ATA188

[tzootsi]

https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=1

[Tif]

hi all,
is anyone on here doing the study?
i tried but having done stem cells prevents me, it's an exclusion

tif

[Scott1]

Hi,
It looks this is still a long way from a conclusion and the study groups are small.
This presentation was included at last years ECTRIMS conference
https://www.neurologylive.com/view/ata1 ... sion-study

At the 8.40 mark in this video, made in mid 2021, the company behind ATA188 talks about the results to date (The presenter has a pronounced accent!)


Regards,

[Tif]

Thanks for posting the video.

https://www.atarabio.com/science-and-technology/

i'm hoping the ebv angle comes to fruition.

[NHE]

Atara highlights long-term data from early-stage ATA188 multiple sclerosis trial

Oct 13, 2021 8:06 AM ET | Atara Biotherapeutics, Inc. (ATRA) | Aakash Babu, SA News Editor

Atara Biotherapeutics (NASDAQ:ATRA) announces new translational and updated Phase 1 open-label extension (OLE) clinical data in patients with progressive multiple sclerosis (MS) treated with ATA188 for up to 39 months.

ATA188 is an investigational, off-the-shelf, allogeneic T-cell immunotherapy that targets Epstein-Barr virus (EBV)-infected B cells and plasma cells.

Of 24 patients who received ATA188, and in which efficacy was evaluated in the initial 12-month period, 18 patients chose to participate in the OLE and were followed for up to 39 months.

Of the 18 patients in the OLE, nine achieved sustained disability improvement (SDI) either in the initial 12-month period (n=7) or in the OLE (n=2) and of these, seven patients had sustained Expanded Disability Status Scale (EDSS) improvement.

A relationship between dose-escalation and increasing clinical response was observed, with seven of nine patients that achieved SDI receiving the two highest doses either initially or in the OLE, the company said.

Eight patients that achieved SDI participated in the OLE, and seven of these maintained SDI at all subsequent timepoints.

The median time for which SDI was maintained in these eight patients was 18 months (range 0.03–27.0 months).

Atara highlighted that it continues to enroll patients in the mid-stage trial of ATA188 in the treatment of patients with progressive MS with a planned interim analysis in the first half of next year.

[Tif]

i'm hoping that between killing off the ebv, and having stem cells to go to work and repair the damage done, we can be normal again.

if people see improvements with 'only' killing off of the virus, and the body's own healing ability. how about killing ebv, get stem cells to do the repair afterwards?

thoughts?

[Tif]

hi,
"SHERBROOKE, QC, Jan. 11, 2022 /PRNewswire/ -- Imeka, the leading neuroimaging company combining diffusion imaging and AI to map white matter integrity, today announced a collaboration with Atara Biotherapeutics, Inc. to utilize Imeka's novel biomarker technology in a Phase 2 clinical study of patients with progressive forms of multiple sclerosis (MS). Imeka's non-invasive Advanced Neuro Imaging Endpoints (ANIE) biomarker platform will measure the potential effect of Atara's investigational treatment, ATA188, on neuroinflammation and remyelination in the brain and spinal cord in patients with primary progressive MS and secondary progressive MS. ...."

https://www.prnewswire.com/news-release ... 57246.html

i wanted to add: https://imeka.ca/why/

i hope all of it works....but don't we all..

[Tif]

https://clinicaltrials.gov/ct2/show/NCT02822495

Study Type : Expanded Access
Official Title: Expanded Access Protocol for Providing Tabelecleucel to Patients With Epstein-Barr Virus-Associated Viremia or Malignancies for Whom There Are No Appropriate Alternative Therapies

Intervention Details:
Biological: tabelecleucel
Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
Other Names:
tab-cel®
ATA129
EBV-CTL

'...Brief Summary:
The primary objective of this protocol is to provide expanded access to tabelecleucel to participants with Epstein-Barr virus-associated diseases and malignancies for whom there are no other appropriate therapeutic options, and who are not eligible to enroll in clinical studies designed to support the development and registration of tabelecleucel.

