Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
An interesting study looking at how a combination of PCR and rapid antibody tests can be used to increase diagnostic accuracy for COVID-19. The authors note how this utility could be particularly useful in resource poor settings. Yet another potential use for rapid antibody tests. One thing is for sure, the demand for testing is going to continue to increase for the foreseeable future.
https://www.cam.ac.uk/research/news/combining-pcr-and-antibody-tests-at-point-of-care-dramatically-increases-covid-19-detection-in
Chiron - you raise some good points on the role of the different tests. This is why I think there will be a place for many different types of tests (when they all become available), as they will have different utilities depending on their relative strengths and costs.
As well as false positives, the old problem of false negatives is true of PCRs, especially if self sampling. Therefore, the utility of a self administered saliva based LFT will always deliver more consistent results, albeit with perhaps slightly less sensitivity in an ideal world. The latter point is not one that should be lost, for all of the wonderful S&S results delivered in the labs, the real world S&S is what is required to tell the true story and typically real world results don't meet the idealised lab reported results. CONDOR is thought to be of help here, but we have yet to see any published data from CONDOR yet, I still remain hopeful CONDOR will deliver.
So the saliva based test will likely deliver more consistent true results (vs PCR), be self administered and quick. It's utility will likely be different to that of the PCRs/other delivery mechanisms and so we should all remain positive.
I would like to understand more about their proposed mechanism of clinical validation - if it's not CONDOR, it's not the end of the world as some may think.
PS - completely agree with your sentiment on restoring the discussion on the BBs to be more grown up, some of the recent childish posts have just been an unnecessary distraction.
Agreee pl75, we need more rapid testing and I see it a good sign that Roche are in.
Timster - far be it from me to call a company that makes $10bn a year on diagnostics useless. I think their test will have utility. The avacta one, if meeting specs has the potential to be even broader.
Roche dropping news of their antigen test. 15 mins result time, 96.5% sens and 99.7% spec. Still an NP swab and requires a healthcare professional. CE marked and 40mil tests ready at the end of the month. It’s not a saliva test that anyone can use but because it’s Roche, governments and large customer groups will be targeted. Be good to hear news drop soon about the avacta test.
https://www.roche.com/media/releases/med-cor-2020-09-01b.htm
CO, would be very pleased if these were the figures for the Avacta test. Has any data been released on the epitope binding properties? This will help to hone in on spec. Is the affimer binding to the RBD or the entire spike protein? Another feather in the cap, if this is in line with their launch plans, would be to tie in any mass screening efforts with a registry aka the test and trace app. Many possibilities, many potential uses.
Nostra- in my opinion, and I'm probably low balling it, specificity in the 90s and sensitivity at a minimum of 85%, probably higher. If the labs show that RT-PCR is of the order of 99-100% using lab conditions, LFTs will never match this, the assay is not as sensitive. Add in real world conditions of CONDOR and saliva not carrying as much virus as deep NP swabs, I think the figures will be of this magnitude. Would I be disappointed if these were the figures -definitely not! For one thing, the PCR tests are reportedly not done correctly up to 30% of the time. Hard to get a spit test wong. Test results are also available instantaneously, not so readily available with PCR, although rapid PCR tech is coming on stream, it still will not be as quick and simple as a saliva LFT. The key thing will be educating people that this is a good, accurate, fast test that can let people get on with their day.
I’m with folk in that there’s room for plenty of different types of assays and we need them all, thanks for the updates on some of the other assays in development. Agree Matt 2521, there will be other variables with the saliva sample, but I would not expect it to effect end result as much as those that affect the PCRs, just my opinion there and not based on any research.
Be good to hear more of those like dr gottileb talk to the other tests which have other advantages rather than gold plated accuracy. Having just one measure of effectiveness in mind of those purchasing decision makers is what I think needs addressing, but maybe it’s already getting there.
The results will tell all doze, but what makes you think it will be 99% accurate if saliva doesn't allow for counts less than 20000 copies/mL?
