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>>The key then will be who can lock up the remaining large API suppliers via supply exclusivity agreements
But short-term that will be in competition with other generics, so no big bucks to be made. And long-term as other suppliers arrive, also nothing much to be gained. So there's no big win to be had here, except maybe for the first-to-file ANDA holder - anyone know who that was? (If I recall there was a fuss about the initial ANDA filings as the FDA initially maintained only a 3-year exclusivity that was subsequently revised to 5 years). \
I assume folks have seen this:
https://www.markmanadvisors.com/blog/2019/12/3/can-amarins-patents-protect-vascepa-from-generics
>>Patent that is invalid means anyone that wants to produce and sell can do a generic do so.
So what's in it for Dr Reddy? If they invalidate the patent then there is a free-for-all and nobody makes much money. If they settle, I assume Teva's settlement included a provision that gives them the benefit of a more favorable settlement as well, and so so again no big bucks for Reddy. So why spend the money on litigating?
>>I presume the two constituent agents are not directed against the same receptor.
One (agonist) crosses the BBB, the other (antagonist) doesn't, mitigating peripheral AE's.
>MRKR
It's hard to judge these results in a single-arm study - a lot of AML patients do well after a successful transplant. And AML patients are so varied that it makes single arm studies like this harder to interpret. (But I haven't looked at detailed results).
Know of any other small PBM's where this shoe hasn't yet dropped?
I suspect that they didn't properly align the HR confidence interval with the required 0.02 significance level.
That mismatch sometimes seems to be a thing:
Sales are distorted for all the new migraine drugs because of the extensive freebies all the companies are offering.
Said freebies do not apply to anyone on a Medicare or Medicare Advantage Plan though - those prohibit any discounts.
Ajovy was a bit late to the party, which started without it, and also does not offer an autoinjector.
Looking at the slide, that does not appear to be the case here - looks like just run-of-the-mill K-M censoring.
No, censoring is normal in any Kaplan-Meier curve - it just means they haven't followed the patient for long enough yet (and there has been no event with that patient).
Thus if a patient started the trial only the day before the date of the graph, they would be shown as censored after 1 day.
(Remember K-M graphs pretend everyone starts the trial at the same time).
You can read more about it here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932959/
>>GSK essentially got out of oncology in 2014
The deal only closed in 2015, and so this looks like a ridiculous major U-turn in just three years for a big pharma. Incoherent long-term strategy from where I sit.
Changing absorption of statins is a more plausible MOA.
In the previous AMRN trial the FDA AC briefing commented on a similar rise:
"During the review of the MARINE data, the Division noted that several lipid parameters (including TG) increased from baseline to week 12 in the placebo group, treated with mineral oil. The available literature regarding potential effects of mineral oil was considered. Similar increases in TG levels observed in the placebo groups from the Lovaza (omega-3 EE) clinical trials of hypertriglyceridemic patients were noted, and these trials did not use a mineral oil Because no strong evidence for biological activity of mineral oil was identified, ultimately it was concluded that the between-group differences likely provided the most appropriate descriptions of the treatment effect of AMR101."
These changes were over a 5-year period, and were accompanied by a decrease in triglycerides. Could easily be the natural course of the disease.
The changes in the placebo group were of a much lower magnitude than the favorable changes in the drug group.
>>The global erythropoietin (EPO) drugs market size was valued at USD 7.4 billion in 2016 and is expected to witness CAGR of 11.5% during the forecast period. Increasing incidence of chronic diseases such as end-stage renal diseases, cancer, and HIV is expected to accelerate demand for EPO-stimulating agents as these diseases may cause anemia. To curb rising incidence of anemia, demand for erythropoietin drugs is expected to increase over the coming years<<
If FGEN results and pricing are as I expect, the above is delusional.
>>VK5211
I really don't understand why you see this as a fail. It's incomplete data from a small trial, but nothing they disclosed to date gives cause for concern. You ask about the dogs that didn't bark (like lipids) - that is indeed a legitimate concern, but we have to wait for more data before deciding one way or the other.
