SAGE Therapeutics — CNS Disorders

[Autumnly]

Sage Therapeutics
"Sage Therapeutics is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing novel medicines to transform the lives of patients with life-altering central nervous system (CNS) disorders."

SAGE-217
"SAGE-217 is a novel, selective, next generation GABAA positive allosteric modulator that shares similar pharmacology properties to brexanolone. We are initially developing SAGE-217 as a once-daily, oral therapy for treatment of various CNS disorders."

Sage Announces Pivotal Phase 3 Trial Status for SAGE-217 in Major Depressive Disorder and Postpartum Depression based on FDA Breakthrough Therapy Meeting

• Expedited SAGE-217 development plan to support potential NDA submission for MDD and PPD
• Previously completed placebo-controlled study in MDD considered as pivotal; initiation of one additional Phase 3 pivotal trial anticipated in 2H of 2018.
• Ongoing study in PPD designated as pivotal; results expected in 4Q 2018.
• If successfully developed, SAGE-217 has the potential to be the first durable, rapid-acting, oral, short-course treatment for MDD and PPD

Further Exploitation of GABAA and NMDA Receptors
"We are exploring additional potential products in a variety of CNS disorders based on modulation of both the GABAA and NMDA receptors. In addition to our products focused on SE, other GABAA mediated CNS disorders upon which we believe our approach can have a material impact include Rett syndrome, Dravet syndrome, fragile X syndrome, anxiety, depression, sleep disorders, mania, tremor, tinnitus and post-traumatic stress disorder."

"Enhancing GABA pharmacologically (benzodiazepines) or physiologically (more Typer II or somatosensory inputs) could quiet tinnitus" - Dr. Robert Aaron Levine

 

[Contrast]

hey i posted that video earlier

 

[Greg Sacramento]

@Contrast I also posted what @Autumnly posted, but I'm glad that she reposted it because I can't post more as I recently bought shares 3 weeks ago. With that I think that the share price is too high. I'm going to sell tomorrow.

 

[PetitGarsTimide]

SAGE-217 is the new xanax

 

[Autumnly]

There's also brexanolon (formerly known as SAGE-547) which is administered as an intravenous therapy designed to correct imbalances in GABA signaling within the brain. It's an acute interventional treatment for postpartum depression and already through phase 3. The FDA has accepted the filing of a New Drug Application and granted Priority Review status.

But I have no idea which drug (brexanolon or SAGE-217) would be more effective in treating tinnitus (if they can actually treat tinnitus).

 

[Paulmanlike]

There's also brexanolon (formerly known as SAGE-547) which is administered as an intravenous therapy designed to correct imbalances in GABA signaling within the brain. It's an acute interventional treatment for postpartum depression and already through phase 3. The FDA has accepted the filing of a New Drug Application and granted Priority Review status.

But I have no idea which drug (brexanolon or SAGE-217) would be more effective in treating tinnitus (if they can actually treat tinnitus).

Does anybody know if this drug being developed by SAGE working on correcting the GABA has helped tinnitus?

 

[Greg Sacramento]

@Paulmanlike

Does anybody know if this drug being developed by SAGE working on correcting the GABA has helped tinnitus?

The company won't comment on that. Maybe they will with other design therapy.

All drugs of this nature will probably require IV injection as this one with approval in link below for 60 hours. Will healthcare consider it cost effective to treat tinnitus with IV injection long term. This may be the reason for SAGE holding back on a direct GABA treatment for tinnitus. It's important as an awareness cause to have hospitals and doctors realize that tinnitus is a severe condition.


https://www.fiercebiotech.com/biotech/fda-panel-backs-sage-s-postpartum-depression-drug-17-1-vote

 

[Paulmanlike]

@Paulmanlike

The company won't comment on that. Maybe they will with other design therapy.

All drugs of this nature will probably require IV injection as this one with approval in link below for 60 hours. Will healthcare consider it cost effective to treat tinnitus with IV injection long term. This may be the reason for SAGE holding back on a direct GABA treatment for tinnitus. It's important as an awareness cause to have hospitals and doctors realize that tinnitus is a severe condition.


https://www.fiercebiotech.com/biotech/fda-panel-backs-sage-s-postpartum-depression-drug-17-1-vote

SAGE has got a Buy rating, I saw you previously bought stock in the company, did you sell it in the end or you holding on?