Agreed PL75, more good reasons. I think both tests will co-exist (along with others as we desperately need them), but I think it will take some effort to those in power to get their head around the sensitivity levels for the saliva test, especially if they don't understand the other benefits.
Governments will need help to get around headlines such as less accurate tests etc. All achievable, but it requires some effort to get there.
I've come across some interesting articles recently that got me thinking about the market receptivity for the saliva test. A recent publication comparing swab to saliva found only 5% concordance where viral load was <20000 copies/mL. From this, it's could be said that saliva contains fewer copies than a NP swab inserted deeply into the NP cavity. Other publications have shown that sputum actually contains higher loads vs. swab.
https://www.famhp.be/en/news/coronavirus_evaluation_of_the_use_of_saliva_samples_as_an_alternative_to_sampling_via_a_deep
One may think that the LFT is automatically less sensitive than a PCR, less reliable to use in different real life scenarios and inferior overall. However, although highly sensitive, PCR assays are difficult to reproduce consistent accurate results repeatedly and still take a certain amount of time to gain results. In fact, it has been reported that 20-30% of results are false because sampling errors are usually reported.
In effect, one is positioning PCR as a highly accurate test that can sometimes give you an accurate results due to common operator error in sampling vs. a less sensitive test (LFT), let's say 85% sensitive for arguments sake, but it will always be 85% accurate, because it only requires a saliva sample which is easy to give.
Whatever the established sensitivity is, a lot of education will need to go into explaining to large (government, employer) purchasers as well as smaller (consumer) that getting a result that is less sensitive almost 100% of the time is better than using a test that is 99% accurate only 70% of the time, especially when that result is available in 15 mins. Only by doing that, will use be encouraged and people have the confidence to get more of the economy going. Do others think the same?
Nolupus - do you think SNG001 is competing with AZs inhaled therapies? SNG 001 is being trialed as a short term therapy for cold and flu virally induced exacerbations whereas AZs inhaled LABAs/LAMAs and ICS various combinations are for maintenance therapy. The two would be complementary (as per the SNG001 protocol in COPD). Unless I am missing something here? Do AZ also have a therapy for short term use that is targeted to fight cold/flu induced exacerbations?
Agreed Jimbooo, managing expectations will also be important from here on in.
CONDOR is gold standard in terms of validation for anything that could be used for mass screening and this potentially answers one question about route to market.
What level of sensitivity would be required for this utility? Interesting that the Roche diagnostics CEO recently commented on their own antigen test development at 80-85% sensitivity not being good enough for mass screening. For a massive company like Roche, mass screening would be core to their business plans, but for Avacta, I can see other utilities being equally important if sensitivity is at this level. All will be known soon and good news on the RNS today, things are falling into place nicely.
There is a huge need for further effective COVID therapies, that being said, regulators won't and shouldn't compromise on standards required for efficacy, safety and quality for use in a broad population.
There are avenues for pre-licence access in most countries, for example in the US - EUA, in the UK - EAMS, and compassionate use/named patient programmes. Such avenues are used for patients who are facing life threatening/serious situations and no treatment options or where public health emergencies exist. For example, these avenues are commonly used in patients with some types of cancer (EAMS or compassionate use programmes). Although the world has moved on since the early part of the year and now there are treatment options for some patients e.g. ventilated patients can have dexamethasone (off label), and oxygenated patients can have remdesivir (licensed in EU), a huge unmet need still remains for many serious COVID patients.
For more information on these schemes the following links may help.
https://www.gov.uk/guidance/apply-for-the-early-access-to-medicines-scheme-eams
https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization
I think there will be pressure for access to SNG001 through these schemes, however, these schemes do not enable collection of high quality efficacy and safety data, as would be collected in a study.
Regulators will likely have many questions about SNG001 in COVID patients. For example, how can the results seen in 50 patients exposed in a Phase II study translate to an indication that would benefit a broader range of COVID patients, were the differences in efficacy observed in the ITT population consistent in the sub-populations, it looked like from one analysis that patients in the oxygen treatment group may respond better, what is known about the role of IFN inducing chemokines/cytokines that may be responsible for the cytokine response seen in severe COVID patients...? to name a few.
