Botanical Drugs—Farmaceuticals vs. Pharmaceuticals
The U.S. Food and Drug Administration (FDA) has recently established a Botanical Drug Team as well as a set of guidelines for the development of heterogenous botanicals as ethical pharmaceuticals with disease-related claims (the EMEA also has developed a similar parallel set of guidelines for the EU). Such changes in the FDA regulatory environment now allow for the development of botanicals at a much more rapid pace than new chemical entities or biologics, resulting in approval costs that may be reduced by an order of magnitude. Additionally, this new guidance provides for unique guarantees of market exclusivity for NDA botanicals as well as the acceptance of synergistic combinations of bioactives.
The synergistic components found in botanical mixtures represent a largely untapped source of new pharmaceutical products with novel and multiple mechanisms of action. Recent developments in plant biotechnology have created the tools to produce botanical mixtures at a level comparable to that of pure drug compounds, thus meeting the requirements of the FDA.
Botanical drug products will ultimately compete along side conventional pharmaceuticals in the $300 billion global pharmaceutical marketplace.
Botanical Drugs in Development
PMI-001—For Auto-immune Diseases
PMI-001 is a novel, orally bioavailable, multi-mechanism botanical drug for auto-immune diseases. Protected by six issued patents, PMI-001 exerts its potent anti-inflammatory / immunosuppressant activities through unique and synergistic modes of action including inhibition of IL-2, a-TNF, i-NOS, and COX-2 gene transcription. PMI-001 has currently completed a six month, double-blind, Phase II clinical trial in 120 patients with moderate to severe rheumatoid arthritis, at 12 centers throughout the U.S. The results of this trial showed exceptional stand-alone ACR efficacy results rivaling combination biologics drug regimens, a mild side effects profile, radiographic data showing halting joint erosion and narrowing at six months, and evidence of extremely rapid pain and inflammation reduction (ACR70 as early as 2 weeks). Phase III development plans have commenced.
PMI-002—A multi-functional adjuvant chemotherapeutic / anti-inflammatory / anti-tissue degenerative agent
PMI-002 is a novel and proprietary botanical drug formulation possessing a variety of anti-neoplastic activities including: 1) selective induction of apoptosis in a variety of tumor types, including colon, prostate, and lung, via induction of both stress activated proteins such as c-Jun N-terminal kinase, and extracellular signal-regulated kinases, 2) inhibition of P-glycoprotein and multidrug-resistance protein 1 (MRP1) mediated transport, 3) blockade of malignant cell transformation, and 4) modulation of Phase I and Phase II xenobiotic metabolizing enzymes that detoxify a wide range of carcinogens. Animal models have recently confirmed the ability of PMI-002 to substantially reduce tumor load in both colon cancer and non-small cell lung cancer (NSCLC) xenograph models. Also, additional complementary bioactivities of PMI-002 have recently been discovered related to its ability to inhibit a range of pro-inflammatory cytokines, as well as potentially prevent both neurological and opthalamic degenerative disorders.
Botanical Drug Development Candidates in Early Discovery
Investment in proprietary discovery technologies and their resourceful implementation has produced an extensive pipeline of botanical drug candidates at various stages of development. Some of these select candidates include:
- PMI-004—advanced botanical formulation for type II diabetes - Represents a multi-mechanism bioactive that: 1) in adipocytes increases adiponectin secretion, 2) in the liver lowers PEPCK expression, and 3) in muscle cells increases cellular signaling through the insulin receptor pathway, increasing glucose uptake, glycogen synthase, and glycogen accumulation.
- PMI-005—botanical bioactive, derived from a common vegetable, that inhibits gene expression of a variety of pro-inflammatory cytokines (including a-TNF, i-NOS, IL-1b, and COX-2). Currently undergoing a human clinical trial in osteoarthritis. Also may have utility in the management of severe / life threatening inflammatory conditions, such as in the management of the septic patient.
- PMI-006—botanical bioactive, derived from a spice, that inhibits a range of inflammation-related enzymes (including a-TNF and COX-2). Also possesses range of novel bioactivities related to both lipid and glucose metabolism (RXR receptors).
- PMI-007—a powerful, centrally acting, botanical appetite suppressor which acts via a unique central pathway in the nutrient-sensing hypothalamic neurons by increasing ATP content / production. It possesses potent anorectic activity without typical CNS appetite suppressor side effects. Pre-clinical data has shown that the agent suppresses both appetite and reduces weight in animal models, while there is supporting clinical evidence of human efficacy.
- PMI-008—botanical bioactive, derived from an agricultural waste processing stream, that blocks fat accumulation/absorption and promotes weight loss via interaction with a variety of lipases including PL, LPL, and HSL.
- PMI-016—a powerful, plant-derived anabolic / ergogenic agent, with no androgenic side effects; could be used in a range of human muscle wasting disorders, including those associated with both cancer and AIDS, as well as general aging (sarcopenia). This agent has been shown to induce protein synthesis in muscle cells (similar to IGF) and promote a reduction in protein degradation, while it has also been shown to increase growth hormone gene transcription and decrease in ubiquitin protein ligase gene transcription. PMI-016 shows no binding to testosterone receptor in contrast to anabolic steroids.