Advances in mitigating long-COVID symptoms using Erdosteine
The long-term effects of COVID-19
The severity and acuteness of COVID-19’s symptoms, combined with its rapid spread, led to an extraordinary, collaborative effort from scientists all over the globe, to provide a response and help save lives. As a result, multiple COVID-19 vaccines were formulated after less than a year in development, and since then, more than 11.2 billion doses of various COVID-19 vaccines have been administered. These have saved lives by helping to reduce the severity of symptoms and the spread of infection.
However, even now as more and more countries loosen restrictions, the virus is still having a negative impact for many people - particularly those who experienced severe pneumonia as a result of COVID-19 infection. For these people, the virus has had lasting effects on their respiratory system due to lung inflammation and scarring, resulting in long-term symptoms such as dyspnoea, fatigue and a persistent cough. This is collectively referred to as “long COVID”. Therapeutics that can minimise the long-term effects of COVID-19 will be critical for restoring the quality of life of people suffering from this debilitating condition.
A potential solution: Erdosteine
With research into the long-term effects of COVID in its infancy, medical professionals are still trying to identify the most effective treatments for people with ongoing COVID-19 symptoms. A molecule that has recently emerged with the potential to significantly improve pulmonary function in long-COVID patients is Erdosteine. Erdosteine was first discovered by Edmond Pharma, a Recipharm Group company, within their research and development (R&D) facility situated in Italy. It is a thiol derivative drug classified as a mucolytic agent, which has a multitude of properties, such as the ability to produce antioxidant, anti-inflammatory and antibiotic enhancing effects.
Erdosteine’s therapeutic effect in patients suffering from chronic and acute respiratory disorders is well documented and it is prescribed in more than 40 countries worldwide. Due to its efficacy in restoring respiratory function in patients suffering from diseases such as pneumonia, Erdosteine’s use as an effective treatment for long-COVID was tested in multiple countries throughout the pandemic.
Testing Erdosteine as a treatment for long-COVID
The first study to evaluate the performance of Erdosteine as a treatment for recovery from COVID-19 associated pneumonia, was a study carried out by Santus et al. 2020. This observational study used various types of patient questionnaires concerned with measures of health-related quality of life (HRQol) as well as measures of dyspnoea impact, in order to assess Erdosteine’s efficacy as a treatment for COVID-associated pneumonia during the first 15 days after discharge from hospital. This included measuring the impact of Erdosteine on overall health, daily life and perceived well-being (SGRQ) as well as its impact on the effects of dyspnoea at rest (VAS), during daily activities (mMRC) and during moderate exercise (BORG).
Two weeks after hospital discharge, patients reported a statistically and clinically significant improvement to their overall HRQol, as indicated by the increase in SGRQ total score. In addition to this, the impact of dyspnoea at rest and dyspnoea during daily activities also improved significantly, shown by improvements to VAS and mMRC respectively. This study provided hope that Erdosteine could be an effective treatment for persistent COVID-19 symptoms.
Further to this study, Feshchenko et al. 2022 undertook a similar study whereby SGRQ and mMRC were measured at the time of discharge from hospital and then measured again 30 days following discharge after 300mg of Erdosteine was orally ingested twice daily. Similarly to the previous study, SGRQ and mMRC scores improved significantly after 30 days compared to the control group, and clinically important changes were observed in HRQol and symptoms.
Both of these studies detail the potential to use Erdosteine as an effective treatment against long-COVID symptoms, particularly dyspnoea, and its usefulness in assisting patients in making a full pulmonary recovery after suffering from COVID-associated pneumonia.
Manufacturing Erdosteine for long-COVID treatment
Following positive results regarding Erdosteine’s eligibility as a long-COVID treatment, Edmond Pharma, along with Recipharm’s support, undertook process development work to establish a viable commercial manufacturing process for Erdosteine. Recipharm has now filed and published a patent, with the subject ‘Preparation of Erdosteine or a derivative thereof using a continuous flow process.’ The application presents the novel manufacturing methods used to produce Erdosteine, Recipharm’s original drug product.
Specifically, these innovative manufacturing methods make use of flow chemistry - whereby a chemical reaction is run in a continuously flowing stream, which has many advantages over traditional batch manufacturing. It is an approach that enhances process safety for both operators as well as the facility, while also having the capacity to produce a drug substance of such quality that it is even sufficient to be used in injectable forms. In addition to this, the relative ease of setting up the production system renders the method fairly efficient regarding manufacturing times. Importantly, the flow manufacturing method devised for the production of Erdosteine uses non-toxic reagents/solvents, supporting our group-wide sustainability vision.
Looking to the future
With the current available studies supporting the prospective use of Erdosteine to mitigate the effects of Long-COVID and potentially support a full pulmonary recovery in patients with COVID-19 associated pneumonia, this molecule demonstrably has promise.
Recipharm is well-positioned to support pharma companies in their endeavour to help patients suffering from long-COVID in the future with our efficient and sustainable flow chemistry methods for the manufacturing of Erdosteine.