Condition or disease Intervention/treatment
Epstein-Barr Virus (EBV) Infections
Lymphoproliferative Disorders
EBV+ Associated Lymphoma
EBV+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)
Epstein-Barr Viremia
Lymphoma, AIDS-related
Epstein-Barr Virus-associated Lymphoproliferative Disease (EBV+ LPD) With Primary Immunodeficiency (PID)
Leiomyosarcoma (LMS)
Nasopharyngeal Carcinoma (NPC)
Epstein-Barr Virus-associated Lymphoproliferative Disease (EBV+ LPD) With Acquired Immunodeficiency (AID)
Solid Organ Transplant Complications
Stem Cell Transplant Complications
Biological: tabelecleucel

Detailed Description:
Participants for whom there are no other appropriate therapeutic options and who are not eligible to enroll in other tabelecleucel clinical studies, may be enrolled in this study. After the screening period, participants will receive intravenous infusions of tabelecleucel (1.6 to 2 × 10^6cells/kg) on Day 1, Day 8, and Day 15 of every 35-day cycle. Clinical assessment of disease response is recommended approximately 15 days after the last dose of tabelecleucel to assess the need for additional treatment. The end of expanded access protocol (EAP) visit should be performed at 30 days after the last dose of tabelecleucel.
.....'

[NHE]

ATA188 fails phase 2 trial, ATA Stock falls 82%...

Atara Biotherapeutics Announces Primary Analysis Data From Phase 2 EMBOLD Clinical Trial of ATA188 in Non-active Progressive Multiple Sclerosis

November 08, 2023 5:35 pm EST

https://investors.atarabio.com/news-eve ... -data-from

Primary Endpoint of Confirmed Disability Improvement at 12 Months Not Achieved

Company to Further Analyze Data and Evaluate Strategic Options for ATA188 Program with Focusing of Resources and Planned Expense Reductions Expected to Extend Cash Runway Beyond Q3 2025

Allogeneic CAR-T Portfolio Advancing with Several Catalysts Anticipated in the Next 18 Months

THOUSAND OAKS, Calif.--(BUSINESS WIRE)-- Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, today announced primary analysis data from its Phase 2 EMBOLD study of ATA188 in non-active progressive multiple sclerosis (PMS). The study did not meet the primary endpoint of confirmed disability improvement (CDI) by expanded disability status scale (EDSS) at 12 months compared to placebo. In addition, fluid and imaging biomarkers did not provide further supportive evidence.

"We are surprised and deeply disappointed with the results of EMBOLD, particularly for the MS patient community which is in urgent need of new treatment options. We are grateful to the patients and investigators who participated in the study, and to colleagues at Atara for their steadfast work,” said Pascal Touchon, President and Chief Executive Officer of Atara. “We are further evaluating the EMBOLD data as we continue to believe in the critical role EBV plays in MS pathogenesis, however we anticipate stopping the study as no treatment benefit was observed.”

Preliminary safety data showed there were no new safety signals in the EMBOLD study, reinforcing the favorable safety profile observed with ATA188 to date.

Atara is actively reviewing the totality of the data, including a 6 percent disability improvement in the treatment arm compared to 33 percent disability improvement observed in the Phase 1 study, in addition to identifying the factors related to a substantially greater than expected placebo rate of 16 percent for CDI at 12 months compared with an expected rate of 4-6 percent in non-active PMS patients. These evaluations will help Atara determine the next steps for the program.

“Looking ahead, we maintain our strong conviction in the potential of our pipeline reinforced by the first ever regulatory approval of an allogeneic T-cell immunotherapy, EBVALLOTM, in Europe,” Dr. Touchon continued. “Following anticipated additional payments and significant double-digit royalties from the recently expanded tab-cel® partnership with Pierre Fabre, we are currently well positioned with a cash runway well beyond upcoming milestones, including pre-clinical data for ATA3431 at ASH in December, preliminary clinical data from our Phase 1 study of ATA3219 in relapsed/refractory B-cell non-Hodgkin’s lymphoma anticipated in the second half of 2024, and expanding ATA3219 development into autoimmune disease.”

