This blog originally appeared on April 3, 2020 and has been updated on June 18, 2020 to reflect the latest insights gathered by our Life Sciences team.
As the race for a vaccine and treatment for COVID-19 continues, our team of Life Sciences experts have been leveraging our new COVID-19 Playbook to monitor vaccines in development, drug trends, and drug repurposing. The COVID-19 Playbook is a front-end user interface of the Signals Analytics platform, which connects data from a wide range of sources including clinical trials, research papers, media events, drug development and more, and extracts context using patented Natural Language Processing (NLP) techniques and taxonomies developed by domain experts.
To unlock free access to the COVID-19 Playbook, fill out our registration form.
This blog post contains their latest findings, and will be updated regularly. Please continue to check back for the latest updates or follow us on our social channels to be notified of new insights.
TMPRSS2, prostate cancer, and the link to COVID-19
In the early days of the COVID-19 outbreak, it became apparent that men have a higher infection rate and show more severe disease symptoms than women. At first, smoking, which is more prevalent among men, was thought to be a key contributing factor. Further studies, however, showed an inverse correlation between smoking and COVID-19 cases.
Scientists are now assuming that the answer lies in androgens (male hormones, such as testosterone) with a possible connection to a protein called TMPRSS2, which is commonly elevated in Prostate Cancer patients and is also responsible for the Sars-Cov-2 entry into the cell.
In this week’s update, we will review TMPRSS2 and the reported correlation between androgen levels and COVID-19, as well as recent reports on clinical studies of prostate cancer patients. Finally, we will examine what type of prostate cancer drugs may be suitable for COVID-19 treatment.
- The Signals Platform has identified an upward trajectory in research focusing on TMPRSS2 as it relates to COVID-19 (Figure 1)
- Evidence shows that COVID-19 as well as other coronaviruses depend on TMPRSS2 for viral entry and viral spread within the host cell
- TMPRSS2 expression is increased within prostate cancer tissue versus noncancerous tissue
- There is an ongoing debate as to whether androgen controls TMPRSS2 expression in the lung
Figure 1: COVID-19 publications related to TMPRSS2
Androgen Levels and Their Relation to COVID-19
- Studies are revealing that there is a correlation between androgen levels and susceptibility to COVID-19
- COVID-19 related male mortality has exceeded female mortality
- Men with male pattern baldness (an indicator for higher levels of male hormones) have been over-represented among hospitalized COVID-19 patients
Clinical Studies of Prostate Cancer Patients
- Prostate cancer patients with COVID-19 are being studied in part because of the relation between androgens and TMPRSS2 expression
- Studies have shown that prostate cancer patients taking androgen-deprivation therapies (ADTs) are less likely to be infected and be hospitalized than prostate cancer patients not on ADTs
Can Prostate Cancer Drugs Targeting TMPRSS2 be the answer?
- We have identified prostate cancer as one of the Top Ten medical conditions for drug repurposing efforts (Figure 2)
- Late stage clinical trials are testing TMPRS22 inhibitors (Example Drugs: camostat mesylate & nafamostat mesylate)
- Androgen inhibitors are being tested under the hypothesis that androgen levels can alter TMPRS22 expression (Example Drugs: degarelix & bicalutamide)
Figure 2: Medical Conditions associated with Drug repurposing for COVID-19
Observational studies linking COVID-19 with prostate cancer patients have led to promising repurposed drug candidates. As more epidemiological data becomes available, it will be crucial to continuously connect data types in order to surface promising treatments.
JUNE 1, 2020
Revisiting Our April 3rd Findings: Are Stem Cells a Valid Treatment for COVID-19?
On April 3, 2020, we reported stem cell therapy as a leading technology with the highest number of clinical trials. However, we noted in our findings the inconsistent data and low volume of supporting research around stem cell therapy at the time. In today’s update, we revisit stem cells as a potential treatment for COVID-19 and evaluate how the trend has evolved since our last analysis, across both clinical and basic research settings.
Stem Cell Therapy Clinical Trials
Between March 25th and May 15th, clinical trials assessing stem cell therapy for COVID-19 saw a global expansion, increasing clinical trial volume by ~320%.
- On March 25th, stem cell clinical trials were limited to APAC.
- By May 15th, trials have emerged globally, including 14 sites within the US alone.