This is designed to be a more selective anabolic drug, so there is no reason at all to believe it would do better than a conventional steroid on efficacy. So the fact that the durability wasn't 24 weeks is to be expected based on oxandrolone also not being durable at 24 weeks. Why you conflate that lack of durability with androgen induced hypogonadism I'm not at all sure.
What endpoint the FDA will want is unclear to me. 6-minute walk would be great - very likely they could get efficacy there if the trial was bigger. Fractures would be harder - need a way bigger trial. But FDA going to want reassurance on safety (prostate cancer for one), so this will require a fairly big study anyhow.
So the label on the three approved drugs is all very similar. The Teva version the only one that does not have an autoinjector.
AMGN the only drug with a non-injection site AE on it's label - constipation at 3% with their higher dose, but as I've mentioned previously seems to be more reported much more often than that. (It's a plausible side effect as CGRP does have a known impact on gut motility - seems to be a defensive mechanism to speed up motility after ingestion of something noxious).
Lilly being very aggressive here with 12 months free. They (unlike AMGN) got Massachusetts right and it's free here too unless the current law is changed in 9 months.
Peter
That seems on the unfair side. It's a top line result, and AMRN reported in the standard level of detail for that. Given a top line result, relative risk reduction is the more appropriate number.
The ITC case is really one-of-a-kind - no way to predict what will happen. More details here:
https://www.raps.org/news-and-articles/news-articles/2018/7/update-on-the-amarin-itc-case-and-the-issues-at-st
If they lose with the ITC, they have other venues (patent infringement for example) where they could proceed.
Be very surprised if they don't raise money here.
On pricing, let's wait for the detailed data to better understand the effect of the drug.
Peter
>>overdose of Saturated fats
Light liquid paraffin - the placebo used here - is not absorbed. Used primarily (in larger doses) for treatment of chronic constipation in children.
The FDA did raise and then dismiss the issue of it being a nocebo in the prior briefing documents.
Same price as Aimovig, and they have a once-every-three-months label as well as a once-a-month. But no self-injector.
FWIW, Aimovig has a listed 3% (for high-dose) constipation AE, but seemingly half of the patient reports online mention this as an issue. There is a plausible mechanism - CGRP is released in the gut in response to toxins and serves to increase motility.
Peter
I disagree on this - the situation is different when there are already approved drugs in the class. Then it requires a determination by the agency that the prospective drug might have better efficacy or safety.
I'd note that GLPG's drug did not get fast track.
Given the likely efficacy of pam is in the same general ballpark as the existing drugs, BTD was always a long shot for this indication. Let's see if it's still on the cards for pancreatic cancer.
FGEN has another pipeline HIF-1 drug that would be better suited to post-MI treatment. In that context you want to upregulate VEGF, for example. But they haven't talked about it in years. Some of that is a general decision to publish less and some is simply a focus on their two late-stage drugs.
>>Yes, that's the reason the imbalance exists, but it's not a reason to ignore the imbalance in assessing efficacy.
Agreed. What was the story behind this halt for this particular dosing group. 2014 has dropped off the bottom of my memory stack. :)
Is this the reason for the APOE4 imbalance?
>>This still doesn't explain why the sum of the parts can't be valued properly as part of a diversified company.
There are several possible arguments:
1. Complexity - analysts and the market don't do a good job of separately valuing the parts given they have different margins, different risk profiles and different expected durations.
2. Holder preferences - you are forcing a GSK shareholder to have holdings in what amounts to two different sectors. In theory you get a better fit by allowing each potential holder to tailor their holdings to their own particular preference. (In Modern Portfolio Theory lingo, the fixed combination might not be on the efficient frontier).
3. Management style - you really need different types of managers for the two very different areas.
On a more interesting note, I've always been extremely impressed with GSK chemistry capabilities. Whenever I've looked at a particular field GSK often seems to have the best initial compounds. But somehow their good stuff seems to get lost in translation, so to speak.
>>, the patients in this trial have metastases in such organs as the kidneys, but not the liver.
I believe it is the other way around - they have mets only in the liver. This is a known disease entity:
Wonder how much this will impact GILD?
So if I expect Keytruda to be a $10 billion product, does that justify aggressively buying MRK? I have no clue on the valuations of these big pharma - when I take a superficial look at the numbers the stock doesn't look that cheap.
Peter
>>concerned about what NKTR/BMY are doing in NSCLC
I haven't kept close track of NKTR (no position previously, although I bought a little yesterday as a trade) - could you explain this further?
>>This again points to mistake TRIL made by declaring MTD with 1st sign of DLT
Agreed. But in their (limited) defense, 47 initially had something close to a 3 year lead and lots more money.
Their data is indeed good - better than TRIL's except for what TRIL has shown in CTCL. I was indeed surprised that they were able to overcome the antigen sink so well and increase dose so much.
Let's see what TRIL is able to do now that they too are increasing the dose more aggressively. We should get some data at ASH. I'll be particularly watching CTCL and PTCL.
Likely the FTSV IPO will be on the hot side.
Peter
>>Musings on today's NKTR selloff
>>But the NKTR-214 data in melanoma/RCC/UC are ok (IMO) despite lower ORR in (early-look) Stage-2 cohorts.
But what do you make of the twitter comment by JQ in the thread below noting that in the first trial there were very few additional responses after the first scan?
A couple good data points on biomarkers via Priti Hegde, Director of Biomarkers at Roche.
— Brad Loncar (@bradloncar) June 4, 2018
PD-L1 prevalence and ORR segmented by TMB from lung cancer studies. pic.twitter.com/bgc5Vir2HL
>>How would regulators treat a drug that short-term may increase the risk of death but for a subset significantly increase survival?
With great difficulty.
>>Finally, just as a related note: being stat sig OS resected vs unresected AND stat sig more resected is no guarantee that the HR is even the right direction overall. All depends on how the survival curves cross.
Agreed. But strong likelihood that prior to resection deaths are roughly equivalent, and pam has a placebo-like AE profile.
In locally advanced pancreatic cancer, there is essentially a 100% death rate within 2 years absent a successful resection. So if the FDA doesn't agree to successful resection as an endpoint, then maybe the best endpoint would be alive at 2 years post diagnosis.
>>HR=0.92.
I would like to make a general point about HR's in these IO drugs. It is my belief that the stated HRs understate the benefits of the drugs. The reason for my claim is that these PD1 drugs violate the proportional hazards test - you see an initial steep K-M curve and then the PD1 arm flattens and separates. Thus there is late benefit - but the normal statistical tests don't reflect this properly.
To take an extreme example, imagine a disease that is uniformly fatal in say 2 year, so K-M curve is a straight line. Now imagine a drug that cures say 20% of people after 1 year on treatment. So the curves will be identical for a year, then a shallower slope for another year, and then a flat line. So if you run the trial for say 2 years, the HR will be miserable, but the drug is clearly doing something. If you compare the numbers reaching say 2.5 years you will see a big difference.
This same analysis is incidentally relevant to $FGEN's pamrevlumab in pancreatic cancer. You might see stat sig increase in resection, and a stat sig increase in OS for patients resected, but still not see stat sig on an ITT basis.
Comments welcomed.
Hard for me to see these results being competitive with the PCSK9s.
Peter
I don't really follow the stock, so didn't listen to the call. The liver elevations on closer examination are only a modest signal, but the issue is the FDA has been bitten on prior liver issues with antibiotics so they might be a bit gun shy.
>NBRV
It's not the stools - it's the liver enzymes. Potentially a serious concern.
>>Not true for most injectors, who bunch their Botox patients’ appointments in close proximity to reduce or eliminate wastage.
They may do that in practice, but I believe it's actually illegal - I've seen warnings against doing that. Technically they are supposed to bill for 200 units and document the balance as wasted.
Peter