So far, the results from the Phase II look very impressive, and I'm a believer and want to see the drug do well.
The regulators should ask the awkward questions associated with protecting public health, they'll also be well aware that there have been many instances in the past of Phase II results not being replicated in Phase III, but they will want to see replication to some degree, for confirmation of effect.
It is for those reasons that I think a Phase III study will be required, and I think all support that the government can give, will be provided, whilst at the same time some form or pre-licence access programme will also exist for those patients most in need. This is just my opinion!
I think david brent captures it best when referring to bojo, to assume is to make an ass out of u and me.
Interesting indemnity offered by govts to AZ for the mass vaccination in the absence of long term safety data for their vaccine.
https://www.investing.com/news/coronavirus/astrazeneca-to-be-exempt-from-coronavirus-vaccine-liability-claims-in-most-countries-2247104
This doesn't mean that regulators and companies will employ shortcuts on going for the highest quality product, or compromising assessments on efficacy and safety, but it does give AZ a get out of jail card.
Great find Nolupus, speed is definitely the driver here along with the limitations that remdesivir brings in terms of effect size as well as use in a restriced population. I do wonder if there is a jingoistic vibe across the pond with the use of Avonex (Biogen) to supplement remdesivir (Gilead), both US companies.
In any case, with this being an adaptive trial, it enables the potential inclusion of another arm i.e. inhaled interferon later.
I have posted on a potential combination with remdesivir before and there are certain aspects of this Phase 3 I find surprising. Remdesivir has been shown to be efficacious in moderate patients requiring oxygen but not at the severe end in those requiring ventilation. I wonder how long ethics committees/IRBs and DSMBs will allow a monotherapy remdesivir arm in the ventilated population to continue?
It would be great to see SNG-001 included in this study, there is a point to investigate if there are any additive/synergistic effects and having a drug that can be administered direct to the lungs is more beneficial than an injectable. Clearly, if SNG-001 is included in this study later, it can only be for those not on ventilation.
I still think the bigger opportunity is in the patient population the company are exploring first i.e. mild/moderate at home and in hospital as monotherapy. Epi studies all show about 80% of symptomatic cases are mild. The patient population is already broader than that for remdesivir.
Lastly, a trial in asymptomatics would top everything off, and this would be a game changer, showing that eradication of infection in community before spreading, would enable people to shorten self-isolation, go back to work/school and not be infective.
All is all , great possibilities ahead!
Publication of the Phase II results (which includes peer review) can take some time, and typically longer for the top tier medical journals i.e. NEJM, Lancet. Given that the data are still 'raw' and the IR announcement is made as soon as available, the data is then verified internally i.e. checks are made on missing or contradicting data, the clinical study report and the manuscript for a journal are written (this is more that happens). Typically, these things take quite some time to get right, even for a Phase II, we are talking months. However, from what we have seen with the neck breaking speed of other COVID related developments, things have been going faster, and with a 100 patient study, these steps will be easier to complete.
The peer review is part of the publication process and Synairgen will write the manuscript, so it is the company's take on the dataset, that is reviewed and commented on by the journal and peer reviewers. Again, for top tier journals, this can take up to a year, as some of the other posters have commented. I think this publication will be fast tracked. It will be useful for all audiences as the amount of data published is clearly a lot more than available on a single A4 RNS or even a PDF presentation NS and the questions about primary endpoint, sub-populations etc, can be put to bed conclusively. I wouldn't expect it overnight, but I suspect the company are doing all they can to get the publication out there rapidly.
A couple of interesting recent developments.
https://investors.sorrentotherapeutics.com/news-releases/news-release-details/sorrento-announces-license-columbia-university-rapid-site
A rapid and highly sensitive (97%) LAMP test giving results in 30 mins now seeking FDA EUA, but I don't see how this test, that still requires heat (67oC) can fulfil the range of utility the company claims i.e. true, at home testing. Maybe airport or fixed place of work where you can still have access to the required heat source?