 

[Autumnly]

Sage Therapeutics to Provide Update on Key 2019 Initiatives at J.P. Morgan Healthcare Conference

• Launch of ZULRESSO (brexanolone) in the U.S., if approved, will follow the anticipated scheduling of brexanolone by the Drug Enforcement Administration (DEA), and is projected for June 2019.
• Statistically significant results achieved in Phase 3 trial of SAGE-217 in postpartum depression
• First patient dosed in second pivotal trial of SAGE-217 in major depressive disorder

 

[Greg Sacramento]

SAGE is in completion of raising 575 million to add to the hundreds of millions that they already have in the bank.

In the last year they have been putting together what appears to be a solid patent library of compounds for tinnitus.

Neuroactive steroids, compositions, and uses thereof

Three of their many patents

(1) Provided herein are 19-nor C3, 3-disubstituted steroids of Formula (I): and pharmaceutically acceptable thereof; wherein R1, R2, R3, and R4 are as defined herein, and A is a heteroaryl ring system comprising 3 or 4 nitrogens as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, traumatic brain injury, vascular diseases, substance withdrawal syndromes, and tinnitus.

19-nor neuroactive steroids and methods of use thereof

(2) Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, pain, traumatic brain injury, vascular diseases, withdrawal syndromes, tinnitus, . Brain Cognition Diseases Mood Disorder Personality Disorder Sleep Disorder Tinnitus Traumatic Brain Injury Vascular Diseases

(3) Neuroactive steroids, compositions, and uses thereof
Described herein are steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein R1, R2a, R2b, R3, R4, R5a, R5b, R6, and Z are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus

Behind '547, Sage is developing a spate of CNS therapies that modulate the brain's GABAA and NMDA receptors, including preclinical treatments for depression, essential tremor, tinnitus and pain.

Last year I posted a form where one could just type 'please develop a tinnitus drug as soon as possible'.

Their depression drug is a non benzo with hardly any taper needed.
In my opinion they could raise another 2 to 3 billion from Wall Street with no problems.

Awareness - Go to the money that has research and the patents. Someone that can save us and not some treatment that might help a small percentage.

 

[Arseny]

So this might come out in 3 months?
Is anyone going to try it?
I imagine you have to travel to USA to try it?

 

[Greg Sacramento]

So this might come out in 3 months?

Your reference is to a depression non benzo non taper neuro depression drug. This is a first in class and most have thought that it was impossible. I have no idea if it will help with tinnitus and the company won't discuss this as it's not part of label.

They are doing neuro research on tinnitus and pain, but in their conference call they are at present focusing on other neuro disease and conditions. Can they do the impossible with a tinnitus drug even though it may take years to develop? They have important patents that may slow others down with tinnitus research.

I think that this is our only hope as tinnitus is a neuro brain disease. I just think that most to all other treatments will just make money for those with these procedures and for those within these communication areas.

There's a few with physical tinnitus of more than one year that do see their tinnitus fade due to physical treatments. A few more will receive lowering, but healthcare often doesn't investigate and use research study. Studies have recently come out and said that certain tests are needed for physical tinnitus which include a FONAR stand up MRI for the neck and 3D cone beam scan for jaw.

 

[Paulmanlike]

@Greg Sacramento can you please provide links to SAGE Therapeutics where they say they are doing research into tinnitus drug treatments?

 

[Jazzer]

Awareness - Go to the money that has research and the patents. Someone that can save us and not some treatment that might help a small percentage.

This is the only real hope of a breakthrough that I personally have.
The idea of gizmos relaying electric currents to already damaged nerve cells sounds very dodgy to me; it could have the potential for further damage I reckon.
It all looks like a 'hit and miss - trial and error' set up, rather than genuine science.
Drugs can effectively treat headaches, migraines, Parkinson's, anxiety, and tons of other conditions.
Before Greg brought this up I hadn't seen any reference to it?
We just have to hope.....x

 

[Greg Sacramento]

can you please provide links to SAGE Therapeutics where they say they are doing research into tinnitus drug treatments?

