Van BioBoyScout van het Yahoo forum nav deJefferies call van vandaag :
I just got of the Jefferies-Alpha1 call. Special thanks to Maury Raycroft for providing me with an invitation. I believe Maury to be a straight shooter and I have nothing but respect for him and his talents. The call lasted just over an hour - here's a quick rundown of what was covered.
Maury spoke with Dr. Kyle Hogarth of the Alpha One Antitrypsin Deficiency Clinical Resource Center at the University of Chicago. Dr. Hogarth's A1 Center is a Center of Excellence for A1 patients. Much of the call was focused around Arrowhead's ARO-AAT drug, with some additional discussion about Vertex's drugs.
Comments from Dr. Hogarth:
Alpha1 is underdiagnosed because it's rarely tested - if physicians look for it then they find it pretty frequently. Alpha1 is not a lung disease per se, it is more of a liver disease. There are probably much more than 100,000 ZZ patients in North America because that study showing that number is from 15 years ago. Alpha1 distribution was thought to be Northern European, but they're now learning that is also of Spanish and Persian descent, which extends the population much more worldwide. Genetic testing for Alpha1 is part of the algorith for 23andMe, this helps identify and let people know that they're Alpha1.
Dr. H pointed out that carrier patients (those that have only one Z gene) are also at risk for liver disease. He didn't say the percentages, but it sounds like Arrowhead's drug would also be able to treat these patients as well.
Dr. H considers this to be not that rare of a disorder. There was a natural history study in Sweden that showed 1 in 1,100 births were ZZ - 20% of which have a risk of developing some level of fibrosis or cirrhosis in their lifetime. Some patients present the disease early and others later - it is unknown why. Tackling liver disease is the most important and most exciting for Alpha1 patients because that's the worst part of the disease. The second leading cause of liver transplant in children is A1AT.
Dr. H's thoughts on Arrowhead's drug - the data is unbelievably compelling. You can't shut the gene off, but you can close down its message. Taking it a step further, ARO-AAT doesn't just reduce A1, it also reduces gene expression related to fibrosis in the mouse model (and this alters the natural history).
Dr. H was asked if Arrowhead's 91% reduction in phase 1 for healthy patients was meaningful. Answer - YES, because of the large reduction. Dr. H believes that biopsies after taking ARO-AAT will show improvement, as there is no reason not to see improvements in the liver. Dr. H went so far as to say that he would be "unbelievably surprised" if they don't see improvement in the liver, and that Arrowhead will probably see what they're expecting to see.
The discussion then shifted to Vertex. Dr. H didn't sound as excited about Vertex's drugs as he did with Arrowhead's. Do Vertex's drugs allow normal function? Maybe. It's a different mechanism than Arrowhead, but he needs to see the data first, as the data that was released by Vertex did not include everything he wanted to see. He would like for Vertex to release "all" of the data. The theory is that you can raise circulating Alpha1 levels - this could then help the lungs and also possibly the liver.
So while Dr. H's Center is in discussions with Vertex for one of its studies, he appeared to be more excited about Arrowhead's drug, but hopeful that Vertex will be able to also deliver.
Those are the highlights that I believe were most important. My two key takeaways: 1) there appear to be a lot more Alpha1 patients out there than originally thought, not just in North America, but worldwide; and 2) the Alpha1 community is excited about Arrowhead's ARO-AAT drug, as the data to date is very compelling that it will greatly help.