Member Info for Peelweight

Matterhorn, I am not sure but two possibilities are

1) they started with significant structural or functional lung damage prior to being enrolled thus cannot get full recovery and would skew the results, or

2) being a novel therapeutic, it was decided not to include these patients with the most precarious of pre-COVID respiratory conditions in trials.

sorry 2->3

ACTIV2 inclusion RNS 25th Jan
ACTIV2 first patient dosed 15th Feb
Dr Castro thinks 110 dosed "in the next few weeks"
If we assume by 10th June, that would mean 4 months to get 110 done. And he says circa 1000 for P3 ACTIV, though that number will be decided later from a power calculation after the ACTIV2 readout. The rate of recruitment is not fast but would be much quicker for ACTIV3, if it happens, as sites will be fully set up and used to using it. Indeed the USGov may add lots of sites to those drugs that progress from 2 ->3 as they have cleared the first hurdle and will be seen as more worthy of focussing on? All IMHO

Thanks Alphageddon, really interesting. I was drafting an email to Synairgen to point out that there are a few of the inclusion criteria for the other ACTIV2 trial drugs that make sure the patients enrolled are higher risk. I had been hoping it might have been possible to only recruit significantly breathless patients for SNG001 in ACTIV2. I can see it is too late to change pre-P3 ACTIV. The good news is that if any signal is visible at all, and the FDA/USGov have access to our HT too, they may commit to a full P3 home ACTIV in only those that are markedly or severely breathless on the OSCI scale at presentation.

Anyway we will have 110 more patients that will add to our safety data, and may add to a meta-analysis no the subgroup that the HT science has indicated we should focus on - marked or severe breathlessness.

I am somewhat concerned that ACTIV2 seems to have disappeared from the Synairgen site apart from the news of inclusion and first dose. Hopefully that is not a bad sign. Great to hear Dr Castro thinks it will be weeks until last dosed SNG patient in ACTIV2!!

Absolutely!!

As RM said, it is very fortunate that the inclusion criteria for SPRINTER includes not just being admitted to hospital but also the need for supplemental oxygen (a treatment for breathlessness/low oxygen saturation). Thankfully that means that we are including only the exact group that Synairgen thinks SNG001 should be best for.

It is my view that at the end of this day of mass change in share ownership, IIs with strategic plan for the hospital P3 will have scooped up a fair percentage of the company. 10M+ changed hands already today

TR1s next week?

Shpunken, for me the statements today say we are now very focussed on hospital P3. Less so ACTIV2 now. Remember HT was high risk group and only had 3% admission rate (2 from about 60). ACTIV2 are not so purely high risk so may have less hospitalised rate. Saying that, we now have a sub-group analysis that we will swiftly be looking at (Breathless patients at home).

The results of this study are not surprising. It was always going to be very diluted ill-health prior to hospital. Studies are always useful and this one has further narrowed our search for the right group to treat but not as far as Scinv says (autoantibodies only). Our ongoing analysis going forward will be looking at patients with marked or severe breathlessness.

Q2 is April to June

Thin, I suspect none of us know for sure and AJ did only say he "highly doubts it". If I was to chip in, I would say your list will be helpful for SAFETY side of any EUA application. And the small number of asthma/COPD patients that have been trialed will also chip in for safety. For example the safety data for all humans treated with SNG001 for any indication in any setting to date were mentioned in the application for ACTIV2 inclusion.

Thereafter, an application will be for a certain type of use, and will use the efficacy data for that use as justification. So the HT will be added to ACTIV2 in a meta-analysis of an EUA application for home use. And the P2 Hospital will be added to the hospital P3 in a meta-data application for hospital use. All IMHO

Thanks Borsaci, that's really helpful

https://www.google.co.uk/amp/s/www.nrru.org/amp/sprinter-study-a-phase-3-trial-of-sng001-in-patients-hospitalised-with-covid-19

Good to see Nottingham about to join in P3. Expanding at home as well as the addition of new countries

Gov publication says "A competition to identify a chair for the Antivirals Taskforce will be launched shortly, and further details on the structure of the taskforce will be set out in due course."

https://www.gov.uk/government/news/government-launches-covid-19-antivirals-taskforce-to-roll-out-innovative-home-treatments-this-autumn

It is also very clear multiple times it wants to find a couple of "pills or capsules" to help in the fight after home diagnosis.

