Friday, January 6, 2017

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.


Friday, December 30, 2016

SAGE-217 Clinical Trial Progress

Sage Therapeutics' SAGE-217 is the companies next generation oral CNS drug for a variety of indications.  The company has completed the required phase 1 studies, and is now running phase 2, proof of concept clinical trials listed below with expected readout of data.  The four clinical trials can be found at here SAGE-217.

Severe Postpartum Depression - June 2017
Essential Tremor - December 2017
Moderate to Severe Major Depressive Disorder - December 2017
Parkinson's Disease of Moderate Severity - June 2017

Sage Therapeutics has many clinical trials currently running.  The company has $431 million in cash, and patent to 2033.  Thank you for reading. 


Friday, December 23, 2016

Galapagos Updates Cystic Fibrosis Program (6)

Prior updates on the progress of the Galapagos Cystic Fibrosis programs can be found below.
Galapagos Updates Cystic Fibrosis Program (5)
Galapagos Updates Cystic Fibrosis Program (4)
Galapagos Updates Cystic Fibrosis Program (3)
Galapagos Updates Cystic Fibrosis Program (2)
Galapagos Updates Cystic Fibrosis Program

Update (6)
Galapagos released phase 2, SAPHIRA(1) results this week with drug GLPG1837, for Cystic Fibrosis patients with the G551D mutation.  The link to the conference call is here

Some details from the conference call:
  • The company reported similar ppFEV1, in comparison to FDA approved Kalydeco
  • Kalydeco patients at baseline had a sweat chloride reading of around 45 mmol/L
  • After the seven day washout period, the sweat chloride level increased to a mean value of 98 mmol/L*
  • After 28 days, and dosing up to 500 mg GLPG1837 twice daily, sweat chloride fell to 66 mmol/L
  • For patients who exceeded the predicted target concentration, sweat chloride changed from a mean 94 mmol/L to 52 mmol/L
  • Sweat chloride did not fall to the original baseline Kalydeco level, of around 45 mmol/L
  • GLPG1837 was mentioned as being dose limited up to 600 mg twice daily
* The concentration of chloride in sweat is elevated in individuals with CF.

Thank you for reading.


Friday, December 16, 2016

CTP-543 Phase 1 Top-Line Results

Concert Pharmaceuticals announced top-line results this week for CTP-543.  The single and multiple ascending dose study was well-tolerated across all dose groups.  The company is planning on testing four doses (4, 8, 12, and 16 mg BID) in the phase 2 clinical trial scheduled to begin early 2017.  The phase 2 clinical trial will enroll around 100 patients with moderate to severe alopecia areata, with six month readout by the end of 2017.  Thank you for reading.

SAGE-217 Patent Issued

SAGE-217 was issued patent number US 9,512,165 B2, which runs into 2033.  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.


Tuesday, December 6, 2016

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,
Thank you for reading.

Friday, December 2, 2016

CTP-656 Clinical Trial Initiated

CTP-656 for cystic fibrosis patients with CFTR gating mutations is now loaded in the website here NCT02971839.  The phase 2 trial is expected to start enrollment in January of 2017 to avoid the busy holiday season approaching.  The readout completion date is by the end of 2017.  Sweat chloride will be the primary endpoint of the study with FEV1 secondary.  With only 6-8 patients in each arm, the trial is not specifically powered for efficacy, but more likely to compare the three different dosages, and decide which one will be taken further into a phase 3 clinical trial, where FEV1 will be the primary endpoint.

Estimated Enrollment:40
Study Start Date:January 2017
Estimated Primary Completion Date:December 2017 (Final data collection date for primary outcome measure)
ArmsAssigned Interventions
Experimental: CTP-656, Dose 1, QD
Oral tablet dosed once-daily for 28 days
Drug: CTP-656, Dose 1 (QD)
Experimental: CTP-656, Dose 2, QD
Oral tablet dosed once-daily for 28 days
Drug: CTP-656, Dose 2 (QD)
Experimental: CTP-656, Dose 3, QD
Oral tablet dosed once-daily for 28 days
Drug: CTP-656, Dose 3 (QD)
Active Comparator: Kalydeco, 150 mg Tablet (open label)
150 mg, oral tablet dosed twice-daily for 28 days
Drug: Kalydeco, 150 mg Tablet (BID; open-label)
Placebo Comparator: Placebo, Oral Tablet, QD
Oral tablet dosed once-daily for 28 days
Drug: Placebo (QD)

Detailed Description:
This is a randomized, parallel-group, double-blind, placebo controlled multicenter study to evaluate the safety and efficacy of CTP-656 in CF patients with CFTR gating mutations, compared to Kalydeco, for a total of 28 days. Subjects will be randomized to receive either double-blind CTP-656 or placebo, or open-label Kalydeco.

