New Antidepressant Botanical Drug (BLI-1005) (Original code name : 1421)
Target Indication
BL1005 is extracted from an herb used as sedative in Traditional Chinese Medicine (TCM). BLI-1005 exerts its antidepressant effects by inhibiting the reuptake of norepinephrine by the norepinephrine transporter. We therefore develop BLI-1005 as a treatment for Major Depressive Disorder (MDD).
Drug Type
New drug category: Botanical new drug
Formulation: Oral capsule
Foresight and Global Development
Patients with depression usually show symptoms such as unhappiness, lack of interest, lack of appetite, change in sleeping habits, inability to concentrate, negative thoughts, or even lack of interests in life. These symptoms usually last for more than two weeks and affect daily life of patients.
The causes of depression include genetics, trauma, stress, etc. Other psychotic diseases or substance abuse may also result in comorbidity with depression. According to WHO, there are approximately 350 million people suffering from depression. Among those who committed suicide, 87% reached the severity of Major Depressive Disorder (MDD). As a result, MDD had been classified as one of the top three diseases of the 21st Century by WHO. Unfortunately, there are still great unmet needs for effective MDD treatments.
Current antidepressants are only effective for 50% of the patients, and the high recurrence rate remains a problem for clinical treatments. Hence, several new drugs are currently under development. The global antidepressants market has reached US$ 20.3 billion in 2009, and the market size is expected to grow continuously.
Result
1. Inhibition of TBZ-induced hypothermia in mice
BLI-1005 has shown the ability to inhibit TBZ-induced hypothermia, an index of anti-depressive effect.
Treatment
Route
Dose (mg/kg)
% Inhibition of Body Temperature
60 min
90 min
120 min
BLI-1005
PO
10
5
0
0
PO
30
30
33
27
PO
100
55*
59*
63*
PO
300
77*
74*
80*
Imipramine
PO
3
89*
84*
83*
* The inhibition of TBZ-induced hypothermic response is 50 percent or more, which is considered
a threshold for significant antidepressant effect in this assay.
2. In-vitro radioligand-binding assay
BLI-1005 possesses the activity of inhibiting norepinephrine transporter, a mechanism of how antidepressants work.
Assay name
Concentration of BLI-1005
% of Inhibition
IC50
Norepinephrine Transporter
0.3 μg/mL
20
2.102 μg/mL
1 μg/mL
34
3 μg/mL
60
10 μg/mL
76
30 μg/mL
84
Repeated dose 28-day subacute oral toxicity studies have demonstrated that NOAEL (no-observed adverse effect level) of BLI-1005 is 3000 mg/kg/day for both dogs and rats.
Phase I study completed has also proved that there is no safety concern for single dose BLI-1005 oral administration.
According to the report of phase I study, the conclusion can be drawn as followed. No subject had serious adverse event and no subject discontinued due to adverse event; no clinically significant findings in physical examinations, vital signs, electrocardiogram, laboratory measurements and C-SSRS was observed throughout the treatment period; the oral administration of BLI-1005 in healthy volunteers was safe and well-tolerated with dosages ranging from 380 mg to 3800 mg.
Product Advantage
As a biotanical extract, the safety of BLI-1005 has been demonstrated in the phase I clinical phase.
BLI-1005 demonstrated antidepressant effects in animal studies. Working as a mechanism of Norepinephrine reuptake inhibitor, BLI-1005 may fulfill the needs for effective MDD treatment which are not satisfied by current SSRIs- and SNRIs- based medication.
BLI-1005 is covered by 11 patents in 8 countries as the US, United Kingdom, Japan, Germany, France, Italy, Switzerland and Taiwan.
Research and Development Stage
Phase I study was completed and it supported that there is no safety concerns of BLI-1005 in human up to 3800 mg single dose.
A phase II human clinical trial was initiated in 2015.
Grants and Recognitions
2013 Selected as a model case by Center for Drug Evaluation, Taiwan.
2012 Subvention for R&D granted by Industrial Technology Development Program, Ministry of Economic Affairs.
2012 Approved as part of the “Cross-Strait Cooperative Pharmaceutical R&D Pilot Project Plan.”
2012 Received recognition from Ministry of Health and Welfare as a new biopharmaceutical.
