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>>XELJANZ 5mg monotherapy did not meet its primary endpoint of non-inferiority versus Humira plus MTX or versus XELJANZ plus MTX [oops]
It was worth a shot, and doesn't really hurt the drug that they failed to show monotherapy worked. In some sense this was a trial of MTX more than anything else. So this trial had upside (it would be a big deal to be able to drop MTX) but no real downside - they are really no worse off now than before.
The INCY trial just reported in NEJM had good results. So the saga of the small molecules vs. biologics is not over yet.
>>Is there any rational reason to think a pan-PPAR would be unlikely to encounter safety issues in the clinic?
Starts with a couple of strikes against it, but they could always get lucky I suppose. It's been a big problem for this class of drugs that animal models haven't been particularly good predictors on safety.
>>AKBA
Looks to me like these are not anemia-related compounds.
It's only $1m because AKBA couldn't afford more - so I assume JNJ made up in royalties and milestones for the paltry upfront.
Basically neutral I think - the increased burn is the negative. It's possible AKBA understands something JNJ doesn't so could always be a hidden gem in there someplace.
>>I'll take the over on that.
And I'll take the "under."
Sort of product where there will be a struggle to get reimbursement and educate doctors. The benefits happen five or more years down the road from procedure - that's beyond the event horizon for most insurers.
Yes, you are correct - it is a time-release drug. I was mislead by the "administered with MMX" language.
Be interesting to see what sort of uptake they get. If it makes colonoscopies quicker and easier for the doctors I think that would produce better uptake than "merely" finding more lesions.
Peter
>>what they are offering is a drug, not a device.
They seem to talk about some device to distribute the (cheap generic) methylene blue stain within the colon.
Here's a video:
TRIL abstract title:
Intratumoral delivery of TTI-621 (SIRPaFc), a CD47-blocking immunotherapeutic, inhibits tumor growth and prolongs animal survival in a subcutaneous B cell lymphoma model
>>biotech investors have become desensitized to these kinds of pronouncements.
The fact that the messaging from Trump is quite inconsistent from day-to-day adds to this.
But I do believe there will ultimately be some kind of deal that allows some degree of negotiation by Medicare.
>KTOV
"Kitov's flagship combination drug, KIT-302, intended to treat osteoarthritis pain and hypertension simultaneously,"
I stopped reading right there. :)
>> risk of diabetes
That one I believe. It's not a huge risk, but there definitely is a signal for higher dose statins after a few years.
I'd say there was at least as much evidence that statins are associated with improved cognitive functions as there is to the contrary.
Some of the evidence reviewed here:
https://www.dovepress.com/serum--low-density-lipoprotein-levels-statin-use-and-cognition-in-pati-peer-reviewed-fulltext-article-NDT#ref10
Any observational study is going to be flawed though - people on statins will tend to be better educated.
Books like Grain Brain (not a book I've read personally) tend to take something with a kernel of truth and then magnify and exaggerate it. Thus they don't usually present evidence that conflicts with their world view.
That is not to say there might not be individuals that do suffer cognitively when they take statins. The statin/myopathy connection is instructive - a blinded trial of those that claimed statins caused muscle pains showed only about half of the claims to be valid. (And interestingly, COQ10 supplements did not help these subjects).
No, it's actually real - happened in a number of early trials:
Cholesterol and violent behavior.
https://www.ncbi.nlm.nih.gov/pubmed/8002683
Observational studies don't really back this up (some say yes, some no), but you would almost certainly expect people with low cholesterol to be be more likely to be non-smokers and less engaged in risky behavior. So I think there probably is a (weak) signal here - the brain certainly needs cholesterol. So not just a case of people driven to violence/suicide by a boring diet.
Peter
Agreed, but the extremely low-cholesterol diets that were faddish some decades back did drop LDL some. But they seemed to also increase deaths from accidents and suicides.
I'd add that low-cholesterol diets have been similarly ineffective at reducing mortality and bile sequestrants are another class of cholesterol-lowering drugs that don't actually do anything good.
I'd add that niacin clearly reduces LDL levels - from 74 to 65 in the big NEJM study that showed excess mortality.
So basically I believe that lower cholesterol is indeed good, but you have to be careful how you achieve it because homeostatic feedback loops kick in that tend to reverse any benefit.
I also believe that excess homocysteine over long periods is a problem - less of an issue now in the US that folic acid supplementation has been introduced and many people take vitamin supplements that include B6 and B12 anyhow.
Peter
I'll reply to everyone in a single post.
My take on Zetia is borrowed largely from an ex-editor at UpToDate that was responsible for surveying the literature in this area. The IMPROVE-IT study was people who had recently had an ACS despite lowish cholesterol, so not necessarily relevant to a broader population. Also Zetia has some anti-inflammatory effects outside cholesterol.
On cholesterol itself, fibrates and niacin both significantly lowered cholesterol and had zero impact on cardiac markers and generally a negative impact on overall health.
Here's PCSK9/statin (and fibrate) interaction:
https://www.ncbi.nlm.nih.gov/pubmed/18547436
More later if I get a chance.
Peter
>>[PCSk9] further validates the importance of lowering LDL cholesterol for those with lipid disorders such as hetero FH and also for CAD secondary prevention
Not in my view. The issue is that lowering cholesterol upregulates PCSK9. So adding say Zetia to a statin will indeed lower cholesterol further, but the effects will be largely offset by increased PCSK9 - the massive IMPROVE-IT trial showed no benefit in overall mortality in a very high-risk population.