Friday, November 25, 2016

Janus Kinase (JAK) Inhibitors

Janus Kinase Inhibitors - JAK's have shown to be successful in a variety of different disease indications.  The science of these inhibitors is still in the early stages of understanding.   They operate by inhibiting one or more of the family of enzymes, (JAK1, JAK2, JAK3, TYK2), and interfering with the signaling pathway.  They have shown to be successful in cancer and inflammatory diseases to date.  Concert Pharmaceuticals currently owns patents for the following three deuterated JAK inhibitors, with indications that each has shown to be effective in, prior to the company adding deuterium to the entity.

Selectivity: JAK1,2 
Indication:  Myelofibrosis, Polycythemia Vera, Alopecia Areata  
Patent: 2032 US

Selectivity: JAK1,2, TYK2
Indication: Rheumatoid Arthritis, Psoriasis
Patent: 2032 US

Selectivity:  JAK1,2
Patent: 2033 US

The non-deuterated versions of these JAK's have already shown proof-of-concept (POC), essentially reducing the risk for Concert to bring the drugs to market, for other or same, previously tested indications.  It's rare to have a full runway of patent years ahead, with clinically tested drugs, at your disposal.  We'll follow the Janus Kinase landscape with any new findings in the future.  Thank you for reading. 


Friday, November 18, 2016

CTP-543 Alopecia Areata Market Opportunity

Concert Pharmaceuticals will be entering a phase 2 clinical trial with CTP-543, for the indication of moderate to severe alopecia areata, in the first quarter of 2017.  Proof-of-concept (POC), has already been indicated in a small phase 2 academic study by Columbia University with results of the auto-immune disease here JCI.  We are estimating total revenue that CTP-543 could achieve if FDA approved for alopecia areata, based on some recent Dermatologic Drug Prices.

Up to 650,000 affected with alopecia areata U.S. any given time (Concert literature)
30% to 50% may have moderate to severe (195,000 to 325,000) US
Mid range population moderate to severe = 260,000 US
Market capture rate of 25% = 65,000 US moderate to severe
Price per tablet once daily = $23.33 or $700 per month

Peak revenue estimate $700 x 12 x 65,000 = $546 million

Risks to Assessment
Revenue split with another equally effective drug
The pool of potential patients is too high
Market capture rate of 25% too high 
$700 monthly, or $23.33 per tablet
Insurance does not cover the indication

Please feel free to comment, to add any information I may have missed.  Thank you for reading. 


Friday, November 11, 2016

STAT3 Phosphorylation with CTP-543

Concert Pharmaceuticals is currently running a phase 1 pharmacodynamics (PD) clinical trial, before heading into a phase 2 clinical trial for patients with moderate to severe Alopecia Areata.  The goal of the (PD) part of the phase 1 trial, will test CTP-543's ability to affect downstream gene regulation similar to ruxolitinib, with results in Q1 2017.  Ruxolitinib which is already an FDA approved drug for various cancer indications has been tested for it's ability to affect downstream gene regulation STAT3.  The results for ruxolitinib are below, and which can also be found in this link JAKAVI-ruxolitinib. 

Ruxolitinib inhibits cytokine induced STAT3 phosphorylation in whole blood from healthy subjects and MF patients.  Jakafi administration resulted in maximal inhibition of STAT3 phosphorylation 2 hours after dosing which returned to near baseline by 8 hours in both healthy subjects and myelofibrosis patients.

In vitro studies indicate that CYP3A4 is the major enzyme responsible for metabolism of ruxolitinib.  Parent compound is the predominate entity in humans representing 60% of the drug-related material in circulation.  The two major and active metabolites were identified in plasma of healthy subjects representing 25% and 11% of parent AUC.  These metabolites have one-half to one-fifth of the parent JAK-related pharmacological activity.  The sum of all active metabolites contribute to 18% of the overall pharmacodynamics of ruxolitinib.  

Bottom Line:  CTP-543 will be compared to the above ruxolitinib data, after completion of the current phase 1 clinical trial.  The drug will be advancing into a phase 2 clinical trial for patients with moderate to severe Alopecia Areata, in the first quarter of 2017.  CTP-543 is the deuterated version of ruxolitinib.  Thank you for reading.