Besides with tinnitus patent registrations it mentioned in the other SAGE thread.
They are doing some serious tinnitus patent collecting and they have a strong BOD presence in the tinnitus space.
Jeff Jonas
https://www.sagerx.com/about-us/our-team/

With this, I would think that a Phase I will be coming in a few years if not sooner.
I personally will not make an investment because EPS earnings per share is expected to drop going into 2020. From about -2.00 to over -10.00. That's would be a big drop in earnings per share.

 

[Paulmanlike]

@Greg Sacramento

It seems they have a bunch of patents looking for a nail to hit with a hammer.

I contacted SAGE regarding their patents and asked if they had any plans to initiate any trials for tinnitus.

As expected they said they cannot discuss this unfortunately, and gave me links to their clinical trials and pipeline.

 

[shasta0863]

Any update to this?

 

[Autumnly]

Any update to this?

• SAGE-217 is still in Phase 3
• Sage Therapeutics Announces U.S. Drug Enforcement Administration Scheduling of ZULRESSO™ (brexanolone) Injection
  • was approved by the U.S. Food and Drug Administration (FDA) on March 19, 2019
    
  • first and only treatment specifically approved for postpartum depression (PPD)
    
  • The Company expects to launch ZULRESSO in late June as planned.
  • ZULRESSO is administered via continuous intravenous (IV) infusion for 2.5 days under the supervision of healthcare providers in sites of care certified under the ZULRESSO Risk Evaluation and Mitigation Strategy (REMS) program. The one-time infusion offers the potential for rapid resolution of depressive symptoms of PPD.
• Still don't know if these drugs could help with tinnitus

 

[TheDanishGirl]

Stumbled upon this news, from December 5:

Sage crushed by MOUNTAIN as phase 3 depression data fall short''
https://www.fiercebiotech.com/biotech/sage-crushed-by-mountain-as-phase-3-depression-data-fall-short

So I guess that's that......another miss.

 

[Piney]

That video on fusiform cells was awesome. They mention electrical stimulation to alter the imbalance, isn't that what Susan Shore is attempting? My first few months with tinnitus I can remember taking GABA pills as the anxiety hit a ceiling, I believe it lowered it and brought my back to earth for a little while. Maybe she is on to something. I hope they don't give up on the drug, more drugs the better in the direction of possible treatment, not sure how it would help depression though. I would think something that stimulates you might be better but what do I know? I'm no doctor.

 

[InNeedOfHelp]

An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus

A new trial is underway.

 

[Nick47]

An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus

A new trial is underway.

I wonder why they exclude hearing loss?

 

[juliob]

In theory, would those undergoing benzo tapering or benzo withdrawal be playing with fire taking this?

 

[Watasha]

In theory, would those undergoing benzo tapering or benzo withdrawal be playing with fire taking this?

Inclusion criteria for the new study:

Participant is willing and able to safely discontinue the use of central nervous system (CNS) depressants (e.g., opioids and benzodiazepines), antidepressants, anticonvulsants, CNS stimulants (with the exception of caffeine), aspirin, other nonsteroidal anti inflammatory drugs, and aminoglycosides at least 14 days or 5 half-lives (whichever is longer) prior to receiving IP and through completion of the study

An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus​

 

[Travis Henry]

Where is the hype on this one?

 

[Nick47]

Where is the hype on this one?

I think the lack of hype is out of partial surprise (it has come out of nowhere) and the fact they have not put forward a scientific rationale for this.

The active component has been on the market for around 3 years, given for post natal depression. It's been effective but highly expensive.

@Greg Sacramento will be the one to ask judging by his previous contributions to this thread in terms of scientific rationale.

But a piece written recently states:

Brexanolone (Zulresso) is a mixture of allopregnanolone and sulfobutylether-beta-cyclodextrin, acts as an anti-depressant. It is formulated as injectable solution for intravenous route of administration. Zulresso is indicated for the treatment of postpartum depression (PPD) in adults. Zulresso is indicated for the treatment of postpartum depression in patients 15 years of age and older.