Maybe Prof Sir Holgate would offer himself as a possible chair?!

Should have said, I have not seen the SPRINTER protocol so can’t say with any certainty

Mike, it depends on exactly what the trial protocol says will happen with the data and the DMC. It won’t be to do with one country “finishing” their allocation, allocations can be changed by minor amendments of protocol/ethics. It is more likely the DMC will have a pre-determined peek at the data to look for futility or a strong enough result to decide efficacy and safety and stop the study at a planned number of recruits. All IMO

Well done picking this up WD. Sadly it is a June start there. "04/06/2021". I initially hoped it was the American system and read as 6th April but it is not as the first global case recruited is listed as "12/01/2021". Actually 13th Jan from memory. And I think this will not now change as it seems to be on this official Indian gov site. Each ethics committee will have been asked to consider the same paperwork and it will include these dates.

I suspect what happened here is that we listed many possible countries so as not to miss having location(s) with enough cases. It did not look fruitful to focus on India initially - low cases per head of population. So Parexel didn't focus there first. Given the changes in incidence they have pushed more for a start date for India and it has turned out to be very slow getting going. Remember this trial still represents a quick roll out of a multinational RCT believe it or not. Comparatively breakneck speed for a novel "investigational medical product". Though I do admit it now looks to be drifting from RMs initial plan for timings.

Yes SGD27, if they Synairgen hold ethics for it and have kept bloods from the participants (likely nowadays) they will indeed be able to look retrospectively at their blood bio-bank to answer such questions as they crop up.

Thanks Tornadotony for this and all your chart education over the months! Much appreciated.

I believe IFN1 auto-antibodies will be present prior to COVID and during. No timing issue here IMO.

Agreed WD. Especially that the UK has, for a long time, been an benchmark used around Europe for price-setting. However other companies use a tool called a “Managed Access Scheme” (MAS) or similar to shield that commercially sensitive information from other countries.

“Pricing the product at a level consistent with securing a positive NICE appraisal may be achieved through the NHS list price proposed, or through a confidential discount or other commercial arrangement agreed with NHS England or other relevant NHS body.”

So a headline price is set. He NHS company then asks he NHS to actually pay less privately. The NHS only cares about what it actually pays and it passes the test NICE sets in value for money (value-based pricing) and the company gets to keep its price confidential internationally.

I know this sounds crazy but it is otherwise almost the only country where there is a single price paid and it is public. Also the medicine is bought in bulk for the whole population if it works for that indication and has no competitor that can offer that care

The MAS may not be needed, I am just trying to fill out the discussion. If the NICE judgement is that £2000 per treatment course is value, no skullduggery is needed. This seems plausible for the hospital P2 indication, if backed up by similar data in P3. However value-based pricing calculations seem much tougher if a weaker signal from HT and Activ2?

All IMO

Thanks WD. This represents the change from the previous PPRS (pharmaceutical price regulation scheme) to the current system that is a form of value based pricing. Basically, as I understand it, some of the elements of PPRS continue to be in place, rewarding all the spent money getting the new drug to market etc. However the value--based pricing element says that if NICE would not give you a positive finding at that price you can't charge it. It makes the way forward more complex in the UK but does not have any impact in the US or elsewhere.

Still worth pursuing the UK and Synairgen will certainly be doing so as we are a country that treats everyone, not just the affluent. Once registered, the system looks manageable. And remember COVID has chucked out the previous "rule-books" in many many regards. Vaccine approval in 11 months not average 10 years. That needed expedited ethics/funding/trials/approvals. A whole new world, so a lot of latitude would be granted for a useful therapeutic in many jurisdictions IMO, including the UK