Stem Cell Therapy Research Activity
During this same time period, research papers on stem cell therapy and COVID-19 experienced a similar expansion.
- On March 25th, only a single paper had been published.
- By May 15th, over 7 papers have been published within the last 3 weeks.
Conclusions & What to Expect in the Near Future
- Stem cells have been noted for their immunomodulatory properties, high proliferation rate, safety and efficacy, and long-term storage capabilities.
- Leading Stem Cell Therapy candidates include:
- GIOSTAR, which was granted FDA ‘compassionate use’ on May 6, 2020.
- Mesoblast, currently enrolling 300 patients for a randomized, controlled study to study efficacy and ARDS
- Despite the increase in clinical trials, controversies are ongoing regarding companies taking advantage of a more relaxed FDA compassionate use designation and direct to consumer preventative stem cell “therapies” being sold at a high price tag
- The corresponding research paper surge has begun only recently, and Signals Analytics will continue to track these trends in our COVID-19 App.
MAY 11, 2020
Corticosteroids as a Treatment for COVID-19
The Signals Platform has identified the Glucocorticoid Receptor NR3C1 as a leading biological target in COVID-19 clinical trials. However, there is much scientific debate as to its beneficial and adverse effects on COVID-19 patients. Let’s review the main findings so far and potential of ongoing trials.
Main Findings – A Concept Under Debate
Scientific chatter shows conflicting perspectives on the use of corticosteroids in treatment of COVID-19, asthma, and COPD.
Although systemic corticosteroids have shown some efficacy in minimizing severe symptoms in patients with SARS, inconclusive results due to trial design do not demonstrate a causative effect.
The absence of direct evidence has led to a debate concerning the benefit of the anti-inflammatory nature of steroids on patients in danger of cytokine storm, and detriment in clearance of viral load.
Much like the debate over RAAS inhibitors, existing guidelines are conflicting regarding whether a patient currently taking corticosteroids should continue or discontinue treatment.
Timing is Key
To establish consensus on the benefit or detriment of corticosteroids in COVID-19 treatment, the scientific community has ramped up trial and research efforts since January.
Signals Analytics COVID-19 Playbook has detected an uptick in research and clinical trials for both previously studied systemic corticosteroids (e.g., methylprednisolone, dexamethasone), as well as novel inhaled corticosteroids (e.g., budesonide, ciclesonide).
Many scientists believe that the efficacy of corticosteroid treatment is correlated with the timing of treatment within the patient journey. Similar claims were made with regard to the Plasma treatments as well.
So What’s Next?
In a recent drug screening of 3000 FDA and IND approved drugs, the corticosteroid ciclesonide was highlighted as being a notable antiviral candidate. Further investigation of corticosteroids, with the addition of more widely available diagnostic tools can allow physicians to assess corticosteroid treatment during optimal treatment windows.
APRIL 28, 2020
Top 5 Growing Molecular Targets Highlight COVID-19 Scientific Chatter and Treatment Focus
The top 5 molecular targets growing in publication volume over the past 3 weeks (March 30 to April 21, 2020) highlight key scientific discussions and needs in clinical trials.
IL6 and IL6R point to necessary treatment of COVID-19-induced ‘cytokine storms’
ACE, ACE2, and REN (Renin) showcase the interaction between the SARS-CoV-2 pathogenic mechanism and the renin-angiotensin-aldosterone system (RAAS), and the uncertainty around using RAAS inhibitors in COVID-19
IL6 / IL6R
Clinical trials are largely focused on IL6R drugs tocilizumab and sarilumab, with fewer trials for IL6 drugs olokizumab and siltuximab
This imbalance likely results from wider suppression of downstream IL6 signaling pathways via inhibition of IL6R vs IL6
IL6 has been linked with COVID-19 severity, and may be used as a diagnostic biomarker
REN / ACE / ACE2
RAAS inhibitors (including ACEIs) have been used to manage hypertension in COVID-19 patients, but concern over their effect on ACE2 expression, the receptor for the SARS-CoV-2 virus, highlights the urgent need to understand this interaction
REN COVID-19 publications discussing the safety of RAAS inhibitors in COVID-19 treatment have steadily increased since March 15
Trials using REN inhibitors have begun recently, as have several observational trials assessing the effect of RAAS inhibition on COVID-19 patients
APRIL 15, 2020
The COVID-19 Drug Repurposing Landscape
On April 10, Gilead published encouraging results for remdesivir, a repurposed Ebola drug. As of April 11, our COVID-19 Playbook tracks 414 clinical trials and 199 drugs and vaccines tied to COVID-19 related development.
