Allergan says yes to CNS (central nervous system) and NMDA (N-methyl-D-aspartate) modulating drugs for depression, with the purchase of private company Naurex for $560 million. We previously wrote about NMDA drugs and Naurex here, NMDA Receptor Modulators. NMDA drugs are rapidly gaining press as mono and adjunct therapy for depression patients. Avanir is currently in a phase 2 clinical trial with their NMDA modulator AVP-786, as an adjunctive therapy in patients with Major Depressive Disorder, with an inadequate response to anti depressant treatment. Avanir will complete their phase 2 clinical trial in the first half of 2016. Naurex has already tested NRX-1074 as an IV as adjunctive in a phase 2 study for patients with Major Depressive Disorder. Next, the company will test an oral NRX-1074 in a planned phase 2 clinical trial as mono-therapy for Major Depressive Disorder (MDD).
Bottom Line: At this point we have no idea how NRX-1074 oral will perform, compared to their completed intravenous phase 2 clinical trial for patients with Major Depressive Disorder (MDD). Avanir with drug AVP-786, is most likely two years ahead of NRX-1074 in the clinical trial process. Thank you for reading.
We originally wrote about CTP-730 here, What is CTP-730. Today Celgene held it's second quarter conference call this morning. This is what Scott Smith head of Global Inflammation and Immunology had to say regarding the launch of Otezla, and the future pipeline of indications that Otezla could potentially get approved for.
Scott Smith President, Global Inflammation and Immunology
"Thank you, Jackie. Q2 was a great quarter for Celgene I and I. During the quarter, we saw significant acceleration of prescriptions and revenues for OTEZLA in the U.S. and strong initial uptake in the early launch countries internationally. We also made progress on indication expansion for OTEZLA advancing a global Phase III program in Behcet's Disease and Phase II studies in atopic dermatitis and ulcerative colitis.
Now turning to OTEZLA, were seeing a substantive uptick in revenues and demand in the U.S. Total prescriptions far outpace the recent launch analogs in the I & I space and currently measure over 4,500 TRx' per week based on the latest data. Revenues for the quarter grew to $90 million worldwide and we're tracking well in line with internal plans. We're very encouraged at the progress we're seeing outside of the U.S., both in Canada and in early launch countries in the EU. After only five months, we're outpacing all recent launches in Germany. Still very early in the launch, but this initial success helps reinforce the global value proposition of OTEZLA and the need for novel approaches to the treatment of I & I disease.
The trends in the U.S. are supported by positive launch metrics. While the PSA launch continues to make strong and steady progress, the launch of psoriasis indication has fueled much of the recent acceleration.
Access to new therapies is a critical component of success in the market. And it's important to note that over 70% of OTEZLA prescriptions in pre-biologic patients are being approved on first pass. Total U.S. patient share for OTEZLA in psoriasis surpassed ALLERA some months ago and passed ENBREL's overall patient share in June. The source of business in psoriasis continues to be heavily weghted towards the pre-biologic sector with 75% of patients coming to OTEZLA from topical therapy or no therapy at all over the past 12 months".
Bottom Line: CTP-730 is Concert Pharmaceutical's deutered enhanced Otezla, that just finished a phase 1 clinical trial. CTP-730 has been licensed to Celgene, with future milestone, and royalty payment potential for Concert. Otezla has had a very strong launch, and could expand into Behcet's Disease, atopic dermatitis, and ulcerative colitis. Thank you for reading.
There is not an FDA approved drug for the treatment of agitation in patients with dementia of the Alzheimer's type. Otsuka Pharmaceuticals has a total of five phase 3 clinical trials that have been in progress, or about to start. The two drugs that are addressing this indication are Rexulti (Brexpiprazole), and AVP-923 (AVP-786). Rexulti is a joint 50% ownership between Lundbeck and Otsuka. AVP-923 (AVP-786) is 100% owned by Otsuka, with a milestone and royalty licensing agreement with Concert Pharmaceuticals. The side effect comparison between Rexulti and AVP-923 is below.
Rexulti (Brexpiprazole)
In clinical trials here phase 3 Schizophrenia, the 2 mg group of Rexulti exhibited the following side effect profile.
Insomnia 13.4%
Headache 9.3%
Agitation 8.6%
In clinical trials here phase 3 Adjunctive Major Depression, the 2 mg group of Rexulti exhibited the following side effect profile.
