ABVC Biopharma, based in California, has programs in Phase II trials to treat major depressive disorder, adult attention deficit hyperactivity disorder and myelodysplastic syndrome.
Botanical medicines – plants – have formed the bulwark of medicine since time immemorial, but took a back seat to faster-acting, more robust synthesized compounds during the late 19th and 20th centuries. Botanicals are still used by much of the world, however, and are the basis of many new and emerging therapeutics.
ABVC Biopharma, based in California, has programs in Phase II trials to treat major depressive disorder (MDD), adult attention deficit hyperactivity disorder (ADHD) and myelodysplastic syndrome (MDS) using active herbal ingredients derived from traditional Chinese medicines. BioSpace caught up with ABVC Biopharma’s CEO, Howard Doong, M.D., Ph.D., to discuss the company’s work in botanicals.
BioSpace (BSp): Why are botanicals experiencing a resurgence of interest?
Howard Doong (HD): During the past several decades, western researchers have gradually begun to look east to find new medicines to effectively address some of our most intractable diseases.
Very often, researchers experiment with botanical drugs because they are generally biocompatible and biodegradable, very safe to use, and patients usually do not develop drug resistance, which happens with many synthetic drugs. For example, chloroquine phosphate is one of the most commonly used synthetic antimalarial drugs. What if a patient develops resistance to this synthetic drug? Try another synthetic compound? No, researchers have found that when botanical drugs derived from the dried leaves of the artemesia plant were given to malaria patients who failed standard drug therapy, all fully recovered after five days.
Researchers also have learned in the past several decades that a single compound of a synthesized drug sometimes may not be effective in treating certain diseases if it just acts alone. Botanical drugs, on the other hand, are already complex mixtures and may work together to generate a synergistic effect.
Presently, there are more than 500 pending applications at the FDA for medicines derived from plants. The interest stems from their better safety profile, fewer side-effects and lengthy human experience, as wel as a desire to address the strong Asia market, where herbal medicines remain widely used.
BSp: How are biologics different from traditional Chinese medicine?
HD: Traditional Chinese medicine (TCM) usually involves minimal alteration of the roots, flowers, stems and leaves of the plant, which are then combined with a tea or broth for consumption. Today’s botanical medicines use active pharmaceutical ingredients that are extracted and concentrated from plants. Any unwanted ingredients or compounds in the plants are removed during the production process.
BSp: What’s in your pipeline?
HD: Our product pipeline consists of a medical device, central nervous system (CNS) drugs and oncology drugs:
- Vitargus® (ABV-1701) is an injectable, in situ-forming hydrogel designed to be used to treat retinal detachment after retina repair surgery. It is defined as a medical device, not a therapeutic drug. After retinal reattachment, the patient does not require face-down positioning.
First in human trials showed an immediate improvement in visual acuity after surgery. It allowed patients to have unrestricted movement and required no post-operative fluid removal because Vitargus is completely biodegradable. A Phase II clinical trial will start in early 2022 with sites in Australia and Thailand.
In December 2021, Vitargus® received the National Innovation and Renewal of Diligence award from the Institute for Biotechnology and Medicine Industry of Taiwan.
- In CNS, ABV-1504 is a single-herb botanical drug that is extracted from the dry root of Polygala tenuifolia Willd. Known as yuanzhi, this is a traditional Chinese medicine for the treatment for major depressive disorder (MDD).
At six weeks, a Phase II trial showed a 52% response rate versus 35% for placebo and a 13.2-point mean change from baseline using the Montgomery-Åsberg Depression Rating Scale (MADRS). In contrast, fluoxetine (Prozac®) caused an 8.8-point mean change from baseline. Administered in capsule form, ABV-1504 is stable at room temperature for at least 36 months.
We recently completed a draft of the Phase III study protocol and will be entering into licensing discussions with big pharma companies that have been following the progress of ABV-1504. We expect a Phase III trial will be conducted as a collaboration between ABVC and our license partner(s). The timetable will be determined as a result of those discussions.
- ABV-1505 is being developed to treat attention deficit hyperactivity disorder (ADHD), also using the active ingredient found in P. Tenuifolia Willd. It works as a selective norepinephrine reupdate inhibitor (NET) and has completed a Phase II trial.
Simply speaking, norepinephrine is a neurotransmitter. The more neurotransmitters are retained in the nervous system, the more nerve impulses can be transmitted. More nerve impulses have been shown to improve attention deficit and hyperactive symptoms, and permit more focus on a specific task.
- BV-1601, a Phase I clinical study for treating MDD in cancer is expected to be completed by the end of 2022. end of 2022.
- For oncology, we are developing ABV-1501 for triple negative breast cancer, ABV-1703 for pancreatic cancer and ABV-1702 for myelodysplastic syndrome. Each is in a Phase II clinical study.
The compounds are based upon Maitake BLEX-404, a botanical drug that is extracted from the fruit body of maitake mushrooms (Grifola frondose, also called Hen of the Woods). It is grown in northeastern Japan and in northeastern America.
A Phase I/II trial involving 34 breast cancer patients showed the patients were free of disease at the end of the trial and that the compound exhibited no dose-limiting effects. It appeared immunologically stimulatory, and measurable inhibitory effects were seen.
BSp: What’s next for ABVC Biopharma?
HD: This year ABVC will seek a Phase III partner to advance ABV-1504 for MDD. We also will start a self-funded pivotal trial Phase for Vitargus®, with a U.S. Food & Drug Administration premarket approval application (PMA) targeted for 2024. We expect funding to support additional Phase II trials for oncology and ADHD medications, as well as to add new indications to our pipeline.
