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Amryt Pharma’s Juxtapid (lomitapide) had a 7-point jump in its Likelihood of Approval (LoA) in familial chylomicronaemia syndrome (FCS) on the heels of positive data from an investigator-led Phase III trial.

https://www.clinicaltrialsarena.com/comment/loa-update-amryts-juxtapid-sees-7-point-surge-in-us-approval-prospects-in-familial-chylomicronaemia/

Amryt Pharma’s Juxtapid (lomitapide) had a 7-point jump in its Likelihood of Approval (LoA) in familial chylomicronaemia syndrome (FCS) on the heels of positive data from an investigator-led Phase III trial.

https://www.clinicaltrialsarena.com/comment/loa-update-amryts-juxtapid-sees-7-point-surge-in-us-approval-prospects-in-familial-chylomicronaemia/

AACR Annual Meeting is coming up and abstracts were published last night. Angle has a poster selected for presentation:-

'Investigation of PD-L1 expression in circulating tumor cells isolated using the Parsortix system in metastatic lung and breast cancer patients'

https://www.abstractsonline.com/pp8/#!/9325/presentation/1696

Good stuff - AACR is a big deal

Oh the irony and hypocrisy.

Wonder how Prof. Durrant is getting on in those cardboard labs?

Wild,

I have managed to find the research cited in the tweet mentioned by LL. The tweet was correct in that it did suggest that targeting the N protein produced a pro-inflammatory immune response with down regulation of anti-inflammatory cytokines. The researchers concluded that this caused an excessive immune response resulting in pneumonia. Sounds concerning but perhaps a little perspective is required. The research was actually from 2008, in mice and was against the original 2003 SARS virus. Just one 13 year old study in mice against a different virus, using a different vaccine type (recombinant vaccinia virus).

If there were any serious, known safety issues with targeting the N protein then I don't believe for one second any pharma/bio/academic would even consider developing a vaccine along these lines and if they did, for sure the issues would become apparent in preclinical/early clinical testing. So perhaps it's much better to look at up to date research into current vaccines targeting the N protein in Covid-19 rather than SARS and if at all possible looking at human rather than mice data. To that end you really have to look no further than the recent announcement of phase I safety data from ImmunityBio for their S & N targeting vax:-

'Safety assessments completed for first 12 participants and no serious adverse events (SAEs) reported; trials expected to be fully enrolled in Q2'

Small numbers perhaps but there are others out there also targeting the NP and I haven't been able to find any research to cause alarm. Of course you can't take anything for granted in clinical trials, especially safety and time will tell but if anyone is concerned then I'd suggest a little more research and reading might help.

LL

Any chance of a link to the tweet or the paper? - have looked and genuinely can't find it

AZN have now issued a statement:-

'We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis.'

In other words they're saying updated results are consistent with the interim results announced yesterday. Extraordinary behaviour from DSMB.

https://www.astrazeneca.com/media-centre/press-releases/2021/update-following-statement-by-niaid-on-azd1222-us-phase-iii-trial-data.html

Astonishing turn of events with NIH statement issued in the dead of the night. Important to try and make some sense of what's actually being said, although the lack of any detail from the NIH doesn't help.

The RNS from AZN yesterday made it clear that they were reporting data from an interim analysis from the US phase III trial, not the full results. During a media call yesterday Mene Pangalos did confirm that more cases had accrued since the interim analysis. So it seems the NIH's issue isn't that the data is wrong, more that it's that it's not up to date.

Just my opinion, but I suspect AZN rushed the data out to confirm that the DSMB had found no increased clotting risks and their attempt to reassure folks about the safety has rather backfired. I guess we'll only know when AZN respond and when the full facts are known whether this is just really poor communication and PR from AZN or what.

Either way, what a mess and what a shame. Someone on twitter yesterday described this vaccine as the workhorse of the world - there are so many countries that can't afford the cost of the very much for profit mRNA vaccines - confidence in this not for profit alternative is precious.

More good news from Amryt this morning.

The FDA have confirmed that they're willing to accept a single, 80 patient randomised trial for Myalept in patients with partial lipodystrophy over 12 months. Crucially, they've confirmed that they're willing to consider an efficacy supplement based on only 6-months efficacy and safety data - presumably this means that Amryt can file for approval after only 6 months if the data are good enough.

