Notes from Needham Presentation - 4-5-2011
The portion of presentation discussed below was made by Will Lewis, President (Lewis' background is interesting because he is a hedge fund investment guy, not a medical/scientific guy which I didn't realize until I went to the AEGR website to see what his background is):
Lewis asserted that when they originally went to the FDA with a placebo controlled study design, the FDA told them that would be unethical (it wasn't stated during the presentation why) and that the FDA actually provided a grant for the funding of this study). Study was originally designed to be a 78 week study at the conclusion of which AEGR would file its NDA but after the FDA saw the safety and efficacy data last July, the FDA said AEGR should move forward and file their NDA after the 56 data comes in. The efficacy data shows that 1/3 of the patients are achieving LDL levels under 100; unprecedented reductions especially when one considers that these patients are already on maximal lipid lowering regimens. Also asserted that the gastrointestinal side effects are mild to moderate; that the diarrhea is not "uncontrolled" but rather this is a "loose stool based on a high fat meal." "The key to unlocking the absence of GI side effects is simply diet control." When the FDA saw relatively benign hepatic fat data (see slide 17), the FDA wanted AEGR to take this compound to broader patient populations but AEGR resisted saying that they are focused on the most severe patients. AEGR says they have had a lot of dialogue with the FDA and this is why they "have such strong conviction about our progress forward and why we are excited about this year as our filing year and next year as our launch year."
Interestingly liver steatosis after lomitapide turned out to be transient and fully reversible. Three studies on the very ineffective ISIS product? All in heterozygotes, far easier to find and to treat
My very last point, Bio, ISIS studies were not escalating dosing. They did escalation dosing in the lab but not in their clinical studies. But all of your other points are valid. Why would the FDA hog-tie ISIS with placebo controlled trials, non-escalating dosing, requiring that the same injection site by used(which by the way would be considered malpractice if a physician told their diabetic patients to keep giving themselves injections of insulin in the same place), and yet this good ole boy action from the FDA in regards to the MTTP inhibitor? It doesn't add up Bio. I have to leave, I've made the same points over and over and am becoming redundant myself. Only time I've seen this kind of actions from a CEO was with PARD and they went from $8 to 41 cents. Enjoy you're company and input and you'll know where to find me. t
My one last note and then I'm gone for good from this site. Listen to the competitors CC at the 1:37 mark in the Q and A session and then draw your own conclusions. Four lipidologists noted that the intestinal steatosis was a HUGE ISSUE that would NEED to be addressed before approval of one of these agents. t
I think chesaresus' point that the slightly less that 30 HoFH patients in AEGR's Lomitapide study is a reasonable number given the small number of such patients world wide is probably valid. In this regard, ISIS' phase 3 HoFH trial data enrolled only 34 patients.
But the inquiry should not end there. ISIS has 3 other phase 3 trials that the FDA will be able to consider. And, if I am not mistaken, all of the ISIS phase 3 trials are placebo controlled, dose escalating, studies.
In light of the statements made by AEGR's Will Lewis at the Needham conference regarding his assertion that it was at the FDA's objection to AEGR's initial proposal to conduct placebo controlled studies that AEGR dispensed with same, how are outside observers supposed to evaluate this claim? Are we to believe that the FDA made such a comment to AEGR but not to ISIS? Aren't placebo controlled studies the sine qua non of rigorous (and therefore valid) scientific investigations of new drugs?
With regard to chesaresus' statement that there is much previous, non-phase 3 experience with Lomitapide, I don't see how this will carry much if any weight with the FDA. Is there any support in recent FDA decisions relating to other compounds that would permit an investor to reasonably conclude that the FDA can be expected to look favorably upon Lomitapide given these facts? (I think the weight of the evidence is contrary but I am always willing to be persuaded if the evidence is presented.)
[And Jet, please don't leave this board. Your input is extremely valuable.]
The thing that brought me to this board in the first place was the outlandish claim by the CEO that their competitor that had already completed FOUR phase III trials and hit all of their primary, secondary, and tertiary endpoints will make a great second line agent behind AEGR's compound that hasn't even completed their 29 patient phase III trial yet. If you chose to believe that and everything he says, God bless you. I'm leaving this board but will watch from a far. I'd recommend that everyone here listen to the competitors last CC before they put a big bet on this company with the people who exhibit duplicity IMO. t
Again, I think you sir are acting like a mini-FDA. The old data, that's going to count? With this FDA? With the fact that the big pharmas abandoned the med? The fact that there could be organ-organ interactions that aren't known even by lipidologists and people who are in the lab with this post Vioxx-FDA? No one knows, myself for sure either, but I wouldn't bet the farm on what I've seen from this FDA, maybe you will and will be successful, but I hope you have good friends to help you through if things don't pan out. I do know alittle about HoF, and what you've said is surprising in that context. t
." When the FDA saw relatively benign hepatic fat data (see slide 17), the FDA wanted AEGR to take this compound to broader patient populations but AEGR resisted saying that they are focused on the most severe patients. AEGR says they have had a lot of dialogue with the FDA and this is why they "have such strong conviction about our progress forward and why we are excited about this year as our filing year and next year as our launch year."
Two points Bio, one is that the FDA had requested more data and AEGR refused. Mistake one, just because they have had a dialogue with the mysterious FDA they think they can push on anemic study through....mistake two. It's impressive how the CEO backs up his conviction with his own money. I hope he has good friends that can help pick him up off the ground if he's wrong. t
I am really enjoying our continuing dialogue about AEGR.
With regard to point 1, I think the presenter's point was that the safety data was so benign, the FDA thought that larger populations would likely benefit from expanding the study beyond the most severe populations. Your take overlays a very negative frame or cast upon what was stated by the AEGR presenter. If one accepts your view, is it even remotely possible that AEGR's management naively believes their public statements regarding the substance and tone of their FDA conversations? In other words, if your take is correct, could any outside observer believe that AEGR's management unwittingly but sincerely misinterpreted the FDA's comments?
Since I think the answer is "no" to my stated question, I still have trouble believing that AEGR would be able to entice their new CEO, Beers, to join in a charade designed to mislead the investing public. Beers has clearly stated he read the July, 2011 meeting transcript between AEGR and FDA and has endorsed a very positive spin on behalf of AEGR's lomitapide.
Frankly, I am flummoxed because I am persuaded by your view that the clinical trial data seems entirely inadequate to gain FDA approval. Too many other drugs have failed to meet stringent FDA hurdles for me to think that Lomitapide won't meet the same fate.
However, I also must admit that I have no scientific or medical backgound upon which to draw and therefore will remain confused about what is really going on here.