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ARRY:
What worries me about the MM data is that there was only a single response. Even if we take the optimistic view that the ARRY drug took a carfilzomib PR to a CR, then why don't we see any instances where it took a minimal response to a PR?
I really think the objective response rate needs to be higher than carfilzomib alone. I realize its small numbers and all, but still...
CYTK:
Admittedly there's not much to read into, but it's hard not to be skeptical of the results. For example:
OT:
Obesity drug coverage:
Compliance is the wild card. If people comply and finish their 6 month term, then the other triggers are pretty easy.
Nothing guaranteed, but these providers are undoubtedly projecting / modeling possible benefits of weight loss and how that could impact their bottom line. This may be the initial step in exploring that question.
INCY / secret JAK1
The drug is numbered 39110 and in the quarterly earnings call they said it was JAK1 selective over JAK2. They noted that they are going to pursue the same development path as Jakafi, so MF, RA and psoriasis.
But as you said, no data yet so nothing much to talk about.
BTH / CYTK:
Not much that I've recently seen regarding the drug's development. I'm still generally negative on the program.
Lilly / INCY Baricitinib presentation at ACR:
You can access the slides here. They have a rather large collection of response / MRI data in the slides, and all point to the 4 mg dose showing the max benefit while minimizing safety concerns. The phase III trials are underway or in late planning and seems relatively comprehensive, as would be expected of a big pharma. Regardless of tofacitinib approval, my impression is that the market is big enough to accommodate another JAK inhibitor and commensurate revenues. The phase III trials in underway / in planning are going to start yielding data in 2H14 to 2H15, so still some time until potential payoff.
Presentation
General overview of pro-inflammatory cytokine signaling as it relates to JAKs:
- IFN-gamma signals in SLE and myopathies (JAK1/2 dependent)
- IL-12 and IL23 signal in Psoriasis and IBD and are JAK2 dependent
- IL-6 signals in RA and asthma and is JAK1/2 dependent
- Phase II in Psoriasis is ongoing. Dose ranging study to complete in 1H 2013
- diabetic nephropathy trial is enrolling, with completion in 2013. Primary endpoint is reduction in albuminuria, secondary endpoint is reduction in urine cytokine excretion. This is based on observation of JAK2 upregulation in DN
- 3 phase II studies in RA:
- JADC (biologic naive and biologic experienced)
- JADA (biologic naive)
- JADP (ongoing in Japan, biologic naive)
- goals are to define efficacy - dose response curve as well as the minimally effective dose
JADC
- 4, 7 and 10 mg baricitinib administered once daily versus placebo for 12 weeks
- placebo is re-randomized to 7 or 10 mg baricitinib at 12 weeks; all others continue at same dosing until 24 weeks
At 12 weeks
- ACR20 (placebo vs 4, 7, 10 mg: 32 vs 52, 59, 53
- ACR50 13 vs 35, 31, 30
- ACR70 3 vs 16, 9, 10
At 24 weeks
ACR20 (4, 7, 10 mg) 67, 67, 72
ACR50 33, 37, 44
ACR70 26, 30, 28
- biologic exposed versus naive subset at week 24
ACR20 (biologic exposed 4, 7, 10 mg at week 24 vs biologic naive): 64, 73, 80 versus 79, 63, 70
ACR50 (biologic exposed 4, 7, 10 mg at week 24 vs biologic naive): 29, 45, 40 versus 38, 32, 45
- summary of these data for me is that they have the right dose and the drug is generally insensitive to previous biologic treatment which supports novel MOA and market opportunity
JADA
- assumption here is that dose above 4 mg wouldn't show increased efficacy
- placebo, 1, 2, 4 and 8 mg baricitinib for 12 weeks, at 12 weeks placebo is randomized to 2 twice daily or 4 mg once daily whereas others stay the same until week 24
- at week 24, entered into extension study wherein all but the 8 mg dose level were brought to 4 mg; the 8 mg dose continues on at 8 mg until 128 weeks max
- those interested can check out the slides as there is too much to describe so I'll refer only to the ACR70 at 24 weeks which was 10, 28 and 24 for 2, 4 and 8 mg respectively. Bottom line for me is that the 4 mg dose offers demonstrably better efficacy than 2 mg, and is equal to 8 mg... in other words they've found their dose
- the time course of patients showing a response appears accelerated at 4 and 8 mg versus the 2 mg cohort
- the MRI data also track the 2, 4, 8 mg ACR responses pretty well, although there are some pretty big error bars for some of the measurements. Nonetheless, for a trial with ~50 patients in each group, the trends are rather clear. It should be noted that 2 independent radiologists looked at the data, in a blinded fashion and in random order.
