Antivirals Rather Than Vaccines For COVID-19
Jul. 7, 2020 8:26 AM ET
The likelihood appears slim of an adequately effective and widely available vaccine being in commercial use before H2 2021.
Demonstration of the production of antibodies against SARS-Cov-2 is certainly no guarantee that adequate protection against COVID-19 will be forthcoming.
Non-vaccine antiviral agents hold greater promise than vaccines for the management of COVID-19.
Press releases from BioCryst Pharmaceuticals and CytoDyn about the anti-COVID efficacy of galidesivir and leronlimab, respectively, may be imminent.
If results for galidesivir and leronlimab are positive, then July increases in share price for BioCryst and CytoDyn may be to well above the $10 mark.
Will an anti-COVID-19 vaccine be effective?
Much has been written about the potential of multiple vaccines to ultimately prevent COVID-19, the condition caused by the SARS-CoV-2 coronavirus. However, despite Operation Warp Speed and the immense hyperbole surrounding vaccine candidates in the COVID-19 arena, the likelihood appears slim of an adequately effective and widely available vaccine being in commercial use before H2 2021. Indeed, COVID-19 might prove resistant to vaccination. It should also be remembered that the FDA has approved no effective vaccine against other coronaviruses (e.g., those causing the common cold, Middle East Respiratory Syndrome, or Severe Acute Respiratory Syndrome).
Given the scale of the COVID-19 pandemic, the threshold of efficacy for a vaccine against SARS-CoV-2 is understandably quite low. For FDA approval, a vaccine would have to be at least 50% effective in preventing or reducing the severity of COVID-19. Dr. Anthony Fauci believes that it’s a question of “when, not if” a vaccine will be introduced, but that any first-up vaccine might only be 70–75% effective. He acknowledges that this is inadequate protection and that many people will refuse to get a coronavirus vaccination even if it becomes available.
Unanswered questions also remain: e.g., What duration of immunity will any vaccine provide? Will coronavirus mutations - e.g., the D614G mutation on the spike protein - actually make the virus more infectious and any vaccine candidate less effective?
Of course, all this is against the backdrop of recent encouraging results from BioNTech (NASDAQ:BNTX) and Pfizer (PFE) regarding their early-stage COVID-19 vaccine BNT162b1. Yet, doubt again starts to emerge in vaccine strategies when there are rumors that Moderna’s (MRNA) critical phase 3 study of its COVID-19 vaccine, mRNA-1273, has been delayed. So, have the BNTX results been over-hyped? Some may think so, and it should not be forgotten that demonstration of the production of antibodies against SARS-CoV-2 is certainly no guarantee that adequate protection against COVID-19 will be forthcoming.
Given the significant level of “doubt” about vaccine candidates, it’s appropriate to look at how particular non-vaccine antiviral agents, which reduce coronavirus replication or are viricidal (kill the virus), are progressing through R&D in the COVID space. I’ve tried to focus on compounds with significant antiviral activity that could be effective earlier in the disease course (i.e., immediately after a positive test result for SARS-CoV-2). I’ve also avoided compounds being investigated solely to treat acute respiratory distress syndrome and the cytokine storm of COVID-19.
Gilead and remdesivir
Gilead (GILD) is up and running with its Emergency Use Authorization (EUA) for remdesivir. A price of $390 or $520 per vial has been set, and the Department of Health and Human Services has secured 90% of GILD’s remdesivir production (one half million treatments) through September. Optimistic revenue projections of approximately $2 billion in 2020; and $8.5 billion in 2021 have been listed. However, significant doubts remain regarding whether GILD will overcome its remdesivir supply problems, and even about whether remdesivir is particularly effective: anecdotal reports from frontline healthcare professionals suggest that remdesivir may only be minimally effective in patients with COVID-19.
BioCryst and galidesivir
BioCryst Pharmaceutical’s (BCRX) galidesivir is another RNA replicase inhibitor, but it may have better and more diverse antiviral activity than remdesivir. In recent weeks, BCRX has been ominously silent about galidesivir. The reason for this is the ongoing phase 1 study (NCT03891420), which is being conducted by Dr. Esper Kallas at the University of Sao Paulo, Brazil. The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID). The NIAID Director, Dr. Anthony Fauci, wants to avoid any premature “trickle” of results into the public domain, as occurred back in April this year for remdesivir.
Importantly, the BCRX trial started in early April, and a key outcome is mortality at 8 weeks. Given the extent of COVID spread in Brazil, there will be no shortage of patients for the trial, which can soon be expected to have meaningful data. Speculation suggests that a Fauci-authorized press release from BCRX about the anti-COVID efficacy of galidesivir may be imminent. Before July end, an EUA for galidesivir from the FDA may manifest.
As mentioned in an earlier article, GILD released (Apr 10) data for the first 53 patients treated with remdesivir in a compassionate-use program. By May 1, the GILD share price had increased 14%. Given the contemplative clinical advantages of galidesivir over remdesivir, together with the increasingly urgent need to introduce effective treatments for SARS-CoV-2 infection, positive news for galidesivir might increase BCRX share price to greater than $10 before July end. Of course, there’s also the possibility of BCRX being acquired [perhaps by Abbvie (ABBV) or Johnson & Johnson (JNJ)], not just because of galidesivir but also because of other particularly promising pipeline products (e.g., berotralstat).
CytoDyn and leronlimab
Leronlimab is generating much interest and excitement and is currently under review in the US for HIV infections. This monoclonal antibody and CCR5 antagonist inhibits coronavirus entry into healthy T cells, protecting the cells from infection, thereby limiting viral propagation, and reducing viral load. According to the Biologics License Application Acknowledgment Letter that CytoDyn (OTCQB:CYDY) received from the FDA, a PDUFA date may be announced on July 10.
CYDY recently released efficacy data from a compassionate-use program in 10 critically ill patients with COVID-19: leronlimab restored immune function and significantly reduced plasma viral load. Further, in a July 3 press release, CYDY emphasized that a phase 2 study in the US (NCT04343651) has met its 75-patient enrollment target in mild-to-moderate COVID-19. Enrollment continues in a CYDY-sponsored phase 2b/3 randomized clinical trial (NCT04347239) in patients with severe COVID-19.
In a DrBeen webcast on July 4, Dr. Nassar Pourhassan, the CYDY President and CEO, spoke at length about leronlimab potential. CYDY initially expected data from its phase 2 study to be available approximately two weeks after enrolment of the last patient. Therefore, the release of results is likely imminent, and many people are expecting definitive reductions in critical endpoints such as time to clinical resolution and 14-day mortality rate. Another decisive factor for CYDY is the supply and distribution agreement recently signed with American Regent, Inc. CYDY will supply leronlimab for the treatment of COVID-19 for distribution by American Regent and will receive quarterly payments based on a profit-sharing arrangement.