AXS-05 Phase 3 Results for Alzheimer's Agitation

Axsome released phase 3 results today from their ongoing clinical trial evaluating AXS-05 for agitation associated with Alzheimer's disease. Currently there is no drug approved for this unmet need. The results below were good, with a rapid and substantial effect. The complete press release is at Axsome.com.

• Cohen Mansfield (CMAI) total score at 5 weeks, p=0.010 versus placebo
• Week 3 compared to placebo p=0.007
• Well tolerated and not associated with cognitive impairment or sedation

AXS-07 Phase 3 for Acute Migraine (Intercept)

This phase 3 clinical trial was called Intercept, the second phase 3 clinical trial completed after the Momentum phase 3 trial for patients experiencing an acute migraine. Below are the highlights of the successful trial, and the Intercept Phase 3.

• Pain Freedom 2 hours after dosing achieved by 32.6% of patients
• Pain Freedom at 24 hours after dosing in 22.7% of patients
• Freedom from most bothersome symptoms achieved in 43.9% of patients
• Rescue medication was used by 15.3% of patients at 24 hours

Based on these results, I expect the company to prepare and file an NDA (new drug application) prior to year end. Thank you for reading.

Market Correction

The S&P 500, has now sold off -29.84% from the all time high achieved just a month ago. The sell-off categorizes it in bear market territory. By looking at the chart below of the S&P 500, the support line from the 2018 December low is just a few percentage points lower, to the price of around 230. Let's see if that prior correction low of December 2018 provides support for this market.







AXS-07 Phase 3 Results for Acute Migraine (Momentum)

Axsome Therapeutics released phase 3 clinical data with AXS-07 for the treatment of acute migraine, for patients with an inadequate response to prior treatments.
The clinical trial met the two co-primary endpoints; Pain-Free at 2 hours after dose, and Absent most Bothersome Symptoms 2 hours after dose versus placebo. The clinical trial can be found here Momentum Phase 3. The trial also compared AXS-07 to Rizatriptan (a well known and effective generic drug for acute migraine) for these tough to treat patients, who have not responded to prior treatments. Comparisons below are AXS-07 versus Rizatriptan.

• Sustained pain freedom from 2 to 24 hours after dosing.  16.1% vs 11.2%  p=0.038
• Sustained pain relief from 2 to 24 hours after dosing.  53.3% vs 43.9%  p=0.006
• Sustained pain relief from 2 to 48 hours after dosing.  46.5% vs 36.5%  p=0.003
• Rescue medication was used for 23.0% of AXS-07 patients vs 34.7%  p=0.001
• Patient Global Impression of Change, AXS-07 vs Rizatriptan.                             p=0.022
• Return to normal function at 24 hours.                                                                      p=0.027

The clinical trial was a success, as AXS-07 above, compared well to the generic acute migraine drug Rizatriptan. The safety profile of AXS-o7 was similar to placebo. The company plans to file an NDA (new drug application) in the second half of 2020.

AXS-05 Phase 3 Results for MDD (GEMINI)

Axsome Therapeutics (AXSM) is higher today after releasing phase 3 results with AXS-05 for the indication of Major Depressive Disorder or (MDD). The press release is here, AXS-05 Achieves Primary Endpoint in Gemini Phase 3. Some major points from the outstanding results are as follows.

• AXS-05 at week 6 versus placebo  p=0.002
• Rate of remission of depression week 6 versus placebo  p=0.001
• Week 1 AXS-05 versus placebo p=0.007

All scores are based on the Montgomery-Asberg Depression Rating Scale or MADRS. The phase 3 clinical trial details can be found here NCT04019704. The company will file for FDA approval in the second half of 2020 for the indication of MDD, and potentially get approved for that indication in the first half of 2021. Below is the chart of the stock that appreciated +70% today.

AXS-12 Phase 2 Results for Narcolepsy

Axsome Therapeutics (AXSM) today, announced the results of their phase 2 clinical trial with drug AXS-12 (reboxetine) for Narcolepsy. The clinical trial is here clinicaltrials.gov. The trial results were better than anticipated. All comparisons of AXS-12 versus placebo were statistically significant.