Nanoscent developing a test based on smell.
https://www.youtube.com/watch?v=BRKgI4vRm94
Quite ingenious, but with 85% accuracy, and the need for additional equipment, again, I think they'll struggle to find uptake on the scale they'd like, unless they price it such that it becomes viable. Again, I can't see the range of great utility for this one, although I think it's a big step up on taking random temp checks! I heard of dogs being trained to detect the scent of coronavirus too.
All interesting developments, and all still point to the every present need for a rapid POC with high sensitivity that can actually be used in a wide variety of POC settings like the Avacta saliva test. Looking forward to news, when it becomes available.
Thanks Peter, I'm not an expert on all this share price movement, but it doesn't worry me. The fundamentals speak for themselves and there is now a solid base to work from. These guys are experts and I think they will now attract other experts on their journey to help them on their way.
Interactions with health authorities are probably going at full pace, and I suspect they are discussing early access (EAMS - MHRA, EUA - FDA, and named patient access or compassionate use programmes) as well as what will be required for a broad label in mild patients i.e. locking down the Phase III design. Compared to normal development, these things will be going at a frightening pace and I suspect health authorities will expedite processes wherever possible, given the effect size already demonstrated in the Phase II as well as potential public health benefits the product could bring.
For me, I expect more good news, once the company have had their HA interactions and can share news and/or announce production deals and/or funding options (which, in my view, they would have no problem fulfilling).
Morning all, I’m a newbie to this board and invested as soon as I saw the press release.
I can see great value from Synairgen, not only in the short term with the opportunity for SNG001 in mild patients as monotherapy to prevent deterioration and promote recovery from COVID-19, but also in the longer term with additional indications.
If the ‘at home’ study can demonstrate the ability to prevent hospitalisation and further deterioration in patients with mild symptoms, then the entire mild symptomatic patient segment could be owned by SNG 001. All epi studies to date have demonstrated that the majority of patients suffer mild disease. Thus, the market potential is already larger than that for remdesivir.
Additional indications could include a potential study in combination with remdesivir for patients with mild/moderate disease to test for any additive/synergistic effects, if positive, then repeat the study with the inhaled version of remdesivir is available to reach an even broader group of patients.
Another potential expansive indication could be for asymptomatic infected patients, most epi studies point to a sizable asymptomatic population, who themselves are not using healthcare resources but can infect others, who may be more vulnerable. Even if we take a point estimate of 40% of incident cases being asymptomatic, again the potential for expansion is huge. A study that first demonstrates clearance of the virus in infected patients oro and nasopharyngeal tracts (this could be built into existing and future studies) and I would think has a high likelihood of success, could be followed by a study of asymptomatic patients to demonstrate removal of infection in asymptomatic patients, thereby preventing firstly progression and secondly, further infection of contacts. Such a study would require a rapid point of care diagnostic, and these will be available soon.
Prof Holgate as a founder and involved in the products development is a huge bonus, there isn’t much he doesn’t know about respiratory medicine. And all of this before any talk about COPD.
A drug with a potential for asymptomatic patients through to mild/moderate makes a market cap of 300m seem light.
Back to the short term, what will the discussion with the regulators bring? I suspect that there isn’t sufficient data for a full licence at this stage, given that based on the available data (which would include bridging to the safety profile of injectable interferons), not all of the regulators questions could be answered for a good label.
Rather, I suspect discussions with the FDA to focus on EUA, MHRA on EAMS and potentially named patient and compassionate use programmes for rest of world to happen in parallel with discussions on the Phase III required for a full licence. This may allow use in the near term whilst additional studies are being conducted.
Exiting times ahead indeed, just my views. GLA.
Looks like this one will go live soon in Italy at 11 bob a pop and gives results in 12 mins and reported to be highly sensitive. https://www.thetimes.co.uk/article/italy-tests-coronavirus-swab-that-gives-accurate-result-in-minutes-6wfxm38kp
The good news is that utility in an airport setting is being justified at a price point that I don't think people will scoff at. Over 1000 samples tested vs reference and reportedly good results.
It would be good to get an update on the avacta test soon, the avacta test will have greater utility for sure, but there is a point to get to market and get contracts soon.