Going forward, the Company plans to significantly reduce its expenses on ATA188 and further focus resources on advancing its differentiated allogeneic CAR-T pipeline, in addition to executing the expanded tab-cel partnership with Pierre Fabre through the Biologics License Application (BLA) transfer. These future actions are expected to meaningfully extend our cash runway beyond Q3 of 2025.

[Scott1]

Hi,
"The study did not meet the primary endpoint of confirmed disability improvement (CDI) by expanded disability status scale (EDSS) at 12 months compared to placebo."

Frankly, it's an absurd end point to pick. Most confirmed disability relates to motor pathway damage. That arises as a consequence of demyelination. When you are born, the process of axons being coated with myelin is near its beginning. It may have started in the 14th week of fetal development but new born babies don't get up and go for a stroll on day 1 because there is minimal myelin formation in the brain at birth. Growing myelin depends on dietary fats and is a process that takes until adolescence to complete. Building neural pathways takes a long time and dead neurons don't recover- they're dead.

So, if you have lesions on your motor pathways, it reasonable to assume there is damage to neurons, myelin producing oligodendrocytes and the astrocytes that pass nutrients from the blood vessels to the neurons. If all those things are damaged, why on earth would you think that eliminating a possible cause would magically reverse that damage? It is like arguing that person killed by a stab wound would recover if you pulled the knife out. It's not even slightly logical.

Obviously, they are off to concentrate elsewhere, but I don't understand why they didn't do a more detailed analysis of the affect on EBV itself.

Regards,

[NHE]

Perhaps instead of “confirmed disability improvement,” it may have made more sense to look at the prevention of disability progression.

[Scott1]

Maybe. It's hard to stop a speeding train. They started with people with advanced EDSS. Once motor problems are established they can take on a life of their own. Hence, people doing exercise or some manual therapies sometimes see improvement.
Why didn't measure fatigue or cognitive issues.
It's not really clear what the other measure they tested were but antibodies to EBV antigens don't absolutely imply a current problem.

[CureOrBust]

Why didn't measure fatigue or cognitive issues.

I was in the open label study for about 4 years. They did measure cognitive issues (PSAT and memory tests) and did the fatigue questionnaire (self reported) at every visit, and suicide potential checks. This was of course in addition to physical performance (25ft walk etc), and a few eye sight tests; distance/accuracy and contrast/color distinction. As well as a general overlook at your symptoms by a neuro, such as for nystagmus etc etc

It's not really clear what the other measure they tested were but antibodies to EBV antigens don't absolutely imply a current problem.

I had many blood tests at every visit. I think the antigen blood test was mainly used to match you to a formulation, and not ran at every visit (I could be wrong on that one.

I think the level of EBV antigens may of been used to show the underlying infection levels still present.

[NHE]

Hi Cure,

I was in the open label study for about 4 years. They did measure cognitive issues (PSAT and memory tests) and did the fatigue questionnaire (self reported) at every visit, and suicide potential checks. This was of course in addition to physical performance (25ft walk etc), and a few eye sight tests; distance/accuracy and contrast/color distinction. As well as a general overlook at your symptoms by a neuro, such as for nystagmus etc etc.

Did you find out which treatment you were receiving, the ATA188 or the control?

How were your MS symptoms during the 4 year study?

[CureOrBust]

It was OPEN LABEL, dose increase test in prep for phase III. I WAS given the real stuff, but was on the second highest dose, not the highest dose, which is what they went for in the Phase III. I did get two infusions (ie 2 years) at the full dose as part of an extension study. It did not work for me (hence I left the study during the extension), and I guess it wasnt working now in the phase III.

But, bad news, I saw the neurologist that was running the study here in sydney, and she said it had failed. Also some other one I had never heard of. I am, *guessing* it is this one.
https://multiplesclerosisnewstoday.com/ ... olunteers/