Good to note that there's a clear path forward and that involves a small study over a relatively short period. Approval should double the market for Myalept in the US.

https://www.londonstockexchange.com/news-article/AMYT/amryt-receives-positive-feedback-from-the-fda-on-the-path-forward-for-myalept-r-metreleptin-indication-in-partial-lipodystrophy/14909619

A cracking set of results from Ergomed:-

- Revenue up by 26.5% to £86.4m
- Gross profit up 34.6% to £39.7 m
- Cash and cash equivalents up 32.9% to £19.0 million at Dec 20
- Adjusted EBITDA up 55.2% to £19.4 million
- Order book up a stonking 55.5% at £193m

https://www.londonstockexchange.com/news-article/ERGO/audited-full-year-results/14909510

Not sure whether this has been discussed already but longs here will remember that Redx were forced to sell their BTK inhibitor when it was sent into administration by Liverpool Council. It's now owned by Lilly and has just reported very impressive clinical trial results. A quick search on twitter for Pirtobrutinib will give a feel for the very positive reaction from the scientific community. Bitter sweet for Redx as the terms of the sale didn't (couldn't) include royalties or milestones but it most definitely puts Redx on the map as a company that has developed at least one potential blockbuster and can only help to generate interest in the rest of the pipeline.

https://www.medpagetoday.com/hematologyoncology/leukemia/91533

Excellent confirmation this morning of the efficacy of the AZN vax. Assuming the FDA will now approve AZD1222, the interesting question now lies with what dosing regime will be approved? From today's RNS:-

'This AstraZeneca-led US Phase III trial included two doses administered at a four week interval. Previous trials have shown that an extended interval of up to 12 weeks demonstrated greater efficacy, which was also supported by immunogenicity data. This evidence suggests administration of the second dose with an interval longer than four weeks could further increase efficacy and accelerates the number of people who can receive their first dose.'

Another excellent RNS this morning with a reimbursement approval from France for Myalepta which follows on from the announcement of NICE approval back in January. Good to see Amryt quietly following their strategy of expanding the commercial reach of Mylatpta in Europe - agreements now in place with France, UK, Germany and Italy in addition to ROW territories inc. US.

Good stuff.
https://www.londonstockexchange.com/news-article/AMYT/amryt-receives-reimbursement-approval-from-the-french-ministry-of-social-affairs-and-health-for-myalepta-r-metreleptin/14907878

Excellent news today - from RNS

'In addition, Merck Sharp & Dohme Corp. has now subscribed for 654,023 ordinary shares at the issue price of $1.53 (£1.10) in the private placement, details of which were announced on 17 March 2021, thereby raising an additional $1 million (£0.72 million). '

Cleanerworld - must have missed that, do you have any details or links?

Burble ,

As clear a demonstration as you'll see of the need for randomised studies. The single arm phase II results for this drug produced 2 complete responses and a DCR of over 71%. From memory they were presented at ESMO to great acclaim and there were high hopes for the phase III. Seems likely now that the responses were just down to the ipilimumbab as evidenced by the randomised phase III results. A disappointing fail for all involved.

Can't draw too many conclusions for SCIB1 from this study - it was carried out with a completely different class of checkpoint inhibitor and in a different setting. The Idera study was in combination with Yervoy, a CTLA4 checkpoint and in patients who had previously failed on PD-1 treatment whereas SCIB1 will be in combination with a PD-1 inhibitor in patients being treated for the first time with any therapy for advanced melanoma. Worth noting that Yervoy has a much higher incidence of SAEs than Keytruda as reflected in the Idera trial.

rats is correct, it seems that the need for an effective combination therapy is as great as ever.

Not sure how scientific it is for a so called science journalist to announce an anecdotal case of cerebral venous thrombosis via twitter. Unless all evidence (hard evidence including results of autopsies) is viewed in context then it's all guesswork and that's exactly why pharmacovigilance has become an industry in itself. There are comprehensive processes in place to monitor safety which feed through to the regulators who can make an informed decision. The article below gives an interesting perspective.

Much better to wait IMO for results of EMA's investigation which hopefully will come later on today. If they confirm the AZN vax is safe and dosing resumes then who knows how much damage has been done in terms of lives lost due to missed vaccinations and loss of public confidence in both vaccines and the regulators? If they confirm there is an issue then that too will have the same result and also questions must surely follow about the safety of other vaccines. In the end, there will be no winners here - whatever the outcome, the damage has been done.

https://theconversation.com/blood-clot-fears-how-misapplication-of-the-precautionary-principle-may-undermine-public-trust-in-vaccines-157168

Ray,

Well spotted

WTP,

No, I probably shouldn't have used the word 'published' as I don't mean it in the sense usually associated with patents, substitute the word 'appeared' instead as I may have confused you.

It's a brand new patent application that has only recently been filed (2nd Feb) and the first stage in the processing is that it is listed in the UK Patents Journal which is basically a weekly update of patents filed, published and granted.

It will now undergo a preliminary examination and search and all being well will be published around 18 months from the filing date, at this stage we'll be able to access all records online including the claims, the full description and all correspondence. Once published the patent will undergo substantive examination which can be a very lengthy process. So there's a way to go yet. It's not until the patent is published and we can read it online that we'll know for sure what it covers.

Another new patent application from Scancell has been published in the UK Patent Journal today:-

GB2101435.2 Applicant: Scancell Limited
Title: Nucleic acids and polypeptides encoded thereby
Date Lodged: 2 February 2021

https://www.ipo.gov.uk/p-pj?startYear=2021&startMonth=March&startDay=10th+-+6877&endYear=2021&endMonth=March&endDay=17th+-+6878&filter=scancell&perPage=10&sort=Publication+Date