I will review and comment on this article when I have more time. But, from what I have seen just by perusing it, the author is clearly misinterpreting data, and intentionally misleading readers. For example, he states "no significance" on several findings - I'm not sure which planet he's from, but a p-value
Thanks for laying out your calculations. I think some on this board just throw out numbers without justification, whether high or low, and then ridicule actual calculated projections.
No one knows for sure yet what the cost will be, but I think people can easily apply various scenarios and discover what the baseline estimate might look like in terms of sales for the US.
A path toward approval in the predialysis population for a IDA/binder drug is great, regardless of whether they have to complete another trial or not. This would be a first!
Let me clarify, this is what I'm thinking...
The NDA for ESRD does not mention anything about indications for the predialysis population. The labeling language in the submitted NDA is strictly for hyperphosphatemia in ESRD.
The company is meeting with the FDA to discuss whether or not they need to conduct another trial to support label expansion of a 'potentially' approved product. I think the FDA will say existing data from the PII CKD study are sufficient for label expansion, contingent upon approval of the NDA for hyperphosphatemia. If the data are sufficient, then Keryx submits an sNDA (label expansion) following approval of the already-submitted NDA. If the data aren't sufficient, then they will go through another trial before they submit a supplemental NDA for label expansion. But, they can only submit that sNDA after a drug is already approved (I'm assuming the drug will be approved for hyperphosphatemia in ESRD).
If the NDA is approved by the FDA for hyperphosphatemia treatment, and the FDA allows existing Phase II CKD data to be used in obtaining label expansion, the company will then submit the sNDA (label expansion) for treatment of IDA in predialysis patients without ever conducting another trial.
If FDA says Keryx can obtain label expansion if they conduct another trial, then they will simply be submitting the sNDA at a later date (after trial completion). I think there is every reason to believe the FDA will allow label expansion; it's just a question of whether or not another trial needs to be conducted. I'm of the opinion that it won't be necessary.
For what it's worth, I think the FDA will expand the use of Z to predialysis CKD patients without another trial. If not, that's fine with me; off-label use will come into play regardless of the FDA's decision on label expansion requirements. The FDA should be looking at Z as an IDA drug in NDD CKD, not a phosphate binder drug. That makes a difference.
I would look to point out two important points with regards to the FDAs (i.e. advisory committee's) previous opinions regarding use of phosphate binders in earlier stage CKD patients. First, according to the most recent written opinions made by them, no data existed at the time to evaluate clinical benefits of phosphate binder use in predialysis CKD patients. Companies, i.e. Genzyme, Shire, and Fresenius, wanted to expand the labeling of their drugs, but the advisory committee commented that the "body of evidence around
phosphate binders in the pre-dialysis population was limited and inadequate to promote wide use in
the pre-dialysis population with modest elevations in serum phosphate." The majority of the committee voted in favor of extending use to predialysis patients with hyperphosphatemia; however, they unanimously agreed that further clinical studies were needed to characterize clinical benefits and risks. The three companies wanted to expand usage based on risk markers, but that would require outcome studies. The FDA has been reluctant to approve phosphate binders in the predialysis setting because they haven't proven to affect clinical outcomes; that's precisely what the FDA wants to see in this population. Perhaps the Japanese and EU simply don't require clinical outcomes to justify approval.
In walks Keryx with Zerenex, which doesn't need to make the same risk marker claims. There is no need for them to perform outcomes studies, because Z wouldn't be used to "prevent" clinical outcomes. It would be used first and foremost to treat IDA in the predialysis setting. If they were to say that the drug will be expanded to predialysis patients because it prevents the onset of 'x', then I would say that an outcomes study would be in order. I don't think Keryx is taking that route with Z in the predialysis setting. I think they will easily get expanded label approval because affecting hemoglobin levels are an approvable clinical endpoint.
The voting tonight is only to end the debates. If they don't receive 60 votes to end the debate, then debating will continue into tomorrow. If they get the 60 votes tonight, then count on voting on the bill itself tomorrow.