Signals Analytics’ COVID-19 Drug Repurposing model provides a landscape analysis of drug repurposing across therapeutic areas, modalities, targets, and entities.
Oncology, Infectious Disease, Immunology/Inflammation, and Cardiovascular are the leading therapeutic areas with the most drug repurposing activity.
When data types are connected, repurposing candidates from surprising medical conditions, such as Pancreatic Cancer and Multiple Sclerosis, become readily apparent.
On March 19th, Merck KGaA donated its MS drug ‘Rebif’ to the French national research institute as a potential therapeutic for COVID-19.
COVID-19 Drug Repurposing in Oncology, Infectious Disease, Immunology/Inflammation, and Cardiovascular
We explored the leading therapeutic areas in deeper detail with our advanced analytics platform to surface the leading technologies, biological targets, and entities for each therapeutic area.
APRIL 8, 2020
Surge in Convalescent Plasma Research Ahead of FDA Announcement
Old, But Effective
Convalescent Plasma treatments have been with us for over a hundred years. In the context of a global pandemic, they were discussed long before the COVID-19 outbreak began, as can be viewed in this trending Ted Talk by Bill Gates from 2015, foreseeing the current outbreak.
As of mid-March, as more scientists have discussed Plasma treatment publicly, we have also seen a surge in the number Google searches for terms such “Plasma” and “Convalescent Plasma” in the US and across the globe.
Where We Are Today
On April 3, the US FDA announced a new national effort to facilitate access to convalescent plasma for treating COVID-19 via multiple pathways:
Access to convalescent plasma via an emergency investigational new drug application (eIND).
Approval for nationwide trials to evaluate the safety and efficacy of convalescent plasma.
As of April 8, there are 20 trials involving 31 organizations for the treatment of COVID-19 using convalescent plasma.
Using the Signals Analytics COVID-19 Playbook, these ecosystem movements can be well-anticipated from the research landscape.
Starting February 9, Signals Playbook began tracking a dramatic surge in COVID-19 Convalescent Plasma research.
Over the past 2 weeks, Convalescent Plasma has shown the largest growth (37%) in COVID-19 publications among technology.
COVID-19 Convalescent Plasma research maintains a high research paper strength and scientific rigor.
APRIL 3, 2020
A Deeper-Dive into the Top 2 Technologies Reveals Key Insights
Ranking modalities being studied for COVID-19 by clinical trial volume shows stem cell therapy as the leading technology with the highest number of clinical trials. However, taking a deeper look at clinical trials over time reveals that the number of mono-specific antibodies trials has grown steadily over the past months, whereas the growth of stem cell therapy trials has been inconsistent.
To further evaluate the clinical trials surrounding these top two technologies, we mapped out the clinical trial site locations and delved into trial details in the COVID-19 Playbook
Mono-Specific antibody clinical trials are being performed globally.
The entities running the clinical trials are more diverse, inclusive of big pharma, research organizations, and biotechs.
Many of these studies are for drugs that have shown efficacy for other coronaviruses.
Stem Cell Therapy
Stem cell therapy clinical trials are centralized in APAC.
The entities running the clinical trials are more focused within APAC.
There has been some skepticism, as some of the clinical trials designs do not prove strong efficacy.
For a more comprehensive assessment of these two technologies, we compared these modalities by research paper volume and strength. Mono-specific antibody is the leading modality across not only by volume and strength, but also in terms of research paper growth with consistent growth in research surrounding mono-specific antibodies being published. However, stem cell therapy, on the other hand, still shows very low levels of supporting research.
At first glance, stem cell therapy may seem to be the most promising technology based on the volume of clinical trials. However, diving deeper into the data for more granular analysis, as well as evaluating trends across multiple data types provides a more accurate and holistic evaluation of these technologies. With the COVID-19 Playbook, we were able to uncover the consistent growth mono-specific antibodies are showing across multiple data types.
To unlock free access to the COVID-19 Playbook and learn more about how advanced analytics can help in the race to a vaccine and other treatment drugs for COVID-19, fill out our registration form.