Weight Increase 8.0%
Akathisia 7.4%
AVP-923 (AVP-786)
In a phase 2 clinical trial for patients with agitation of the Alzheimer's type, the following side effect profile was exhibited.
Falls 8.6%
Diarrhea 5.9%
Urinary Tract Infection 5.3%
Falls had a baseline skew, that had more patients in the treatment group (17.2% to 12.6%) and 25% more patient-day exposure to AVP-923 than placebo, noted here JAMA DM/Q Phase 2 Alz. Agitation. In addition from that phase 2 clinical trial, there were no new cardiovascular safety signals and no clinically significant changes in QTc observed in the study. These results above are consistent with several other clinical trials that Avanir has run with AVP-923, for traumatic brain injury, or stroke here Prism II, with diarrhea being the most commonly reported adverse event.
Bottom Line: Otsuka has advanced the deutered version of AVP-923, (known as AVP-786) into three phase 3 clinical trials for the treatment of agitation in patients with dementia of the Alzheimer's type, to begin soon. The company also has two ongoing clinical trials in progress with Rexulti for the same patients, that started in 2013. The patent for Rexulti runs until 2027 US and until 2025 EU, the patent for AVP-786 runs until 2030 in the US, and 2028 in the EU. Thank you for reading.
Late Friday the FDA approved Otsuka and Lundbeck's atypical antipsychotic drug Rexulti (Brexpiprazole), as mono therapy for Acute Schizophrenia, and as adjunct therapy for Major Depressive Disorder. We previously wrote about Brexpiprazole here Lundbeck Clinical Trials Update . Otsuka, the maker of Abilify has been under pressure to replace lost sales of the world's number one selling drug Abilify (Top Selling Drugs) in 2014, due to patent expiration in 2015. Rexulti (Brexpiprazole) has been the drug to replace Abilify for several similar CNS indications. Under the marketing agreement Lundbeck (co-developer and co-commercialization) will get 45% of Brexpiprazole U.S. net sales, and 50% net sales in Europe. The patent for Rexulti runs until 2027 US, and 2025 in the EU. The label for Rexulti is below.
INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI ®(brexpiprazole)
INDICATIONS
REXULTI is indicated for:
- Use as an adjunctive therapy to antidepressants in adults with major depressive disorder
- Treatment of schizophrenia in adults
IMPORTANT SAFETY INFORMATION
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.
Rexulti (Brexpiprazole) deemed the second generation Abilify, is getting a similar safety label as Abilify, even though the side effect profile between the two drugs varies, with Rexulti showing improvement in some areas such as akathisia. It will be interesting to see what kind of label AVP-786 gets for the Treatment of Agitation in Patients with Dementia of the Alzheimer's Type. AVP-786 is about to enter phase 3 clinical trials in September. Thank you for reading.
Today the FDA approved the combination of Vertex's Lumacaftor and Kalydeco (Orkambi) for cystic fibrosis people, 12 years and older, with two copies (homozygous) of the F508del mutation. We originally wrote about Orkambi here Vertex Pharmaceutical Passes Advisory Committee, when they were front and center with the FDA advisory committee.
Orkambi has been appoved for CF patients despite the relatively small improvement in FEV1 in two F508del clinical studies. How high is the bar set for other companies to get clinically significant improvement over Kalydeco as mono therapy for the G551D mutation, and Orkambi combination therapy, for patients 12 years and older, with two copies of the F508del mutation?
G551D Through 24 weeks Kalydeco 150 mg q12h
- 10.6% and 12.5% FEV1 improvement vs. placebo
G551D Through 48 weeks Kalydeco 150 mg q12h
- 10.5% and 10.0% FEV1 improvement vs. placebo
- 3,000 Worldwide Patients
F508del Through 24 weeks 2 tablets (ivacaftor 125 mg / lumacaftor 200 mg) q12h
- 2.6% and 3.0% FEV1 improvement vs. placebo
- 26,000 U.S. + EU Orkambi Patient Potential
These are the FEV1 (forced expired volume) numbers that other companies will be considering as significant, to improve current therapy for CF patients. The side effect profile was mild, as a high percentage of patients completed the Vertex clinical trials. The annual wholesale acquisition cost (WAC) will be priced at around $259,000 per patient for the Orkambi combination. Thank you for reading.
