Moderator: "Will the FDA accept the European results to approve Arikace for CF?"
Lewis: "The FDA will not approve Arikace for CF based upon those results alone.
However, if we have positive NTM results, along with positive results from the longer term CF study due later this year, the totality of those results will set up an interesting discussion with the FDA for the appropriate label for Arikace."
1. "Positive NTM results"? Now confirmed.
2. "Positive results from the longer term CF study"? Now confirmed.
The unexpected efficacy in a clinically significant endpoint (NTM study) probably means the "interesting discussion" can't start until the FDA has ruled on the application for Breakthrough Therapy status.
There was a similar welcome delay in Europe.
Following the Q4 discussions with the EMA concerning a filing for NTM - Insmed guided that if the NTM results were compelling, the filing for CF scheduled for Q2 this year would be scrapped in favour of a joint CF / NTM filing in H2.
They were :-)
Utter tripe from you as usual.
Why don't you tell us more about how Arikace missed its efficacy endpoints and only hit its safety endpoints in the NTM study?
When (not if) the WHO recommends that Arikace take the place of the injected aminoglycoside in the current regimen for MDR-TB, that alone will guarantee Arikace generates a multi-billion dollar revenue stream.
Use in infections where injected aminoglycosides are not used unless the first-line drugs fail is a possibility. But as aminoglycosides are classed by the WHO as Critically Important Antimicrobials I suspect the WHO will want Arikace to be used only when other drugs can't do the job without serious adverse effects.
I noticed my post this morning where I outed him as fdaadvisor and rosemariecorbin didn't stay on the board for long :-)
I'd be prepared to wager serious money he was under the DELUSION he was fooling us all with the fdaadvisor id.
We'll know the mid-May position after the market closes today. I wouldn't be at all surprised to see it up by a million shares - as a result of the efforts of the usual suspects to nip in the bud any perception of momentum on the back of the additional Arikace data just released.
I wonder if the usual suspects will try to walk the share price down by more than $10 tomorrow? Ideally they'd need to drop the price to around $2.50 to be reasonably sure of engineering our delistment.
On a more serious note, I suspect our free-float-adjusted weighting within the index hasn't been adjusted since last July's share offering. If so, our current weighting would be based on a share price of around $10.
Anybody looking to make life uncomfortable for the Shorts could do so by running the share price up by a dollar or two tomorrow. The tracker funds would need to be holding a considerably greater number of shares for a weighting based upon $15 instead of $10.
Conversely, the Shorts could try to drop the price significantly lower tomorrow.
From the "substantial improvement" criteria for Breakthrough Therapy designation -
... The new drug added to available therapy results in a much greater or more important response compared to available therapy in a controlled study or to a historical control.
... The new drug has an important safety advantage that relates to serious adverse events compared to available therapies and has similar efficacy.
Intravenous amikacin is already approved by the FDA -
Amikacin Sulfate Injection, USP is indicated in the short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species.
In order to have approved IV amikacin the FDA must have on file extensive clinical trial data.
One would imagine a straight comparison between that "historical control" and the extensive Arikace safety data now available would establish "an important safety advantage that relates to serious adverse events" - the absence of the systemic toxicity which has historically caused damage to hearing and kidneys.
Insmed is already conducting a long term safety study in Cystic Fibrosis in Europe.
It seems to me the most likely outcome here is approval under the Breakthrough Therapy pathway for the treatment of -
"serious infections due to susceptible strains of Gram-negative bacteria" and mycobacteria
- subject to Insmed conducting a Phase IV clinical trial to establish the optimum period of therapy for mycobacterial infections.
Sputum culture conversion alone qualifies for FDA approval.
The FDA and EMA approval of Bedaquiline is particularly relevant - as Phase II culture conversion in a drug-resistant pulmonary mycobacterial infection was interpreted as "preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint" there also.
1. Culture conversion in the Arikace study of infection with drug-resistant Non-tuberculous Mycobacteria -
(in patients who had been on therapy for 168 days at the cut-off point for the latest presentation)
Arikace Day 84: 11 of 44 (25%)
Placebo Day 84: 3 of 45 (7%)
Arikace Day 168: 21 of 68 (31%)
Placebo Day 168: N/A (treated with Arikace after Day 84)
2. Culture conversion in the bedaquiline study of infection with drug-resistant Mycobacterium Tuberculosis -
a) Stage 1
Bedqlin Day 56: 10 of 21 (48%)
Placebo Day 56: 2 of 23 (9%)
Bedqlin Day 168: 17 of 21 (81%)
Placebo Day 168: 15 of 23 (65%)
b) Stage II
Bedqlin Day 168: 52 of 67 (78%)
Placebo Day 168: 38 of 66 (58%)
Bedqlin Day 504: 47 of 67 (70%)
Placebo Day 504: 37 of 66 (56%)
In both studies the comparison was SOC plus study drug vs SOC plus placebo. The Arikace study only accepted patients who had been resistant to the SOC for some time. The patients in the bedaquiline study were expected to be treatable with the SOC, hence the higher conversion rates.
SOC = Standard of care.
In the Arikace study the SOC was a three-drug combo of rifampin, ethambutol and either azithromycin or clarithromycin.
In the bedaquiline study the SOC was a five-drug combo of ethionamide, kanamycin, pyrazinamide, ofloxacin and either cycloserine or terizidone.
That was my main reservation - until I saw the details I shared in the initial post in the "Breakthrough Therapy" thread.