- morning stiffness, of the bad kind, reduced significantly for the drug treatment arms
- compared to placebo, the safety profile also looks rather clean
- they see dose dependent increase in mean HDL, and a flat increase in mean LDL; they contend that this increase is driven by no change in the number of LDL particles, but taht there is an increase in the number of large LDL particles, meaning the smaller, more atherogenic LDL particles are going down
- no difference in mean change in hemoglobin at 4 mg versus placebo, which is relevant because this is a JAK2 signaling pathway
- the phase 3 strategy is rather expansive and those interested should refer to the slides. Bottom line is that there should be a variety of trial results (4 in all, with a 5th trial offered as a long term extension) that come out, starting in 2H14
- 2 phase III trials with 4 mg dose, 2 trials with 2 mg dose
- patients with renal impairment in the trials will receive 2 mg dose
====
Q&A
- they have lots of prospective plans in the phase III trials to measure the cholesterol situation in detail... they think the cholesterol is going up partly because systemic inflation is going down, meaning less stress on the liver and therefore a bump up in cholesterol. In either case, it's something they're watching.
TSRX:
I really don't follow them at all.
But watching PYMX slowly muddle through these trials with different dosing regimens, I think it's quite clear that a larger partner would have had much more data sooner.
Antibiotic studies aren't necessarily that long in duration, so you can get a lot of work done in parallel. But if you're like PYMX and have to do all of these studies in series, *and* you're inexperienced in drug development, it's a big problem.
PYMX:
For me, the moral of the PYMX story is that antibiotic development requires larger companies.
These guys should have collaborated a long time ago.
CELGZ:
That's how I see it too.
For those not familiar, as per the SEC 13D, the outstanding shares as of June 25, 2010 were 40,403,162. Abraxis CEO owned ~82% of those shares.
If they get a survival label for pancreatic after April 1, 2013 (safest assumption), then the payout is 300 million, for a value of $7.42 (give or take a penny or two) per CVR. Stock closed today at 5.92, which is a 25% discount for an event that is 8-12 months out.
The other provision of the CVRs is that annual payments accrue on sales above 1 billion. What those may be over the life of the CVR is a wild card. The breakdown is as follows:
(i) 2.5% of net sales above $1 billion but less than or equal to $2 billion
(ii) plus an additional amount equal to 5.0% of that portion of net sales above $2 billion but less than or equal to $3 billion
(iii) plus an additional amount equal to 10.0% of that portion of net sales above $3 billion
- payouts (if any) continue until the end of 2025, and if they are above $1 billion for 2025, then annual payments continue until the earliest of: EOY 2030 or EOY for the calendar year wherein sales fall below $1 billion.
CELGZ
CELGZ:
CELG / CELGZ
I'm somewhat surprised the CVRs are priced pretty much a full dollar below their value if Abraxane gets pancreatic cancer approval.
If it got official approval within a year, they're currently trading at a 17% discount to their value. Survival advantages in pancreatic cancer aren't often turned away by the FDA.
Looks like abraxane significantly improved pancreatic cancer survival.
Data waiting for a meeting in January. Insert my repetitive rant about hurting patients just because you want a meeting presentation here.
Obesity / VVUS / ARNA
VVUS:
ARRY / ONXX:
ONXX:
ONXX:
ONXX CC notes:
General impression: Again, pretty boring from my perspective because the analysts are really just obsessed with where each and every vial of drug is going and whether there is a speaker’s bureau. I understand that they want these data for their sales projections, but … yeah. Not one question about whether or not Onyx any new candidates to emerge out of their pipeline (apparently not interesting to analysts) and very few questions on the oral form of the proteasome inhibitor (oprozomib), their only visible “pipeline” drug. That, and the overuse of the term “colour” during the Q&A is really painful.
Nexavar sales appear to have stagnated, and the development program is also winding down. They have two remaining phase 3 trials in thyroid and breast. Success in thyroid won’t make the impact that breast will, but at the least it’s nice to see the company is diligent in addressing possible markets, and accepting failure (eg. Nexavar in lung).
