Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
Hi All,
Waterloo on the guild has pointed out a critical study where the results are due any day now. Over 1k of patients in the study.
Severe SARS-CoV-2 infections are frequently associated with the acute respiratory distress syndrome (ARDS), which leads to a mortality of 30-40%. An altered type I interferon (IFN) response has been demonstrated in patients with severe COVID-19, together with a high viral load. A recent study revealed that 10% of patients admitted in the intensive care unit (ICU) for severe COVID-19 had positive type I anti-IFN antibodies. Such finding has potentially important therapeutic implications, as patients having positive anti-IFN antibodies could benefit from targeted interventions, including plasmapheresis. The aim of the current work is, in a large cohort of patients with severe COVID-19 admitted in the ICU, to determine the prevalence of patients with positive anti-IFN antibodies and to determine their outcome, as compared to patients having negative anti-IFN antibodies.
https://clinicaltrials.gov/ct2/show/NCT04733105
The team know what they are doing. Within regulatory package you need to show the most benefit to charge the highest price. We are most likely to show the most benefit to hospital patients therefore this is our focus. After approval for hospitalised patients if further evidence subsubstantiates use for the outpatient setting then this could expand patient use. However the price for SNG001 would be much higher. If we had approval for outpatient first the price would be MUCH lower.
Molnupiravir use is for early in the disease only. In the P2 study it was shown that it didn't work so well for hospitalised patients. This was one of the reasons for the change to high-risk patients with less than 5 days in the infection in their P3 study.
Patients need to get drug within 5 days of testing positive. Many people go for days with the virus until they start experiencing symptoms so certainly questions the effectiveness. So far it doesn't look like they are targeting specific patients this is where RM has pushed since the home trial results. We know that patients most likely to benefit are those suffering from breathlessness, we also have various studies outlining those with interferon deficiencys are prone to larger risks. This plays in SNG001 favour as we can specifically target patients and show larger benefits.
Will Molnupiravir be the saviour for mankind? No but it will be a useful tool. For those questioning SNG001 the demand will still be sky high.
www.sciencemediacentre.org/expert-reaction-to-interim-analysis-of-oral-antiviral-molnupiravir/
I believe someone in the guild directly asked RM about the change in nebulisers. His response was that they had received approval and had increase the dose given. The result was that 20% more of SNG001 made it to the lungs.
Hardly groundbreaking results with a dealth rate being at 24% compared to 30% in the placebo group. Also this was only for the seronegative patients cohort of patients. When they looked at the whole of the population REGEN-COV had NO effect.
This drug is also the active comparitor within the Activ2 trial. The do not test for patients for serostatus.
https://investor.regeneron.com/news-releases/news-release-details/regen-covtm-casirivimab-and-imdevimab-phase-3-recovery-trial
Hardly groundbreaking results with a dealth rate being at 24% compared to 30% in the placebo group. Also this was only for the seronegative patients cohort of patients. When they looked at the whole of the population REGEN-COV had no effect.
"No such benefits were seen in the overall trial population (combining patients with negative, positive, or unknown serostatus)"
https://investor.regeneron.com/news-releases/news-release-details/regen-covtm-casirivimab-and-imdevimab-phase-3-recovery-trial
Our P3 is global and is being run Parexel Biotech. No one will be looking at the data (including FDA) until synairgen release it. For this to happen the trial needs to complete and the data is locked. The results we be analysed internally before regulators across the world can access.
Very good video and easy to understand. However I should point out that the MRC won't know anything material I think they have only posted this as the know results will follow in the next few months. Nevertheless I will be up 7am Monday.
Our findings demonstrate that this coronavirus has devoted a significant proportion of its genome to block IFN-I production, presumably in order to help it establish early stage infection. Nevertheless, this virus remains sensitive to the effects of added interferon, providing an opportunity to treat COVID19 patients with IFN-Is therapeutically.
Interestingly, while the antiviral potency of IFN-Is on SARS-CoV is only moderate, SARS-CoV-2 seems to be highly sensitive to exogenously administered IFN-I, indicated by a significant reduction in viral replication following IFN-I treatment [21,22]. Moreover, IFN-I inhalation therapy (but not necessarily systemic injection) was shown to provide promising clinical response to COVID-19 patients
It is not at all clear however if IFN therapy has clinical application for patients with well-established infection, where the host IFNas are endogenously being produced. A possible exception to this counter argument however, is that for a large subset (~10%) of patients with life-threatening COVID-19, neutralizing antibodies to IFN-Is (particularly IFNa and IFN?) have been detected in patient serum, this which is almost never found in the general population, and which almost certainly is blocking the potent anti-viral effects of IFN-Is, hence contributing to the severe pathology of these patients [78]. For this subset of patients with life-threatening COVID-19, we suggest that therapeutic intervention with IFNß may have life-saving effects, particularly because added IFNß provides a robust anti-viral response to SARS-CoV-2 cells (Fig 1) and due to its divergent sequence to other IFN-Is, should escape IFNa/IFN? antibody-mediated neutralization.
In summary, our findings support a multi-gene process in which SARS-CoV-2 blocks IFN-production, with ORF7b as a major player, presumably facilitating evasion of host detection during early infection. However, SARS-CoV-2 fails to suppress IFN-I signaling thus providing an opportunity to exploit IFN-Is as potential therapeutic antiviral drugs.
htTps://pubmed.ncbi.nlm.nih.gov/34437657/
Presentation on Activ2 early this month probably worth including in this thread.
https://rethinkingclinicaltrials.org/news/august-13-2021-got-anything-for-this-cough-outpatient-treatment-trials-in-the-time-of-covid-davey-smith-md/
Gives more info regarding the activ2 trial and graduation to P3. Was good to hear that the p2 isn't just about safety and has to hit endpoints. His comment about Camostat failing and that "Synairgen and Sab are still going on" is confirmation things are going well. P3 is geared by the FDA and is all about reduction in hospitalisations/dealths with EUA attached.
The Q&A at the end from 47 mins was interesting.
The interviewer asked about plans for the next 2-3 months the below was the response.
"Yeah in the next two to three months we will have a version 7 open and in the field with our active comparator, so there's a little bit of back-and-forth with the FDA right now but we should be very close and then getting that active comparator, those sample sizes are much larger, there's 600 for the infused agents and 800 for non-infused....."
"And then after version 7 we have an activ-2b that is starting up with new clinical research organization and a new group trying to get other agents, that'll be basically what we did with activ2 just in a different setting"
I think this is just a case of under promise and over deliver as it's likely the V7 will be up and running shortly.
It's worth asking the good doctor a few questions about SNG001. From the video before he was really existed about inhaled or a pill treatments. Well Camostat (pill) is no longer part of the trial.
"We are looking at a bunch of medicines that look really exciting. There are some that are injected, some that are inhaled, some that are pills. And can you imagine if we have an inhaled or a pill medication you could take to prevent you from spreading the virus to other people?"
https://www.kxan.com/news/coronavirus/thousands-needed-for-covid-19-treatment-research-how-to-sign-up/
P3 progression shouldn't be to long a wait now.
https://newsroom.uw.edu/news/people-covid-19-sought-study-test-therapies
The below comment IMO is RM calling for a tweak in the protocol for Activ-2 to move to p3 and inclusion in the UK's covid Therapeutics taskforce.
"What we want to do is find the breathless people at home, which is probably only about 10% of the non-hospitalized population"
Ahh thanks. As expected SNG001 wasn't going to mentioned as one of these 5 promising treatments since they are not part of the rolling review undertaken atm. We are much more likely to be selected as the other treatments that they hope to start rolling reviews before year end.