From the recent guidance -
[ The Company expects current cash balances will be sufficient to fund operations into 2015. The Company plans to provide additional cash guidance in the third quarter once additional discussions with the regulatory authorities have taken place. ]
[ In the case of NTM the barrier to effective treatment is in gaining access to the interior of infected macrophages ... IV amikacin is used to treat this patient population right now. You can't get enough amikacin into the lung through IV to successfully address this disease. ]
How can such a high rate of conversion to culture-negative - in patients, some of whom had remained culture-positive throughout two years of the curently-available treatment - not be viewed by the FDA as "reasonably predictive" of a clinical benefit over intravenous amikacin in the treatment of MDR-TB?
Lewis - "That's going to be a dialogue with the FDA. And frankly out of respect for them we will not be coming out with a comment on whether we're filing or not when we have the data release at the end of March. We're going to wait until we have had dialogue with them based on the data we have to inform where we go from here."
They'll be careful to avoid any guidance which might be read as taking the FDA for granted.
Thanks for the 'on top' Al.
Any Long who is uncertain as to the merits of Arikace as a Breakthrough Therapy should look at the criteria I posted - and imagine if he/she was making the FDA's decision and looking for an excuse to reject the application.
If anybody here has a few minutes to spare, what's the best argument you can come up with for Arikace failing to meet the criteria?
Some of the stuff in the documents filed by McKool was painful to read even for a layman. I noticed a couple of jaw-dropping bits in the ParkerVision objection to a JMOL -
1. [ Dr. Prucnal's testimony that the output of the mixer is labelled "baseband" or is part of the "baseband signal path" does not mean that the baseband signal is generated prior to the capacitors or that energy from the carrier signal is not used to generate the baseband signal. ]
Really? Not even when Dr. Prucnal explains that "BB stands for baseband, O stands for output ..." - and then confirms that the mixer "does, in fact, create the baseband"?
2. [ Because the assertions are contradicted by the evidence and no Qualcomm witness testified in support of these arguments or explained how this resulted in non-infringement of any claim, JMOL is improper. ]
The object was to debunk the Qualcomm assertion that there was no hard evidence of infringement. Reminding the Judge that nothing said by a Qualcomm witness could be interpreted as evidence of infringement was borderline incompetent.
I love those posts from the Genta board.
I hope everybody who objects to the disruption of the forum by the Delusional Half-Wit took a copy, so that they could remind him of how much he's lost through trusting to luck.
"The main benefit that liposomal amikacin has when compared to tobramycin is that the liposomal formula can be administered once a day."
Lewis last August -
"We're going to be the first treatment for CF that's once a day. Compliance is a major issue in this space."
"You might throw in Arikace frankly more frequently because patients are more likely to take it. And if you're getting to the MIC with once-daily dosing then you might rotate in the other antibiotics less frequently."
"You know this is really a pretty disruptive introduction into the CF treatment market, to have a once a day portable therapy."
The rate of market penetration of Victoza - an injection for Type 2 diabetics whose blood-sugar levels were not being adequately controlled by their first-line therapies - demonstrates perfectly what Lewis means by "pretty disruptive" -
Week / Prescription numbers
1 ......... 49
2 ......... 411
3 ......... 1,057
4 ......... 1,465
5 ......... 2,164
6 ......... 2,703
7 ......... 3,268
8 ......... 3,599
9 ......... 3,911
10 ....... 4,801
11 ....... 5,330
12 ....... 6,043
13 ....... 6,616
14 ....... 7,505
15 ....... 8,090
16 ....... 8,925
17 ....... 8,551
18 ....... 9,814
19 ....... 10,355
20 ....... 10,719
21 ....... 11,728
22 ....... 10,577
23 ....... 12,163
24 ....... 13,021
25 ....... 13,475
26 ....... 14,501
27 ....... 14,340
28 ....... 14,793
29 ....... 15,282
30 ....... 16,231
31 ....... 14,636
32 ....... 17,000
33 ....... 16,908
Assuming by Week 30 patients were collecting a 30-day supply, by Week 33 the convenience of once-daily dosing over twice-daily dosing had already attracted 64,775 patients.
Thirty months after the launch roughly 160,000 patients were using the once-daily regimen.
Fwiw the FDA was approving drugs on the basis of data from foreign clinical trials long before it got its new GAIN superpowers.
The analyst prices you rely on are not buyout valuations. They are nothing more than predictions of the share price in a year's time.
It does my brain in that anybody would actually believe an owner would sell a multi-billion dollar asset for a given price for the sole reason that the price is x% higher than the current share price. I suppose you would have argued when the share price was $4 not so long ago that $6 was a fair buyout valuation?
Here's a clue as to what happens in practice -
[ Is AstraZeneca "realistic in what it believes 'fair value' is?" Timothy Anderson, a pharmaceutical analyst at Sanford C. Bernstein, said in a research note Monday. "Projecting the worth of new drug pipelines is notoriously difficult, and drug companies and financial analysts alike are often wrong to the tune of billions of dollars, especially when going out five to 10 years. Drug development is just not that predictable."
AstraZeneca said earlier this month that it expects to achieve annual revenue of $45 billion by 2023 as an independent company.
The company, which has an attractive portfolio of cancer drugs, has repeatedly trumpeted the strength of its drugs in development, saying it is projecting peak annual sales potential of about $23 billion for those drugs by the end of 2023. ]
"Every time I tell ... my long position is up 200% in 2+ Years, he acts like a petulant 6 year old"