The novel coronavirus SARS-CoV-2 is affecting 65 countries and territories around the world with almost 90,000 reported cases and almost 3,000 deaths. This week, the WHO declared that it was too early to call the outbreak a pandemic but countries should be “in a phase of preparedness”. While there’s no proven treatment yet for the virus and the pneumonia it causes, there are more than 70 drugs or drug combinations potentially worth trying, according to the World Health Organization.
Among these candidates, the most promising seems to be Gilead Sciences’ SBECD-enabled remdesivir (GS-5734, originally developed against Ebola) which was highlighted in the New England Journal of Medicine for treating the first case of 2019 novel coronavirus in the United States. Gilead Sciences stated that while there were no antiviral data for remdesivir that show activity against 2019-nCoV at that time, there were available data in other coronaviruses. Remdesivir is not yet licensed or approved anywhere globally and has not been demonstrated to be safe or effective for any use.
Following the successful application of remdesivir in several hundred cases in China and the US, just his week Gilead announced the initiation of two Phase 3 clinical studies to evaluate the safety and efficacy of remdesivir in adults diagnosed with COVID-19 (the disease caused by the virus). These will enroll approximately 1,000 patients at medical centers primarily across Asian countries, as well as other countries globally at the beginning in March. The initiation of these studies follows the U.S. Food and Drug Administration’s (FDA) rapid review and acceptance of Gilead’s investigational new drug (IND) filing for remdesivir for the treatment of COVID-19. The new clinical studies expand the ongoing research into remdesivir, which includes two clinical trials in China’s Hubei province led by the China-Japan Friendship Hospital as well as the recently initiated clinical trial in the United States. Gilead has donated drug and provided scientific input for these studies, with results from those in China expected in April. “The speed with which remdesivir has moved into clinical development for this coronavirus reflects the pressing need for treatment options and the shared commitment of industry, governments, global health organizations and healthcare providers to respond to this public health threat with the highest urgency,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences.
How does CycloLab get into this picture?
CycloLab is a small private company located in Budapest, Hungary and is involved in the fight against coronavirus via its expertise in the cyclodextrin technology and by manufacturing the critical excipient, Dexolve (sulfobutyl-ether beta-cyclodextrin, SBECD) that enables remdesivir to work. SBECD is combined with a wide range of active pharmaceutical ingredients to improve their solubility or stability. Remdesivir, which is a broad-acting antiviral with tremendous efficacy, is practically insoluble in water, which prevents the preparation of an injectable formulation to treat patients. Once pharma companies (Gilead and numerous others globally) use the proper technology and combine the active with this particular cyclodextrin, remdesivir gets water-soluble, can exert its effect and fight the virus effectively.
The unexpected and sudden outbreak along with the quick spread of the disease and rapid increase of the cases draw a sudden need for SBECD globally. CycloLab is now making extra efforts and has started manufacturing campaigns with extra shifts to do its best in these troubled times. Since the beginning of January, we have been in discussion with multiple partners who are all involved in this fight with a common goal and established a strategy to support them in their trials and treatments. From Cyclolab’s perspective this technically means that we are manufacturing Dexolve with a forced march and make as much of the product in 4 weeks as we typically do in 3-4 months, which translates to the metric ton range. In the meantime, we are making efforts to even improve this support in case this is just the beginning and the situation gets worse. It should also be noted that these needs are mostly to cover the ongoing and upcoming clinical trials. Should the remdesivir get approved, the needs would definitely further increase and standardize on the long term. Of course, we cannot know what the future would bring, yet we are prepared to support this fight and are bending every effort therefore.
As an interesting side-branch of the potential anti-COVID-19 agents, completely different cyclodextrins have been shown to be active against several other, yet related viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. Of course, these discoveries are far from being approved and have no actual relevance in this year’s outbreak, yet CycloLab conducts ongoing studies and filed grant applications for finding the right cyclodextrin candidates that could be evaluated as potent antiviral agents, including actives against coronaviruses. This discovery hit the headlines in several countries recently:
- Swiss scientists discover ‘antiviral’ powers of sugar. Swissinfo
- Antiviral made from sugar ‘may be game changer for diseases like coronavirus’ BreakingNews
- ‘Game-changer’ antiviral sugar materials could be used against coronavirus. siliconrepublic
- Antiviral made from sugar ‘may be game changer for diseases like coronavirus’ yahoo!news
- A koronavírus ellen is bevethető lesz az új „csodafegyver” Origo
To wrap it up, from one way or the other, cyclodextrins will definitely play a crucial role in the fight against coronaviruses, this year and all the years to come.