• Reduction in Cataplexy attacks compared to placebo p=0.001
• Reduced daytime sleepiness compared to placebo p=0.003
• Improved cognitive function compared to placebo p=0.001
• Sleep quality and sleep related symptoms compared to placebo p=0.007

AXS-12 was safe and well tolerated.  Chart below.



Alopecia Areata Clinical Trial Comparison

Concert Pharmaceuticals, just released CTP-543 Phase 2 Results for patients with moderate to severe Alopecia Areata. The phase 2 results included the 12 mg cohort of the clinical trial, in addition to the already completed 8 mg results. Below are comparison's made with Pfizer's drug PFE-06651600 Phase 2 Alopecia Areata. As seen by the data below, Concert's CTP-543's 12 mg results are shown to be the most efficacious versus their own 8 mg arm, and against Pfizer's PFE-06651600 at 24 weeks. The SALT % Increase (mean) drop from baseline (CTP-543 SALT dropped- 50%), is on a percentage basis the largest SALT improvement of the three results below. Results below are relative improvement from baseline, not placebo adjusted.

• SALT Score of 100 = zero hair growth
• SALT Score of 0 = full hair growth 

The percentage drop of SALT score (hair growth improvement) is one of the tools used to evaluate the efficacy of different Alopecia clinical trial drugs. Next CTP-543 will be tested in two large phase 3 clinical trials, but that won't occur until around mid 2020. 
                                                                  

PFE-06651600
	Total (n=45) at 24 weeks
		Baseline	End of Treatment
SALT (mean)		88.1	54.5
SALT Increase (mean)		-33.6
SALT % Increase (mean)		0	38.1%
% SALT Reduction		% of 45 Patients Achieving Better SALT Scores
30%			47.9%
50%			37.5%
75%			27.0%
90%			25.0%
100%			12.5%
CTP-543 8mg
	Total (n=38) 24 weeks
		Baseline	End of Treatment
SALT (mean)		89.1	51.7
SALT Increase (mean)		-37.4
SALT % Increase (mean)		0	42.0%
% SALT Reduction		% of 38 Patients Achieving Better SALT Scores
30%			not measured
50%			47.0%
75%			29.0%
90%			16.0%
CTP-543 12mg
	Total (n=36) 24 weeks
		Baseline	End of Treatment
SALT (mean)		87.3	43.6
SALT Increase (mean)		-43.6
SALT % Increase (mean)		0	50.0%
% SALT Reduction		% of 36 Patients Achieving Better SALT Scores
30%			not measured
50%			58.0%
75%			42.0%
90%			36.0%

AXS-07 for Acute Migraine

Axsome’s AXS-07 is designed to treat acute episodes of migraine. The drug is a combination of Meloxicam and Rizatriptan. Rizatriptan belongs in a group called triptans which are oral drugs designed to treat moderate to severe migraine headaches. AXS-07 will also compete against a newer group of oral drugs known as CGPR inhibitors similar to Allergan's Ubrogepant. The recently announced news from Axsome, was that the company met with the FDA in May, and was told that the current phase 3 clinical trial for acute migraine AXS-07 Phase 3, if successful, would be the only clinical trial needed to file a new drug application (NDA).  The clinical trial is currently being run under a Special Protocol Assessment (SPA) which was granted by the FDA prior to the trial beginning. Axsome also announced that a 12-month safety study has commenced. Patients will roll off the current phase 3 clinical trial, and into the 12 month safety study, which is a standard requirement for a new drug application to be filed with the FDA. The company is expected to file for FDA approval in the second half of 2020, which could lead to approval in 2021. The patent for AXS-07 runs into 2036.  Thank you for reading. 