The Kyprolis development program is great in my opinion. They’re well on their way to accruing data for ex-US registrations, which will be material. The more exciting approach, from my viewpoint, is their aggressive pursuit of velcade. They already have one head-to-head trial and another that will be initiated next year. It’s risky, but I’m all for it.
General notes from the prepared remarks:
Kyprolis / Carfilzomib:
- 10% of third line penetration for kpyrolis, net sales of 19 million (orders placed and product received by clinic and hospitals; sell through method)
- Kyprolis Reimbursement: confirmed coverage from all 12 medicare administrative carriers; 70% of 167 million people insured in the top 67 commercial plans have confirmed coverage
- 3 ongoing global P3 trials with a fourth in front line to be initiated 1H13
-Relapsed / refractory: FOCUS trial enrollment complete; intended to support ex-US approval and to demonstrate survival advantage; planned interim analysis and this may be available 2H13
- ASPIRE: PFS endpoint; progression events slower than projected, so interim analysis now available in 4Q13 or later
- Began enrollment in ENDEAVOUR: Head to head of kyprolis (+low dose dex) versus velcade (+low dose dex)
- 2nd head to head against velcade to be initiatied in 1H13 in front line setting
Oprozomib (oral formulation of proteasome inhibitor)
- Completed additional formulation work and are introducing a new tablet form into the phase I
- Data at ASH in december, but on the old capsule formulation
Nexavar
- Phase 3 DECISION study in differentiated thyroid cancer data in 4Q12
- Phase 3 RESILIENCE study in advanced breast cancer: enrollment to complete 1H13
Stivarga
- 20-30K patients indicated for Stivarga mCRC label
- Expect Stivarga reimbursement from medicare and private policies
- Priority review Stivarga in mCRC in Japan and GIST in US
Q&A:
- Impact of subcutaneous velcade… no info to date, but they believe majority of market already using subq velcade so the penetration to date takes account of that formulation
- Testing once weekly dosing for kyprolis
- China nexavar revenue: for 3rd quarter, sales in china were 27 million versus 24.5 million in second quarter; 21.4 in 3rd quarter of 2011
INCY:
INCY CC Notes:
Net Impression: pretty boring conference call. Lots of talk from analysts trying to determine exactly how many patients are on the drug and exactly how many days they’re on drug, etc… etc… No company really answers these questions so it become tedious to hear analysts trying to pry this data away. Basically no talk about the pipeline, so that was disappointing.
Prepared Remarks:
- Old method of reporting sales was Sell Through method: measuring dispenses to patients. Now doing Sell In: Recognizing revenue when product received by the specialty pharmacy.
- Guidance $130-135 million for 2012
- 244 mill cash and investments, excludes 9.5 million in restricted cash held in escrow for interest payments to 4.75% senior notes
- Believe there is a shift to less advanced patients coming onto Jakafi, and docs are getting better acquainted with optimal use of the drug (physicians who modify dosing have better persistency / compliance rates than those who don’t)
- Working to identify patients who are good candidates to restart Jakafi after being taken off drug.
- Looking to modify FDA label to increase indicated population (mostly related to prior exclusion of patients with platelet counts < 100K)
- Response trial for polycythemia vera (PV): on track to complete enrollment around year end, sNDA in 2014.
- Relief trial for PV: looking for symptomatic benefit… not for approval but to support labeling claims
- Jakafi in pancreatic ph2 to complete enrollment by YE; data in 2nd half 2013
- Baracitanib: ACR presentation of 6 month data for phase 2b in RA
- Screening has begun for phase 3
- Lilly looking at psoriasis and diabetic nephropathy
- cMET and IDO inhibitor programs “progressing”
- 39110: trials for MF and RA and psoriasis (this is a Jak1/2 inhibitor but predominantly Jak1)
Q&A:
Jakafi:
- Will eventually provide survival follow up for Comfort1/2 to the FDA but don’t believe the label will be altered based on these data
- Seems much of the learning curve is depending on docs being able to properly titrate patients with low platelet counts (less than 100K) onto the drug… they believe they’re beginning to see improvements in this regard
- Of the total base of patients on drug in 3rd quarter, bulk were repeat patients, next largest were new patient adds, smallest proportion were restarts
- Reimbursement: 50% of patients are commercial, 30% are medicare, remaining are VA, military, etc…
- Majority on drug are intermediate-2 / high risk… now seeing some intermediate-1
Pipeline:
- 39110 is being put into the same studies as Jakafi to get data quickly
- Some talk about diabetic nephropathy: rationale is inflammation and increase in JAK levels in the kidney
- Baricitinib: not processed by liver as jakafi is (I was surprised to hear this)
Belviq:
VVUS / ARNA:
It's probably because I'm a crappy investor.
