as possible, patient population, and geographic location.

What if there is not a study site near where I live? Can I relocate to participate in a study?

Clinical studies are subject to international, national and local laws and regulations. Additionally, factors such as institutional site policies, health insurance and travel burden may impact your ability to relocate and be accepted into one of the study sites. Eligibility and enrolment are decided by the study investigator at each site, who takes into account all these factors and may also wish to speak to you or your local HD specialist for more information. Whether your HD centre is selected for participation or not, this is no reflection on the quality of the many outstanding HD clinics and dedicated care providers around the world. The need in HD is greater than the capacity of our development programme. We have designed the programme to provide the required data to health authorities so that the benefits and risks of RG6042 can be determined as quickly as possible. Our ultimate goal is that this investigational medicine can be approved by health authorities, and made accessible to the broader HD community.

Can I access RG6042 outside of clinical studies?

Currently, access to RG6042 is only through clinical study participation because the benefits and risks of RG6042 are not yet fully understood. This means that we are not able to grant pre-approval, compassionate use or “right-to-try” requests at this time. As our understanding of the benefits and risks of RG6042 grows, we will regularly evaluate this position.

Your clinical studies are in early manifest and manifest HD. Will you study RG6042 in other patient populations (e.g., juvenile onset HD or prodromal HD)?

We recognise the critical medical need for a treatment for HD, especially for people living with severe forms like juvenile onset HD. Once there is sufficient scientific and safety rationale, our team will consult with HD community experts and explore the potential use of RG6042 in populations beyond manifest HD.

 

 


DECEMBER 2018 PHASE III GENERATION HD1 STUDY UPDATE:

On December 19, 2018, Roche Pharmaceuticals announced the expected locations of the clinical trial sites in Canada that will be participating in the Phase III GENERATION HD1 study.

The locations of the Canadian sites that are expected to participate in the GENERATION HD1 study are:

  • Edmonton, Alberta – University of Alberta
  • Vancouver, British Columbia – University of British Columbia
  • Ottawa, Ontario – Ottawa Hospital
  • Toronto, Ontario – Centre for Movement Disorders
  • Halifax, Nova Scotia – True North Clinical Research
  • Montreal, Quebec – Centre Hospitalier de l’Université de Montréal

For our families, if you have specific questions about participating in clinical trials we recommend that you contact your local Movement Disorders or Huntington disease clinic.  We will also continue to update the HSC website with the most current information. You can find that information here.

Below is the information regarding the Phase III GENERATION HD1 Study:

  • The GENERATION HD1 study will evaluate the efficacy and safety of RG6042 treatment given once per month or once every two months (bi-monthly) over a period of 25 months (approx. two years).
  • This global study will enroll up to 660 patients with manifest HD at 80-90 sites in approximately 15 countries around the world. The study will start to enroll patients in early 2019.
  • Participants will be randomized to one of three treatment study arms: monthly, bi-monthly or placebo monthly. This means for every two participants randomized to RG6042, one will receive placebo.
  • The study is designed to test the potential effects of RG6042 compared to placebo.
  • The study is “double-blind” meaning neither the participant nor his/her investigator or site staff will know which study arm the participant is assigned.
  • For all patients who complete the GENERATION HD1 study, an open-label extension study with the option of receiving RG6042 (no placebo control) is planned, pending eligibility, approval by Authorities and Ethics Committees/Institutional Review Boards and if data support the continued development of RG6042

At the 2018 HSC National Conference, Dr. Blair Leavitt from UBC and Dr. Lauren Boak from Roche, provided an update on huntingtin-lowering therapies and Roche’s Huntington disease program.  You can view that update on the HSC Facebook page here.

OBSERVATIONAL HD NATURAL HISTORY STUDY:

In addition to the GENERATION HD1 study, Roche Pharmaceuticals also announced locations for their observational study in November.

Below is the information for Roche’s second Huntington disease clinical trial:

  • This 15-month observational study aims to further understand the role of mutant huntingtin in disease progression.
  • There is no drug treatment in this study, as the goal is to understand the natural progression of HD.
  • This study will include up to 100 participants globally with early manifest (Stage I and II) HD at up to 17 sites
  • The sites include Canada, Germany, the United Kingdom and the United States.
  • This study is being run in Canada in:
    • Vancouver, British Columbia – University of British Columbia Centre for Huntington disease
    • Toronto, Ontario – Centre for Movement Disorders

This is a hopeful time for the Huntington disease community and this announcement is another positive step forward.  We will continue to update you as more information becomes available.

Sincerely,

Robin Markowitz

CEO, Huntington Society of Canada


November 2018 Observational Huntington disease Natural History Study Update:

On November 7, 2018, Roche Pharmaceuticals announced the locations of the clinical trial sites in Canada that will be participating in the Observational Huntington disease Natural History Study.

The locations of the Canadian sites participating in the Natural History Study are:

  • Vancouver, British Columbia – University of British Columbia Centre for Huntington disease
  • Toronto, Ontario – Centre for Movement Disorders

These sites are not fully active yet, but Roche hopes to complete the final steps as quickly as possible.  For our families, if you have specific questions about participating in clinical trials we recommend that you contact your local Movement Disorders or Huntington disease clinic.  We will also continue to update the HSC website with the most current information.  You can find that information here.

Below is the information regarding the Observational HD Natural History Study:

  • This 15-month observational study aims to further understand the role of mutant huntingtin in disease progression.
  • There is no drug treatment in this study, as the goal is to understand the natural progression of HD.
  • This study will include up to 100 participants globally with early manifest (Stage I and II) HD at up to 17 sites
  • The sites include Canada, Germany, the United Kingdom and the United States.
  • This study is expected to start enrollment shortly

In addition to the Observational Huntington disease Natural History Study, Roche Pharmaceuticals is also working on the set-up of a second clinical trial that they hope to launch by the end of 2018 or early 2019.

Below is the information for Roche’s second Huntington disease clinical trial.

Upcoming Phase III Generation HD1 study:

  • This global study will enroll up to 660 patients with manifest HD at 80-90 sites in approximately 15 countries around the world. The study is expected to begin at the end of 2018 with patients starting to enroll by early 2019.
  • Participants will be randomized to one of three treatment study arms: monthly, bi-monthly or placebo monthly. This means for every two participants randomized to RG6042, one will receive placebo.
  • The study is designed to test the potential effects of RG6042 compared to placebo.
  • The study is “double-blind” meaning neither the participant nor his/her investigator or site staff will know which study arm the participant is assigned.

At the 2018 HSC National Conference last week, Dr. Blair Leavitt from UBC and Dr. Lauren Boak from Roche, provided an update on Huntingtin-Lowering therapies and Roche’s Huntington disease program.  You can view that update on the HSC Facebook page here.

This is a hopeful time for the Huntington disease community and this announcement is another positive step forward.  We will continue to update you as more information becomes available.

Sincerely,

Robin Markowitz

CEO, Huntington Society of Canada


September 2018 Update:

On September 16, 2018 at the European Huntington Disease Network conference, Roche presented an update on the development of the Huntingtin lowering therapy RG6042 and provided information on two clinical trials that they plan to start by the end of 2018.  You can read Roche’s full letter to the HD community below.

As you may recall, the initial Phase I/IIa trial has completed.  That study demonstrated that the drug was initially safe and that higher doses reduced the huntingtin protein by 40 to 60 per cent.

The next step is to run a trial that answers several key questions: What are the effects of lowering huntingtin over a longer period of time? Do any unexpected safety concerns emerge? And, of course, does sustained treatment slow or stop the progression of HD?

Roche shared more information about the next steps in the drugs development with the announcement of two upcoming clinical trials:

  • Observational HD Natural History Study:
    • This 15-month observational study aims to further understand the role of mutant huntingtin in disease progression.
    • There is no drug treatment in this study, as the goal is to understand the natural progression of HD.
    • This study will include up to 100 participants with early manifest (Stage I and II) HD at up to 17 sites
    • The sites include Canada, Germany, the United Kingdom and the United States.
    • This study is expected to start towards the end of 2018.
  • Phase III Generation HD1 study
    • This global study will enroll up to 660 patients with manifest HD at 80-90 sites in approximately 15 countries around the world. The study is expected to begin at the end of 2018 with patients starting to enroll by early 2019.
    • Participants will be randomized to one of three treatment study arms: monthly, bi-monthly or placebo monthly. This means for every two participants randomized to RG6042, one will receive placebo.
    • The study is designed to test the potential effects of RG6042 compared to placebo.
    • The study is “double-blind” meaning neither the participant nor his/her investigator or site staff will know which study arm the participant is assigned.

What is next?

Site and study information will be shared by Roche on a progressive basis. Once site information is available we will publish it on the HSC website here and share it the community via email, social media and the HSC website.

This is an exciting time in HD research.  Canadians have been instrumental in helping the global HD community to this point.  As we move forward there is still so much to do, and to learn, and Canadians will be part of this important work.

For our family members, if you have specific questions about participation in clinical trials we recommend that you contact your local neurologist, Movement Disorders or Huntington disease clinic.

 

Robin Markowitz

CEO, Huntington Society of Canada

Roche Global HD Community Letter

Dear Global Huntington’s Community,

Thank you for your ongoing support and interest in the investigational medicine RG6042 for Huntington’s disease (HD).

Over the past months we and our partner Ionis Pharmaceuticals have been heavily engaged with communities around the world (patient groups, medical professionals, Health Authorities and payers) to collaborate and build the RG6042 global development programme and upcoming studies. We are eager for RG6042 to advance into further clinical development. In addition, as announced last month, the European Medicines Agency granted RG6042 PRIME (“PRIority MEdicine”) designation, which provides promising medicines enhanced interactions with the agency and the potential for accelerated evaluation.

Next steps for the global RG6042 development programme

Following the completion of the Phase I/IIa first-in-human study of RG6042 in December, there are several important questions that still need to be answered before this investigational medicine can potentially be approved by Health Authorities in countries around the world:

  • What are the effects on lowering mutant huntingtin (mHTT), the toxic protein believed to cause HD, over a period of time longer than the 13-week Phase I/IIa study?
  • Does sustained treatment with RG6042 slow or stop the progression of HD?
  • Do any safety concerns emerge when RG6042 is given to a larger group of people, and for a longer time, than the 46 individuals in the Phase I/IIa?
  • Could a less frequent dose than the monthly dose used in the Phase I/IIa study be effective?

Our upcoming studies have been designed to answer these questions as quickly and as robustly as possible, whilst considering the number of people exposed to an investigational medicine or placebo.

Update on ongoing and upcoming clinical studies

All 46 participants who took part in the Phase I/IIa study are continuing to receive RG6042 as part of an ‘open-label extension’ study run by Ionis. This study assesses the safety and tolerability of longer- term dosing of RG6042 and is being conducted at the nine sites involved in the Phase I/IIa study in Canada, Germany and the United Kingdom.

Two additional clinical studies, run by Roche, are planned to start by the end of 2018. Information about these studies was presented today to the HD community during the European Huntington’s Disease Network Plenary Meeting in Vienna, Austria.

  • The HD Natural History Study: This 15-month observational study aims to further understand the role of mHTT in disease progression. There is no drug treatment in this study, as the goal is to understand the natural progression of HD. This study will include up to 100 participants with early manifest (Stage I and II) HD at up to 17 sites in Canada, Germany, the United Kingdom and the United States. This study is expected to start towards the end of 2018.
  • GENERATION HD1: This will be the world’s first Phase III study testing a molecule designed to lower huntingtin protein. The study design will be submitted to Health Authorities and Ethics Committees/Institutional Review Boards (IRBs) this year. The GENERATION HD1 study will evaluate the efficacy and safety of RG6042 treatment given once per month or once every two months (bi-monthly) over a period of 25 months (approx. two years).
  • This global study will enrol up to 660 patients with manifest HD at 80-90 sites in approximately 15 countries around the world. The study is expected to begin at the end of 2018 with patients starting to enrol by early 2019.
  • Participants will be randomised to one of three treatment study arms: RG6042 monthly, RG6042 bi-monthly or placebo monthly. This means for every two participants randomised to RG6042, one will receive placebo. The study is designed to test the potential effects of RG6042 compared to placebo, whilst limiting the number of people who will be given placebo.
  • The study is “double-blinded,” meaning neither the participant nor his/her investigator or site staff will know which study arm the participant is assigned.
  • Future open-label extension study for all patients who complete the HD Natural History and GENERATION HD1 studies: If approved by Authorities and Ethics Committees/IRBs, and if data support the continued development of RG6042, we plan to offer an open-label extension study that would provide the option of receiving RG6042 (no placebo control) to all patients who complete these studies.

Our team is working with urgency to start the HD Natural History and GENERATION HD1 studies and we understand that you are eager for more detailed information, such as specific sites, countries and dates.

Study site/country information will be shared on a progressive basis. Once a site is nearly ready to enrol patients, we will update the information on clinicaltrials.gov and on North America’s HDTrialFinder.org. On the next pages of this letter you’ll find additional study information and frequently asked questions and answers about these new studies.

The urgency in which families are seeking a medicine that can slow or stop the progression of HD is deeply felt and shared by our team. Because the need in HD is greater than the capacity of our development programme, we recognise that not every person, nor every capable HD clinic or centre, interested in participating in these clinical studies will be able to participate. Please understand the studies are designed to provide Authorities with the required data so that the benefit-risk of RG6042 can be determined as quickly as possible.

Our team is committed to addressing the scientific questions and promptly completing the RG6042 studies with appropriate rigour. The ultimate goal is that this investigational medicine can be approved by Health Authorities, and made accessible to the broader HD community – a goal that we share with you, the global HD community.

