ITI-007 Phase 3 Results

This is the second phase 3 clinical trial for patients with schizophrenia and Intra-Cellular drug ITI-007.  This trial had Risperidone as an active comparator and a placebo arm, the clinical trial is here NCT02469155.  I am including our write up on the first phase 3 clinical trial (Study '301) here ITI-007 Phase 3 Results, for the specific reason of attempting to uncover how ITI-007 has performed on the PANSS Negative Symptoms subscale.  The first phase 3 clinical trial did not show statistically significant improvement in the PANSS Negative Symptoms subscale from the company PR in September of 2015. Below are the results for the ITI-302 phase 3 study.

• 60 mg -14.6
• 20 mg -15.0
• Risperidone 4mg -20.1
• Placebo -15.1

Today (Study '302) the company released phase 3 clinical trial top line results, that did not mention any significance to the Negative Symptoms in the Intra-Cellular press release. Intra-Cellular's ITI-007 results today should create some skepticism regarding the drug as a viable CNS candidate for Schizophrenia as Risperidone outperformed ITI-007.  The PANSS Negative Symptom subscale had zero mention from today's top-line press release. Based on the two phase 3 clinical trials, ITI-007 does not have a strong effect on the PANSS Negative Symptoms subscale.  AVP-786 is currently in clinical trials being tested for negative symptoms associated with schizophrenia.  Thank you for reading.           

Deuterated Drugs

Giving credit where due.  Below are two well written articles on the deuteration of drugs.  I have taken parts of the articles that seem pertinent to us, for investment purposes.  The complete articles can be accessed from the Concert Pharmaceuticals website below. 

http://www.concertpharma.com/news/in-the-news/

From: "A decades-old drug technology finally nears it's big breakthrough"

Should Teva get regulatory approval, it would open a market in the “many tens of billions of dollars,” said Roger Tung, whose company Concert Pharmaceuticals Inc. is also developing treatments with deuterium.  “It would show the breadth of possibilities,” Tung, the chief executive officer of Lexington, Massachusetts-based Concert, said in an interview. “Deuterium provides unique properties that cannot be attained in any other way.”

From: "Deuterium switcheroo breathes life into old drugs"

Even champions of deuterated drugs note there are plenty of pitfalls. Thomas Gant, scientific founder of the deuterated drug maker Auspex (he’s no longer with the company) and inventor of many deuterated drug candidates, including SD-809, says most synthetic chemists don’t have a good grasp of how chemical reactions operate in the presence of deuterated reagents or substrates.

“It is actually pretty surprising how many reactions that most chemists wouldn’t think would have an effect on the positions of hydrogens will actually cause quite a bit of randomization and dancing around of hydrogen radicals,” he says. “So you run these reactions expecting it to have no effect on your deuterated drug, and in fact, you can see a pretty dramatic effect in some instances. It’ll essentially spread the deuterium around the molecule” so you don’t have the original compound anymore.

As far as intellectual property is concerned, Gant says, it’s important to know the law. Deuterated compounds are considered new chemical entities and can be patented. But to get a patent, he explains, “you have to have actually done the chemistry, produced the deuterated compound, shown the spectra, shown deuterium incorporation rates, and shown biology to demonstrate a perceived benefit.”

It’s not unusual for pharmaceutical companies to include deuterated versions of original drugs in their boilerplate wording for patents. “This is something that companies routinely do to scare off people who don’t understand patents,” Gant says. “People think that the deuterated compounds have been covered. But they haven’t been covered because they haven’t been made and they haven’t been tested. So it might be written in the general description, but it doesn’t actually cover the application of deuterated compounds.  
Thank you for reading.
 

Nuplazid Launch Progression

The launch of Acadia Pharmaceuticals Nuplazid for Parkinson's Disease Psychosis (PDP), so far has been successful based on management conference call discussions. We previously wrote about the commercialization opportunity here, Nuplazid Priced at $23,400 / Year. 

 Chief commercial officer Terry Moore had this to say regarding the launch of Nuplazid, "One of the things I find interesting is we do have physicians report back to us that they are very pleased with what they are seeing in terms of efficacy. But what I find interesting is that they are reporting that the caregiver is reporting that they see the difference at home and that they are reporting that to the physician." 
 
Medicare Part D has it covered as 34/mg, taken as two 17/mg pills a day, for around $2,000 for a 30 day supply.  The annual price is similar to company guidance of $24K per year Nuplazid, for Parkinson's Disease Psychosis, which is the only approved drug for this unmet need. 

Bottom Line:  This market pullback may create a decent entry price for ACAD investors that have been waiting to go long the stock.  No positions in Acadia.  Thank you for reading.
 

D-Ibrutinib

A new patent for Concert Pharmaceuticals here, Deuterated Ibrutinib.  Ibrutinib is sold commercially under the name Imbruvica, and has a 50% - 50% sales sharing agreement by AbbVie and JNJ.  Imbruvica is a Bruton's tyrosine kinase (BTK) inhibitor for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, and is dosed once daily.  The patent expiration date is July 2032, for d-ibrutinib, and 2026 at the earliest for the non-deuterated ibrutinib. 

The drug is going head to head against Astra Zeneca's ACP-196, in a clinical trial below for previously treated subjects, with high risk chronic lymphocytic leukemia.

Estimated Enrollment:	500
Study Start Date:	June 2015
Estimated Primary Completion Date:	June 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ACP-196 ACP-196 will be orally administered until disease progression or unacceptable toxicity.	Drug: ACP-196
Active Comparator: ibrutinib Ibrutinib will be orally administered until disease progression or unacceptable toxicity.	Drug: ibrutinib

Bottom Line:  Analyst have projected up to 6 billion in annual revenue for Imbruvica, for various cancer indications.  The 500 patient head to head clinical trial against ACP-196 above will not readout until 2019, but more importantly when complete, will display a safety and efficacy comparison for these two drugs.  Thank you for reading.