Smoking Cessation and AXS-05

A phase 2 Smoking Cessation trial with AXS-05 was completed in April of 2019 by Axsome Therapeutics and sponsor Duke University here Phase 2 Smoking Cessation. From the Axsome press release following results, a quote by James Davis of Duke University and principal investigator of the phase 2 clinical trial had the following to say.
"The findings in this trial are notable because AXS-05 was compared to bupropion, an approved treatment for smoking cessation," said James Davis, MD, Medical Director of the Duke Center for Smoking Cessation, and principal investigator of the trial. "The improvement of AXS-05 over bupropion observed in this trial is similar in magnitude to the improvement over placebo reported for the approved smoking cessation treatment varenicline in studies with a similar design. Reduction in ad-lib smoking was selected as the primary endpoint in this trial, because it has been shown to correlate with smoking abstinence. I look forward to the continued evaluation of AXS-05 as a smoking cessation treatment."
Varenicline is also known under commercialization as Chantix. The drug was developed by Pfizer, and FDA approved in 2006, with patent extending to 2020. After 2020 generic companies can replicate the drug and sell it at much lower prices. The drug has produced annual revenues of around $1 billion for Pfizer, even though the safety profile has come under scrutiny from the FDA. The side effect profile for Chantix is below. 
The most common side effects of CHANTIX include nausea (30%), sleep problems (trouble sleeping, vivid unusual strange dreams) constipation, gas, and/or vomiting.
The potential opportunity for Axsome Therapeutics with AXS-05, would be exhibiting similar efficacy as Chantix has in clinical trials, but with fewer side effects associated with treatment. Current chart below.

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AXS-05 and SAGE-217

Axsome and SAGE Therapeutics are in phase 3 development for two promising drugs that treat Major Depressive Disorder or MDD. Both companies have completed phase 2 clinical trials with very good results, and each have achieved the Breakthrough Therapy Designation (BTD) from the FDA. What's different from the current Selective Serotonin Reuptake Inhibitors or SSRI's, is that both AXS-05 and SAGE-217 are fast acting oral delivery drugs that show efficacy within days of treatment, compared to many weeks.
Let's see how AXS-05 and SAGE-217 compare in a side by side analysis of important facts to consider. From the file below, and from listening to company conference calls, both AXS-05 and SAGE-217 could get FDA approval and to commercialization around the same time in 2021. What stands out is that while SAGE Therapeutics currently sports an 8.49B market cap, Axsome Therapeutics just a 768M market cap. Thank you for reading.

Drug	AXS-05	SAGE-217
Action	NMDA	GABA
phase 2	ph 2 compare	ph 2 placebo
Remission wk 6	47%	45% *
BTD	√	√
Pivotal	√	√
phase 3 MDD	n= 300	n= 450
Start	6/1/2019	12/1/2018
End Expected	12/31/2019	12/31/2019
Safety Data Ext	n= 300	n= 600
NDA Filing est	6/1/2020	6/1/2020
Approval est	3/1/2021	3/1/2021
Delivery-oral	b.i.d.	qd
Patent	2034	2034
Market Cap	768M	8.49B
*15 day dosing

AXS-05 Path to Approval for MDD

• Axsome Therapeutics met with the FDA and was given an expedited pathway of AXS-05 for Major Depressive Disorder or MDD. Under this new agreement, the company's phase 2 clinical trial known as Ascend for MDD was given pivotal status, and will only need one other pivotal phase 3 with efficacy, to file a New Drug Application (NDA).
• The company plans to enroll for a new phase 3 placebo clinical trial in the 2nd quarter of 2019, with an expected completion date by the end of 2019. The company plans on initiating this phase 3 with an increased number of clinical sites recruiting participants, which will allow for completion faster over the successfully completed phase 2 Ascend clinical trial for MDD.
• The timeline for filing an NDA would then be in the first half of 2020. If this timeline holds up, AXS-05 could potentially get to commercialization around the same time as Sage Therapeutics drug SAGE-217, which is also pursuing the same MDD indication.

AXS-05 was given Breakthrough Therapy Designation (BTD) from the FDA for Major Depressive Disorder, and the patent extends out to 2034. Thank you for reading.

AVP-786 for Alzheimer's Agitation

Otsuka  Pharmaceutical announced results from the first phase 3 clinical trial TRIAD 1 & 2, for the treatment of Alzheimer's Agitation. The Otsuka press release from 3-25-19 is here AVP-786.  The results from that phase 3 were deemed to be significant for one of the two doses using the Cohen-Mansfield Agitation Inventory with the SPCD design. The other phase three clinical trials will utilize the more standard parallel group, placebo controlled design. The safety profile was similar to other clinical trials which included falls, urinary tract infection, headache and diarrhea. There will be a peered-reviewed journal with a more complete look of the results to follow.
The reported significant results become a positive for Concert Pharmaceuticals who could benefit from  a royalty agreement, should the drug achieve FDA approval. The patent for AVP-786 runs to 2030 in the U.S. Thank you for reading.