We look forward to providing you updates later this year, and we thank you for your continued partnership.

Sincerely,

Mai-Lise Nguyen, on behalf of the Roche HD team Patient Partnership Director, Rare DiseasesRoche Pharma Research & Early Development / Roche Innovation Centre Basel, Switzerland

Below is an overview about the upcoming studies. Further details about the studies will be posted on clinicaltrials.gov and on North America’s HDTrialFinder.org as information is finalised.

Frequently asked questions and answers

What happens next?

Our team is working with urgency to complete setup of the upcoming clinical studies. This includes obtaining appropriate approvals (from Health Authorities and Ethics Committees/IRBs for each site), training sites, providing materials and resources for study procedures, and importantly ensuring high quality and supply of study drug. We will continue to provide updates as the setup process continues for the HD Natural History and GENERATION HD1 studies. Details about the studies will be posted on clinicaltrials.gov and on North America’s HDTrialFinder.org as information is finalised.

What does “early manifest HD” and “manifest HD” mean?

Someone with early manifest HD is described as someone for which motor (movement) symptoms have presented, but the person is living at home, is able to take care of him/herself and is generally able to work; this is described as Stage I/II HD, according to the Total Functional Capacity (TFC) Scale, a commonly used clinical measure in HD research.

Manifest HD is a broader term, which also includes moderate to some more advanced stages of HD. These individuals are able to live at home, but may also have minor difficulties with activities of daily living; this generally corresponds to Stages I, II and some of Stage III, according to the TFC Scale.

How can I tell if I am/a loved one is eligible for participation in one of the clinical studies? 

The observational HD Natural History Study will enrol people with early manifest HD between the ages of 25-65, and who fulfil additional eligibility criteria. The planned Phase III GENERATION HD1 study will enrol people with manifest HD between the ages of 25-65, and who fulfil additional eligibility criteria. Individuals interested in the GENERATION HD1 study should also feel capable of undertaking a comprehensive, 25-months long study and have the support of his/her HD specialist and site investigator. Further details of studies, including inclusion and exclusion criteria, will be posted on clinicaltrials.gov and on North America’s HDTrialFinder.org, as well as shared with HD healthcare professionals.

We encourage you to speak to your/your loved one’s HD specialist about what may be best for your situation. Your HD specialist can also contact Roche Medical Information in your local country for more information.

Why are you doing an observational natural history study?

The HD Natural History study will further the understanding of the role of mHTT in natural disease progression, including how levels of mHTT change over time in the absence of any drug treatment. This study will enrol patients with a similar profile, e.g., CAG repeat length and age, as those who are participating in the ongoing open-label extension study.

How are the clinical study sites selected?

A variety of factors influence site selection, including assessments on experience with HD studies, clinic infrastructure capacity to run the study as well as usual site activities, ability to operationalise the study as quickly and completely as possible, patient population, and geographic location.

Whether your HD clinic or centre is selected for participation or not, this is no reflection on the quality of the many outstanding HD clinics and dedicated care providers around the world. The need in HD is greater than the capacity of our development programme. We have designed the programme to provide the required data to Authorities so that the benefit-risk of RG6042 can be determined as quickly as possible. Our ultimate goal is that this investigational medicine can be approved by Health Authorities, and made accessible to the broader HD community.

Can you provide a list of expected clinical study sites?

Study sites will be announced on a progressive basis – for example, once a site’s infrastructure and approvals (from Health Authorities and Ethics Committees/IRBs) are in place, and sites are nearly ready to enrol patients. For any clinical study, it is possible that an expected study site does not proceed to enrol participants. This can be for various reasons and we do not want to raise hopes or expectations.

What if there is not a study site near where I live? Can I relocate to participate in a study?

Clinical studies are subject to international, national and local laws and regulations. Additionally, factors such as institutional site policies, health insurance and travel burden may impact your ability to relocate and be accepted into one of the study sites. Eligibility and enrolment are decided by the study investigator at each site, who takes into account all these factors and may also wish to speak to you or your local HD specialist for more information.

Whether your HD clinic or centre is selected for participation or not, this is no reflection on the quality of the many outstanding HD clinics and dedicated care providers around the world. The need in HD is greater than the capacity of our development programme. We have designed the programme to provide the required data to Authorities so that the benefit-risk of RG6042 can be determined as quickly as possible. Our ultimate goal is that this investigational medicine can be approved by Health Authorities, and made accessible to the broader HD community.

Can I access RG6042 outside of clinical studies?