In general, apart from statins, drugs that lower cholesterol pretty much do nothing to cardiac risk, likely because of this effect.
>>Do you mean just in terms of U.S. investor friendliness?
Yes - very hard for a US investor to get a handle on what they are doing.
Ono seems very opaque - think most of the Japanese pharma are.
Peter
Ono just got a nice portion (25%) of the MRK patent settlement with BMY - significant fraction of their market cap.
I actually still hold Ono - likely will dump it now seeing they seem to be heading for an overpayment for some US company.
>> Lasmiditan's 2020 sales.
I'll go with around $100m. Lot of variables I don't know of course, mainly how hard LLY will push on sales and marketing.
Well we'll see how this pans out in practice. I still predict sales will disappoint - insurers will be reluctant to cover.
Neurologists currently aren't afraid to prescribe triptans to all patients, but I guess LLY may be able to scare some PCPs into using the new drug.
I think ICER is going to be the standard here. At some point insurers are going to start taking their recommendations seriously.
ICER thinks PD1 drugs are very over-priced. But basically they were OK with the HCV drugs.
It was two patents denied review - 8,609,646 and 8,466,172
The hepcidin patent likely serves to block AKBA in US as well given any FDA label would talk about use for epo-resistant patients with high hepcidin.
Surviving this review bodes very well for chances of these patents surviving given lower standards of proof and broader claim construction here.
I can't really complain about Medicare being able to negotiate for drug prices on all the drugs it buys. Not good for my biotech portfolio, but ultimately good for the country.
Not in least similar. And AKBA win was in Europe and not done deal yet.
FGEN/AKBA more like the recent AMGN/REGN case.
Peter
>>MNTA
I've lost track - what's the status of their patent suit? Might be a significant hidden asset that not many are thinking about.
Peter
From Jim when the stock was in the 2's:
https://www.thestreet.com/story/12081443/1/ariad-pharma-the-contrarian-long-thesis.html
The recent study showing THC helped with obstructive sleep apnea is of interest.
I'm generally skeptical that there will be much actual drug research done here - no patents and so no money for proper trials. And also very hard to do blinded studies of any kind.
Peter
Note Fibrogen has some potentially blocking patents in the US - no idea whether they will hold up - I have always assumed not.
Here's one:
The present invention relates to methods for treating anemia in a subject having a low percent transferrin saturation by administering to the subject an effective amount of a compound that inhibits hypoxia-inducible factor prolyl hydroxylase activity.
>>The counter-argument is that the real harm from smoking comes not from the nicotine, but from the tar.
I agree on that, which is why a low-nicotine cigarette makes little sense to me.
>>XXII also has a high-nicotine cigarette, the argument being that if the nicotine high is satisfied with one cigarette, then the amount of tar going into the system will be reduced, because one will be smoking less.
I agree on that too, but then how is that better than an e-cigarette with no tar at all?
>>There are questions of oral fixations here
Again, potentially solved by an e-cigarette.
The ultimate driver is the nicotine, but it reinforces all sorts of secondary habits too.
>>XXII
My own take is that this is a misguided idea. Cigarette smokers are addicted to nicotine, not to smoking, and the fundamental harm comes from the smoking itself not from the nicotine. The history of low-nicotine cigarettes is that smokers puff more vigorously to get their normal fix.
So from my perspective e-cigarettes make much more sense - deliver the nicotine without the more harmful aspects of smoking.
I have no idea what the FDA will do with this concept other than a belief they will be very cautious indeed.
Peter
>>I presume you meant to say, somewhat better.
Correct. Thanks for noticing.
Peter
>>This has been a trend from public biotech companies in recent years: release incomplete data by self imposed timeline rather than when data are ready.
Note this produces an inherent bias. If the data to date is not so good, the company is incented to hold on to it and wait for better outcomes when more data is in; if the data is good then they release it. Thus, on average, the early data is likely to be somewhat worse than the final data.
>>Difficulties in securing company's debt.
Enough said on the quality of this article given the company has a very healthy cash balance and zero debt.
My second set of answers to RBC questions are here:
http://www.siliconinvestor.com/readmsg.aspx?msgid=30916632
My post related to FGEN China:
Here is my response to the first two RBC questions relating to China:https://t.co/O8H7dXTp1F
— Peter Suzman (@Biomaven) January 2, 2017
China alone easily justifies current MC$FGEN
As a side note, some beta-blockers (like propranolol) penetrate the BBB easily while others do not. But this property seems to make no difference for migraine prophylaxis. Nobody seems to understand why though.
>>photodynamic therapy for prostate cancer:
Note the placebo here "caused" 3 heart attacks:
Photodynamic therapy is safe, effective treatment for low-risk, localised #prostate #cancer https://t.co/SocK5bESVh pic.twitter.com/4w48xOWtic
— The Lancet Oncology (@TheLancetOncol) December 20, 2016
>>CHMP conditionally approves Roche’s Alecensa for ALK+ second-line* NSCLC
From a purely medical perspective, it is close to malpractice to use this drug only second line. Much better to use it initially instead of first waiting to develop brain mets on Xalkori.
>>AKBA
And even if things go well for them they would likely only be third to market (after FGEN and GSK).