SAGE-547 (SGE-120) is under development for the treatment of severe postpartum depression (PPD), Post-traumatic stress disorder (PTSD), psychosis, tinnitus and alcohol addiction. The drug candidate is administered through intravenous injection. The drug candidate is a formulation of allopregnanolone, a metabolite of progesterone formed in the CNS. It is a positive GABAA receptor allosteric modulator. The drug candidate is based on positive and negative allosteric modulator (PANAM) chemistry platform. The PANAM technology comprises of non-benzodiazepine approach that regulates allosteric modulation of GABAA receptor in the positive (PAM) direction. It was also under development for the treatment of super-refractory status epilepticus (SE), traumatic brain injury, major depressive disorder, Alzheimer's disease, mild cognitive impairment, COVID-19 related acute respiratory distress syndrome (ARDS) and essential tremor.​

The trial starts in a matter of weeks...

 

[IndyMLVC]

Inclusion criteria for the new study:

Participant is willing and able to safely discontinue the use of central nervous system (CNS) depressants (e.g., opioids and benzodiazepines), antidepressants, anticonvulsants, CNS stimulants (with the exception of caffeine), aspirin, other nonsteroidal anti inflammatory drugs, and aminoglycosides at least 14 days or 5 half-lives (whichever is longer) prior to receiving IP and through completion of the study

An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus​

I was asked to do a study on a medication like this (I don't think this was it). The idea of being off ALL antidepressants/anxiety meds plus edibles on the off chance that I don't get the placebo is too much for me. Then the fact that, IF you get the real thing AND it works, they take it away afterwards would frustrate me to no end.

 

[InNeedOfHelp]

I guess the actual goal or Brexanolone for tinnitus might be treating tinnitus/hyperacusis related depression.

Their launch focus is treatment resistant depression. One of their targets (patient burden definitions) is delayed or impaired long-term developmental, psychological, cognitive and physical burden.

The source for this goal comes from the following source:

Parental Mental Health in Childhood as a Risk Factor for Anxiety and
Depression among People Seeking Help for Tinnitus and Hyperacusis

This can be found in their yearly report:

Sage Therapeutics - Fourth Quarter and Full Year 2022 Financial Results

Basically this looks far-fetched, with the reason that it is most likely far-fetched. Seems like a shot of hail to get more indications approved for this medicine. I haven't come across any evidence that it actually lowers tinnitus as of yet, and, as usual, the company does not answer their e-mails.

 

[Nick47]

I guess the actual goal or Brexanolone for tinnitus might be treating tinnitus/hyperacusis related depression.

Their launch focus is treatment resistant depression. One of their targets (patient burden definitions) is delayed or impaired long-term developmental, psychological, cognitive and physical burden.

The source for this goal comes from the following source:

Parental Mental Health in Childhood as a Risk Factor for Anxiety and
Depression among People Seeking Help for Tinnitus and Hyperacusis

This can be found in their yearly report:

Sage Therapeutics - Fourth Quarter and Full Year 2022 Financial Results

Basically this looks far-fetched, with the reason that it is most likely far-fetched. Seems like a shot of hail to get more indications approved for this medicine. I haven't come across any evidence that it actually lowers tinnitus as of yet, and, as usual, the company does not answer their e-mails.

@InNeedOfHelp, at first, and given it's been in clinical use a few years, I could only think that several patients had commented to clinicians that it's lowered the volume of their tinnitus/hyperacusis.

Then like you said, they have trialled it to expand its possible clinical use.

The link you've found is very tentative indeed.

The primary outcome is safety, however the secondary measures are tinnitus 'loudness' and annoyance.

 

[InNeedOfHelp]

@InNeedOfHelp, at first, and given it's been in clinical use a few years, I could only think that several patients had commented to clinicians that it's lowered the volume of their tinnitus/hyperacusis.

Then like you said, they have trialled it to expand its possible clinical use.

The link you've found is very tentative indeed.

The primary outcome is safety, however the secondary measures are tinnitus 'loudness' and annoyance.

View attachment 53515

It surprised me that they measure tinnitus loudness. Might be the GABA part.

I think their aim is simply getting a tinnitus approved indication since there is nothing formally approved for us. I guess it will result in a similar outcome as if Amitriptyline/Mirtazapine was trialed for tinnitus which would surely give a statistically significant outcome versus placebo. You can get an antidepressant approved for 1000s of chronic disorders. So it is more a "strategic" trial to get some market share in an untouched market. Especially because there is no published rationale or mentioning of tinnitus anywhere in their report.

I'm speculating but I'm not interested in this one.