At this time, access to RG6042 is only through clinical study participation because the benefits and risks of RG6042 are not yet fully understood. This means that we are not able to grant pre-approval, compassionate use or “right-to-try” requests at this time. As our understanding of the benefits and risks of RG6042 grows, we will regularly evaluate this position.

Your clinical studies are in early manifest and manifest HD. Will you study RG6042 in other patient populations (e.g., juvenile onset HD, pre-manifest or prodromal HD)?

We recognise the critical medical need for a treatment for HD, especially for people living with severe forms like juvenile onset HD. In consultation with HD community experts, our team will explore the potential use of RG6042 in populations beyond manifest HD once there is sufficient scientific and safety rationale.

For the Phase III GENERATION HD1 study, how are you ensuring scientific rigour?

Pending approval by Health Authorities and Ethics Committees/IRBs, the GENERATION HD1 study will be a multi-centre, randomised, double-blind, placebo-controlled study, which is considered a “gold-standard” research approach to avoid biased study results. These terms mean:

  • Multi-centre: The study will occur at multiple sites with different investigators and staff
  • Randomised: The process by which study drug (active or placebo) will be assigned to participants is by chance (random), and not by choice. Based on study design, for every two participants randomised to RG6042, one will receive placebo
  • Double-blind: Neither the participant nor his/her investigator or site staff will know which study arm (treatment or placebo) the participant is assigned
  • Placebo-controlled: The investigational medicine, in this case RG6042, will be compared against the use of a placebo

What is the placebo in GENERATION HD1, and why is it being used?

The placebo that will be used in the planned GENERATION HD1 study is an inactive substance. The placebo will look like RG6042 (a clear liquid) and will be injected into the body using the same intrathecal (lumbar puncture) procedure, but it is not active drug.

As we enter the final phase of clinical development with a global Phase III study in manifest HD, it is important to determine if potential effects or safety concerns observed in the study are due to RG6042 treatment – and not to other effects (for example, expectations of anyone involved with the clinical study). This information is critical to provide to Authorities to help them determine the benefit-risk of treatment with RG6042.

Dr. Ed Wild posted live updates from the European Huntington Disease Network Conference in Vienna on HDBuzz’s Twitter feed.

Please see full Twitter thread here.

Read the full French community letter here.


August 2018 Update:

PRIME Designation Granted by European Medicines Agency for RG6042 for Treatment of Huntington disease

On August 2, 2018, Roche and IONIS announced through a press release (click here to read the full release) that the Huntingtin lowering therapy RG6042 has been granted PRIME designation by the European Medicines Agency.

What did the press release say?

  • The press release said that European Medicines Agency (EMA) has granted PRIME (PRIority MEdicines) designation for Roche’s medicine RG6042 (formerly known as IONIS-HTTRx) for the treatment of people with Huntington disease (HD).

What is PRIME?

  • PRIME is a European Medicines Agency (EMA) initiative. PRIME was launched to enhance support for the development of medicines that target an unmet medical need.
  • PRIME offers support to enhance data collection on the medicine’s benefits and risks, and provides an accelerated pathway of evaluation. PRIME’s goal is to help patients benefit as quickly as possible.

What does this mean for the Canadian HD Community?

  • This is positive news as the PRIME designation is a sign of progress as Roche continues to engage with global health authorities on the Phase III study of RG6042 and how to advance this program quickly.
  • 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. HD-COPE is meeting regularly with Roche.
  • Finally, we continue to provide trial details and contact information for open research studies on our website at huntingtonsociety.ca/clinical-trial-locations. (Please note that the upcoming Roche trial has not yet begun, the clinical sites have not been announced and is so it is not listed there for that reason.)

What is next?

  • Roche continues to work on their plans for a longer, larger global study of RG6042. The goal of that study is:
    • To determine what are the effects on lowering the huntingtin protein over a longer period of time than the 13-week Phase I/IIa study?
    • To find out if any unexpected safety concerns emerge when a larger group of people are treated for a longer period of time?
    • To determine if sustained treatment with RG6042 has an impact on HD by slowing down the progression?
  • Specific details will be provided as soon as they are available including study sites and dates.
  • If you have questions, we recommend that you contact your local neurologist, Movement Disorders or Huntington disease clinic.


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.

Sincerely,
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 www.huntingtonsociety.ca/clinical-trial-locations/  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 www.huntingtonsociety.ca/clinical-trial-locations/. 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 www.huntingtonsociety.ca/hd-clinical-trials  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.

Sincerely,
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.

IONIS HUNTINGTIN-LOWERING TRIAL INFORMATION:

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.

Sincerely,

Your Roche & Ionis Team

Click here to read the original statement.


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