FDA Advisory Committee Votes 17-1 in Support of Zulresso for PPD

Today the Advisory Committee (ADCOM) voted 17-1 in support of Sage Therapeutics drug Zulresso for Postpartum Depression (PPD). The first and only drug if approved for this unmet medical need, will go into commercialization early 2019 under the name of Zulresso. The press release is here FDA Advisory Committee Votes 17-1. 
The future for the company gets even more exciting with once daily oral drug SAGE-217, which is in phase 3 testing for Major Depressive Disorder or MDD, and has a market potential several times larger than PPD.
SAGE has a talented management team, with plenty of cash to run pivotal clinical trials, and bring new drugs for other indications to market. SAGE-217 has patent to April 2034. Thank you for reading.
 

Neuroactive Steroids (NAS)

Not all neuroactive steroids are created equal from this chart and abstract below. That may be important when comparing Sage Therapeutics SAGE-217 to Marinus Pharmaceuticals drug Ganaxolone for patients with Postpartum Depression. First let's look at a chart that compares oral SAGE-217 to IV SAGE-547 and IV Ganaxolone for synaptic and extrasynaptic activity of each.

 

SAGE-217 shows much more activity in both synaptic and extrasynaptic activity over a given time period.  Below is another illustration that not all is created equal when considering tonic current. https://www.ncbi.nlm.nih.gov/pubmed/27743930. Here is a paragraph from that abstract.

A sustained increase in tonic current was observed following exposure to ALLO, or SGE-516 and was prevented by inhibiting PKC with GF 109203X. No increase in tonic current was observed with exposure to ganaxolone. In agreement with the observations of an increased tonic current, the NASs ALLO and SGE-516 increased the phosphorylation and surface expression of the β3 subunit-containing GABAARs. Our studies demonstrate that neuroactive steroids have differential abilities to induce sustained increases in the efficacy of tonic inhibition by promoting GABAAR phosphorylation and membrane trafficking dependent on PKC activity.

Thank you for reading.

SAGE Therapeutics Market Capitalization in Charts - $183.47

Sage Therapeutics - (SAGE) has a CNS drug with a unique fast acting mechanism of action, that has led the company to a current $7.41 billion dollar market capitalization. Previous writing's  about the company can be found here SAGE. Below is a market capitalization chart of SAGE, at certain stock prices.

The current market capitalization of the company is around $7.41 billion. We see SAGE reaching a $10 billion market cap ($240.00) in the near future based solely on their current pipeline, potentially reaching a $15 billion market cap ($361.00) on further success for SAGE-217 in other indications, and potential buyout of the company. The patent for SAGE-217 and SAGE-547 run to 2034. Thank you for reading.

Contact: 586-431-8000

Super Refractory Status Epilepticus (SRSE)

Sage Therapeutics - SAGE, is currently in phase 3 for unmet need (SRSE) with drug SAGE-547.   SRSE is a rare neurological condition, and a sub-type of Status Epilepticus (SE), which is a prolonged seizure.  A diagram from this link explains the stages. The Treatment of Super-refractory Status Epilepticus.

Click to Enlarge 

SAGE Therapeutics has a Special Protocol Assessment (SPA) with the FDA for this phase 3 clinical trial.  The company mentioned, that Refractory Status Epilepticus (RSE) has up to 50% response rate, and that (SRSE) has approximately 35% response rate.  The trial should complete first half of 2017.  Thank you for reading.        

SAGE-217 Patent Issued

SAGE-217 was issued patent number US 9,512,165 B2, which runs to April 2034.  The link to other patent applications can be found here SAGE Patent Applications.  SAGE-217 is the oral version of SAGE-547, and will be running four proof-of-concept, phase 2 clinical trials in 2017.  Thank you for reading.                

SAGE-547 Expedited Pathway Revealed

We initially wrote about Sage here, SAGE-547.  This week SAGE revealed through this press release Sage Therapeutics, the expedited pathway for drug SAGE-547 for Postpartum Depression.  The important news was that the FDA in agreement with Sage, anticipates that no additional controlled studies will be necessary to file an NDA.  The company believes that they may be able to file for a new drug application for Postpartum Depression in 2018.  If approved by the end of 2019, the company will have patent until around 2034, or approximately 15 years of exclusivity.  Below are the important aspects of the expedited pathway for SAGE-547, agreed upon by the FDA.

• Current SAGE-547 clinical studies confirmed as appropriate to support registration, if successful
• No additional efficacy studies expected to be required beyond those currently underway
• Trial design of studies 202B and 202C are considered appropriate for registration, with increase in size and other minor modifications
• The primary clinical endpoint for these pivotal trials was unchanged and agree upon with FDA
• Additional patient safety data may be acquired through an open-label program

Below is a year-to-date chart of SAGE.  Despite the company having an extraordinary year with SAGE-547 the stock is down -4.49% this year.  The company currently has $431 million in cash, or about $13.00 per share in cash.  

Source: Shaw Investments, StockCharts.com

Thank you for reading.                

SAGE-217

The future pipeline will be more dependent upon SAGE-217, which is built around the same premise as SAGE-547, but as a once daily oral delivery. 
The company describes SAGE-217 as "a novel neuroactive steroid that acts as a positive allosteric modulator of synaptic and extra-synaptic GABAa receptor subtypes.  Unlike many of the naturally occurring neuroactive steroids, SAGE-217 has a pharmacokinetic profile to potentially support once-daily oral dosing and a selectivity profile that minimizes potential off-target side effects." 

Patents: SAGE-217 to April 2034

Bottom Line:
Sage Therapeutics is an interesting company with plenty of cash and a very successful phase 2 clinical trial completed.  The future will be focused on their oral, once daily SAGE-217.  Thank you for reading. 

SAGE-547 for Postpartum Depression

Sage Therapeutics (SAGE) stock soared higher by 37% on the companies phase 2 data release, for the indication of severe Postpartum Depression or PPD.  SAGE-547 has a differentiated mechanism of action (moa), and clean safety profile.  From their press release today.  

"SAGE-547 achieved primary objective with a significant reduction in HAM-D total score compared to placebo at 60 hours (p=0.008).  Baseline mean HAM-D scores were severe (28.1 for SAGE-547; 28.8 for Placebo), SAGE-547 showed reduction in HAM-D of greater than 20 points at 60 hours.  Improvement was 12 points greater vs. placebo.  Improvement maintained through 30-day follow-up (p=0.01)."

Quick Facts:
Shares Out 32M
Market Cap:  $1.2b
Cash:  150m
Patent:  2034

These results in PPD, signal the potential for other CNS uses.  SAGE-547 works very rapidly, and maintained the results through the 30 day follow-up period.  Thank you for reading.