Thursday, April 28, 2016

CTP-656 Multiple Ascending Dose Study

Concert just completed a phase 1, multiple ascending dose study of CTP-656, with placebo.  Some additional value can be found in the following press release from Concert regarding this study. Multiple Ascending Dose Phase 1.

Pharmacokinetics:  "Across all doses, the average plasma half-life of CTP-656 was approximately 18 hours at steady state.  CTP-656 showed a dose-proportional increase in exposure with repeated dosing for the 75 mg and 150 mg doses. The 225 mg dose group showed higher than dose-proportional exposure."

CTP-656 in the previous phase 1 oral solution trial, showed a half-life around 15 hours.  So it looks like an improvement was seen with the solid dosing of CTP-656 over a seven day study, as it pertains to half-life.  CTP-656 was well-tolerated and it's safety profile was comparable to that of Kalydeco. 

Also within the press release "We are pleased to see that full bioavalability of CTP-656 was retained even with a low fat meal," stated Dr. Cassella. 

Additional interest is that the company has announced that they will be participating in 39th European Cystic Fibrosis Conference being held June 8-11, 2016 in Basal Switzerland.  Thank you for reading.

Sunday, April 24, 2016

Inter Partes Review and Drug Patents

There is an important case (Couzzo Speed Technologies V. Lee) scheduled for Monday April 25th, regarding a prior Inter Partes Review IPR, and a subsequent challenge to that outcome, which will be heard in the Supreme Court.  The patent in question has nothing to do with drugs, but an important precedent may be set with the case result.  The questions to be addressed:
1.  May the patent trial and appeal board apply the broadest reasonable interpretation of patent claims during an inter partes review hearing?
2.  Is the patent trial and appeal use of inter partes review judicially reviewable?

Companies such as Auspex, and Concert Pharmaceuticals, both which have a broad pipeline of deuterated patented drugs, may benefit from the inter partes review process, as a way to resolve potential patent issues should one occur.  An IPR, is intended to be quicker, more efficient, and less expensive for post-grant patent challenges.  Thank you for reading.

 

Wednesday, April 13, 2016

NMDA Receptor Modulators for CNS Disorders

We originally wrote about this topic here NMDA Receptor Modulators for Depression. There are now several companies interested in bringing a variety of NMDA drugs into the clinic, either as mono-therapy or coupled with enhancers.  Let's have a look at some of the companies, their drug, and indications that they are targeting.

Avanir:  Otsuka
AVP-786  Dextromethorphan + Quinidine
Ph 3  Agitation in Alzheimer's Disease
Ph 2  Residual Schizophrenia
Ph 2  Major depressive disorder (adjunct)

Axsome: AXSM
AXS-05  Dextromethorphan + Bupropion  
Ph 3 Treatment resistant depression
Ph 1 Agitation in Alzheimer's Disease

Cerecor:  CERC
CERC-301  NR2B Specific NMDA antagonist oral
Ph 2 Major depressive disorder (adjunct)

JNJ / Janssen
Esketamine  intranasal
Phase 3 adjunct with anti-depressant for TRD

Naurex:  Allergan
NMDA receptor partial agonist with selective properties
Ph 2 NRX-1074  IV
Ph 1 NRX-1074 Oral
Ph 3 GLYX-13 (Rapastinel) Weekly IV Major Depressive disorder

Vistagen:  VSTA
AV-101  NMDA selective antagonist oral
Ph 2 AV-101 Major depressive disorder 

Over the next couple years, we should see some meaningful clinical readouts from some of these companies.  Potentially NMDA drugs may provide for a more efficacious and safer, sustainable therapy, aside from current antidepressants for some of the above indications. Thank you for reading.

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Friday, April 1, 2016

Nuplazid: FDA Safety Label

Acadia Pharmaceutical's completed their advisory committee meeting (ADCOM) on March 29th.  After receiving a positive review from the committee, the next issue to be determined will be the box safety labeling.  Below is wording from the FDA Briefing Documents.

This sample of patients compared to their appropriate control group demonstrates more than double the risk of serious adverse events (SAE) in the PDP6 trial population (Observed Risk of death or SAE is 2.38 times greater [95% CI 1.00 to 5.73, p=0.05]) for 34 mg Pimavanserin vs. placebo.

Let's have a look at a mortality black box label that many of the anti-psychotics currently carry, including the newly approved Rexulti (brexpiprazole) for Acute Schizophrenia and as adjunct for Major Depression Disorder. 

Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death compared to placebo (4.5% vs 2.6%, respectively). Although the causes of death were varied, most of the deaths appeared to be cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

I think the above is a likely label scenario for Nuplazid.  In addition, the FDA may advise Acadia to run a phase 4 confirmatory clinical trial as part of approval.  

Bottom Line:  Acadia has completed some nice pre-marketing research for Nuplazid, and found that a black box warning label was not high on the list of doctors when deciding whether or not to prescribe this drug.  In other words, they would still prescribe the drug, as the best alternative for an unmet need regardless of the safety label, as Nuplazid has shown in clinical trials to not contribute to motor impairment.   May 1st, is the scheduled day that the FDA should approve the drug.  Thank you for reading.