Reply1Ecoool Turtle4 hours agoISCT Lung presentationYesterday we...

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  Ecoool Turtle4 hours ago

  ISCT Lung presentation
  Yesterday we were told that Meso “presented 90- day survival outcomes from the 222-patient randomized controlled trial of remestemcel-L in ventilator-dependent COVID-19 patients with moderate/severe acute respiratory distress syndrome (ARDS) at an invited presentation on July 17 to the International Society for Cell & Gene Therapy (ISCT) Scientific Signatures Series on Cell and Gene Therapies in Lung Diseases and Critical Illnesses. The results showed that two doses of remestemcel-L at days 3-5 conferred durable survival benefit through at least 90 days in the pre-specified subgroup of patients under age 65.”
  That first paragraph gives several positive indications even before we get into the great trial results.
  1. Meso is being invited to present at the top events in lung diseases – remember that Meso wasn’t even in the “lung space” a year ago and now they are the premier group in the world (certainly in the MSC sphere) with data from the large Covid-19 ARDS trial that others can only dream of. No one else has data like this.
  2. The ARDS trial data should provide all that the FDA requires in terms of MOA, manufacturing consistency and potency assays. This data wouldn’t have been available without the ARDS trial, particularly in large numbers, so it should help the negotiation for an EUA in ARDS, but also will be available for the OTAT meeting which I’m hoping could happen in the next month or so.
  3. We now have the 90-day ARDS data analysed and the results should be exactly what Novartis are looking for – it’s hard to see that NVS could expect much better results than this as an indication of efficacy for all-cause ARDS (except for the obvious PE miss).
  4. The dosage of “two doses…at days 3-5 conferred durable survival benefit through at least 90 days” – that means the dosage of one-quarter of the aGvHD treatment (2 doses per week for 4 weeks) is enough to protect under-65 year olds and therefore indicates the cost should be around one-quarter of the aGvHD cost ie around $US60,000 to $US75,000 assuming a cost of aGvHD of $US300,000.
  5. If we get a pre-EUA meeting with the FDA for Coivd-19 ARDS by the end of July, we would probably see NVS complete the agreement, or walk away, around the same time. NVS will then have an idea of the FDA’s thinking and will have seen all the analysis of the 90-day results. The August holiday season in the US will probably push this along. So, no guarantess, but it isn’t unreasonable to expect an answer from NVS within the next two weeks (could be in early August).
  6. The mortality reduction in under-65-year-olds at 90 day was 48% (p=.038), versus the 60 day figure of 46% (p=.048) - so the longer results were even better and more significant. The 60 day figure of 0.048 was significant, but it was close to the 0.05 cutoff, and I’m sure everyone, including Novartis, is happy to see that it went down to 0.038 on the 90 day results.
  7. The combination with Dexa in the under-65-year-olds remains a truly spectacular 77% reduction in mortality, with a stunning p-stat of 0.0037. Given that the original trial in all age groups was looking to reduce mortality by 43% compared with controls, and given that Dexa is now standard of care, it is likely that the FDA will view the mortality reduction in under-65s favourably, and could be the basis for an EUA.
  8. After an EUA is given for under-65s, a new trial with higher dosing for over-65’s could also be a way forward for that vulnerable age group (maybe second and/or third dose each a week apart would build on the good results seen in the first week for over-65s). This could be a subgroup within a larger Novartis funded All-Cause ARDS trial.
  Note that the reduction in mortality is via Kaplan Meier statistics which analyse reduction over the whole 90 day period, not just at the final timepoint. This is essentially an area under the curve analysis.
  Mesoblast then notes “Recently published guidance to industry by the U.S. Food and Drug Administration has recommended demonstration of mortality benefit for at least 60 days in critically ill patients. Mesoblast will be meeting shortly with the FDA to discuss the durable mortality reduction seen in patients under 65 years old who received remestemcel-L in this randomized controlled trial, and the regulatory pathway for remestemcel-L in this patient population.”
  1. This is as close as I believe Meso can come to saying that their mortality benefit meets the FDA’s guidelines – there is a clear mortality benefit in critically ill (under-65s) at 60 days and it is even better at 90 days.
  2. Meso will be meeting the FDA “shortly” – that could mean almost anything, but I’m hoping for a meeting by the end of July – it’s hard to imagine it would drag out past August given the urgency with the Delta variant.
  
  Bottom line – I feel that the latest two announcements show that we are now very close and that we could see some exciting developments by the end of this month.