The only thing that happens tonight is a possible cloture vote to end the debates. The actual vote on the bill won't happen until tomorrow at the earliest , assuming they receive the 60 cloture votes to end the debate.
The more I read, the more confident I become about ACTCs ability to achieve marketing approval after a PII trial. I don't think there will be a need for a PIII. Imbruvica was approved based solely on PII results within 9 months of Pharmacyclics and JNJ announcing BT designation. I think ACTC will announce BT soon, complete dry AMD and SMD PII trials, and submit an IND for approval following data release. I'm betting they see approval in 2016.
Yeah, there's no doubt it meets all qualifying criteria for stroke.
I have been keeping an eye on all stem cell clinical trials; if a therapy improves upon what MSCs are capable of accomplishing, I think it's likely that Multistem will be working in stroke. We'll of course have to wait and see, but thankfully results aren't too far out.
I believe ATHX will be to market much quicker than some realize (and I'm not talking Japan).
There are currently three approved BT drugs, one of which is Imbruvica. Pharmacyclics and JJ were granted two BT designations for the drug in Feb. 2013 and in April 2013 based on PII data results for each trial (two separate indications). In June 2013, the companies filed a regulator application and were given a PDUFA date of February 2014. The companies received an early approval, in November 2013. So, within a year of announcing a Breakthrough Therapy designation, the companies had an approved drug - based only on PII data.
So, assuming ATHX receives BT designation for treatment in stroke by the end of the year, it seems possible that approval could theoretically happen in 2015.
You must be assuming a price tag of $1000 per injection... that's WAY below cost estimates that I have seen for the cells. I have seen the most conservative price projections at $5,000-$10,000 per injection, which equates to $14.5B-$29B in revenues if you estimate 10% market penetration of the 29.3 million dry AMD patients in Europe and US ( as of January 2014, published in Lancet, so these are updated numbers).
What's interesting is that the dialysis providers currently do not profit from Medicare Part B reimbursements. DaVita, for example, receives its profits from private revenue streams. Nearly 90% of ESRD patients are on Medicare, so that 10% is providing the vast majority of their profit. Being able to profit from the Medicare Part B reimbursement would be a first.
It is a sure thing; oral phosphate binders won't be integrated into Medicare Part B until 2016. Dialysis providers can simply claim that individual doctors are prescribing the drug for the benefit of the patients. Clearly, this could be the truth. Waste? You bet. But I don't think they can make modifications to the payment system in anticipation of a hypothetical scenario. Although that hypothetical scenario seems pretty likely right now.
For 2015, phosphate binders will NOT be bundled. Take a moment to think about what that means for dialysis providers for that year. A dialysis provider receives bundling payments to pay for EPO, iv iron, etc. Zerenex will be putting A LOT more money into the pockets of dialysis providers next year.
Also, consider this... even the cheapest phosphate binder available would not be saving the dialysis providers money in 2015, because it would mean that normal EPO and iv iron usage would continue to be paid out through a bundled payment method.
Of course, there are plenty of variables to consider in assigning fair valuation at this point, assuming approval by the US, Japan, and EU. For example, do we really know the extent of the market potential in NDD CKD for those three areas, and what kind of penetration we're going to see? There doesn't seem to be any precedent yet, so nobody knows for sure. I imagine the NDD CKD label extension for the US will most certainly be approved by the FDA based on what I have seen in the data. And obviously, we will know for sure for Japan 'shortly' and EU within one year. Some people have argued that with the fgf-23 results, the drug could be penetrating the CKD market quite substantially off label, far exceeding numbers for the anemia/hyperphosphatemia market in NDD CKD.
With that said, I still think it's important to evaluate fair valuation for various scenarios to be ahead of the game after approvals. If we take Ron's assertion that Z will be a blockbuster, then we are looking at a minimum 1B in sales. I don't know if he includes Japan in that calculation or not. If not, a fair valuation would be around $61 per share (assuming a 35% profit margin, 85M shares outstanding, and a conservative p/e of 15x). I think that would be the base scenario.
It seems to fit the profile of a candidate drug for bundle payment.