Also, the next time you post that laundry list of questions, you should probably remove the bit about the deformed babies. Belviq is contraindicated for pregnant women, and it's not because it makes them super moody.
Qysmia:
ARRY:
Multiple myeloma seems to be amenable to monotherapy. Do they have such a trial running or are they focused on combination trials?
Drug costs:
To me it's pretty clear that the companies are ramping prices when they can, to the maximum amount that they can.
From the Ariad investor day slides, the annual price increases for the three CML TKI's were:
imatinib: $2448 to $5819 in 7 years, or 13.2% per year
nilotinib: $5701 to $8181 in 3 years, or 12.8% per year
dasatinib: $4986 to $8181 in 4 years, or 13.2% per year
I'm not certain what exactly rationalizes the 10%+ increase per year, but increasing the share of profit has to be considered.
Company explanations that the drugs are priced based on efficacy would only explain the initial pricing plus annual inflation +/- a few percentage points for the cost of running the business. It doesn't explain why prices increase 10%+ per year since the efficacy of the drug doesn't increase annually. One could even argue that it becomes worse.
And the efficacy argument also doesn't hold when you consider that the changes in imatinib pricing are likely representative rather than exceptional. Yet when looking at efficacy, it's fair to say that imatinib is exceptional and not representative.
Understandably the companies require a profit motive, and there is a burden on the successful drugs of the portfolio to buttress the necessary R&D spending (and all of the losers that it inevitably tests and discards). However, with 13% increases annually, I don't think it's unreasonable to see society test ways in which it can tame the trajectory of costs.
OT:
If I'm not mistaken, most of the posters on this board do not have degrees in the biological sciences. And if we rated the top 2-3 posters on this board, I'm somewhat certain none of them would have had formal training in the biological sciences.
So let's dismiss with the opportunistic mentions of people's backgrounds and consider the content of their writing.
SRPT:
Sorry, that was very vaguely worded. When I say functioning, what I mean is the percentage of fibers that have dystrophin that is actually linking sarcomere function to sarcolemma*. So strictly speaking that would be a subset of the number of fibers that express dystrophin.
* note to SRPT... this word has two Ms
SRPT:
SRPT:
This guy appears to have ruffled many feathers regarding SRPT. His criticisms of the molecular biology / protein work presented by SRPT are valid. That seems to be setting off many of the SRPT longs who appear passionate about the topic. But I'm not quite sure what they're mad about: he's just analyzing the data.
The outstanding question for me is what percent of fibers really need functioning dystrophin in order for these kids to regain meaningful muscle force? It need not be 100%, but can it be as low as 20%? 10%? That threshold is important because the walk data, if verified, can't be ignored; yet the molecular data paint a less than encouraging picture for those driven by MOA considerations.
VVUS / MDVN:
Stolen off the Twitter from zbiotech:
Xtandi 16% NRx share in 3rd week vs Zytiga
Qsymia Rx up 3x wk/wk (1,455), insurance coverage of 53%, up from 35%
SRPT / RNAi Blog:
the blogger notes:
SRPT:
Nice that they showed the protein data.
The fiber immunofluorescence results look pretty good and quite clear. Whoever did the Western blotting needs to be ashamed of him/herself.
But honestly, the immunofluorescence and Western data do not look like they match at all. Given appropriate resolution, they should be seeing a lower band on the Western data which does not seem apparent at all.
In any case, good luck to these boys!
Of tangential interest to biotech investors:
Bob Lefkowitz and Brian Kobilka have won the Nobel Prize for Chemistry. Lefkowitz is, in a sense, a grandfather of the biotech field since he has done the pioneering work on the discovery and function of G protein coupled receptors over the last 30 years.
VVUS: