Covid-19: Hydroxychloroquine, Remdisiver, IVIG, Vaccines

From an MD helping treat COVID-19 Patients (Initial post on 4/2/20) with a background in molecular biology to help preface what people should be reasonably expecting from these treatments in logical/mechanistic terms:

(-) Hydroxychloroquine: (Sanofi/SNY) It doesn’t work as a treatment in my opinion. It is a classic petri-dish versus human problem. It stops/reduces cell virus entry, which is great if you use it as a prophylactic as it will increase the required viral load needed to become infected. As a treatment though, when you have 50,00,000 copies of virus already, reducing the spread isn’t the same as treatment. I believe unfortunately by the time the virus is showing symptoms, a person has too many copies of virus so slowing the rate of repeat cell entry does not make a clinical difference. 9If you were going to die from the virus, you still will and HCQ won’t make a difference) Further paper have demonstrated no real clinical difference from HCQ/azithromycin combinations and medically we have moved past using this as it just exposes patients to risks of side effects. The theory behind it is founded on a laboratory model that cannot be necessarily safely replicated (due to dosages) in humans. Would you rather die from COVID-19 or from HCQ overdose stopping your heart?

Overall: cheap medication with limited clinical benefit. Most upside has already been unraveled, greater risk than reward at this point in my opinion investing in companies behind this.

[ HCQ: Don’t expect much going forward. ]

(+) Antivirals (Gilead): Possible area of research, but generalized research into antivirals as a broad class leave a lot to be desired. Used in combination with other medicines target other mechanisms of action they seem to work (HIV treatments) but in isolation they limit reproduction of virus. At >50,000,000 copies the damage might be done though. The thought is the same to “flattening the curve” / slowing down virus replication to give your body time to fight it off. I think this will be an adjunct to treatment long term but given production constraints of remdisivir I don’t think the swing will be that large. (/”priced in” at this point from an actual bottom line to companies standpoint) This is like a hydroxychloroquine idea that actually likely works but even then has likely limited benefits just thinking mechanistically. Long term, I think the studies will show that people that get remdisivir early do a little better when controlled trials are released. (On the order of, 20/50 critical patients die without remdisivir versus 15/50 critically ill COVID-19 patients die with remdisivir. Useful as a drug, but not a game changer for COVID-19 at all)

Overall: expensive medication with possible clinical benefit. Long term will add to Gileads portfolio but seems somewhat ‘priced in’ at this point. Speculative play against COVID19 only.

[ Remdisivir: Could have limited benefit, but absolutely not a silver bullet for COVID-19 even in the most rosy of speculations. ]

(+) Tocilizumab (Chugai, La Roche/RHHBY): An IL-6 blocker, one of the important co-factors in the cytokine storm which is likely the factor that kills people. IL-6 is something cells release to tell the body to ‘release the bombs’ which can unfortunately end up killing a patient before the virus can be cleared by said bomb. Limiting its potential upside is the fact that it’s immunosuppressive and we don’t have a lot of long term data on how COVID-19 interacts with immunosuppressed people. I have become less bullish on this from my previous post given production constraints and cost of the medication (to produce and deliver)

Overall: expensive medication with likely clinical/mortality benefit but severely limited by production constraints. Limited background market outside COVID19.

(+) Sarlimumab (Sanofi/SNY, Regeneron/REGN): Similar to tocilizumab, also an IL-6 blocker.

Overall: expensive medication with likely clinical benefit but almost too expensive and hard to produce to really make a big impact. (like tocilizumab)

[IL-6 blockers: Could be beneficial, but limited by production constraints and costs, baseline limited market outside COVID-19]

(++++) IVIG (Grifols/GRFS, CSL Behring AG/CSLLY, Baxter/BAX): This is other people’s plasma. Like vaccinating someone else, pulling out the antibodies they made against the virus, and injecting them into someone else. At baseline has a good market (CAGR ~7.6% estimated over the next 4-5 years prior to covid) for multiple sclerosis and other autoimmune disorders that ‘flair’. The theory being that injecting other peoples premade antibodies to the virus will kill the virus in a targeted way while also mitigating the immune reaction and keeping your body from killing itself. Personally I’m extremely bullish on this and Grifols in particular as that is the product most hospitals seem to use around my area. CSL Behring also has a reported subcutaneous formulation which could keep people out of the hospital for infusions, limiting exposure/spread of virus as well.

Mechanistically this is the closest thing to a vaccine we can have short of the vaccine itself. It is less promising than a vaccine because its time/labor intensive to collect (you have to suck out other peoples blood) and doesn’t stop the spread of the disease, unfortunately, but can be useful to stop people dying from it.

Overall: Involved process of colelction with baseline shortage (mitigated by the fact that people donate more plasma during economic downturns, the financial crisis of 2008 was associated with an oversupply of plasma). Likely to have a large clinical benefit (From a clinical and mechanistic standpoints) and may become a mainstay of ICU treatment prior to more directed therapies/vaccines. Has a baseline market (other disorders) that will only increase in the background long term. Safety of a stable market/demand with upside as a massive treatment for COVID-19, and easing of a previous shortage due to increased plasma donation as well as a future market growth.

[ In my opinion the safest long term bet with also the highest upside of clinical benefit to patients short of a vaccine. You get the benefits of a good baseline market that requires repeat doses over their lifetime (multiple sclerosis, other autoimmune diseases), plus you have the upside of increased revenue streams from COVID-19 associated treatment, and you turn from a shortage constrained market to healthy supply of market as people rush to give up their plasma for an extra $500/month in their pocket, in which the company turns around and sells said plasma to the hospital for $10,000]

(++++) Vaccine: A vaccine is the ultimate treatment, unfortunately there’s no way to pick which company will be most successful. I expect the first vaccines to not be very effective. All this to say, picking a vaccine company is impossible at this point with the available literature base currently. You could try to assemble all of the companies working on a vaccine that have a separately good pipeline to try to play the eventual massive swing when a vaccine is announced and limit downside when it’s not the company you picked.

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