Other trial results which could raise PE would be Phase I dose optimization study for VX-970 and VX-803. These molecules are inhibitors of ATR and possibly ATM as well. ATR and ATM are cell cycle checkpoint initiators. Tumor cells damaged by radiation, cisplatin, gemcitabine, or etoposide can be rescued by DNA repair, which cannot happen if the cell cycle is allowed to proceed. If DNA damaged cells enter the mitosis phase, irreparable chromosomal break would occur. VX-970 and VX-803 inhibit the checkpoint initiator so that damaged tumor cells are not stopped before the entry into mitosis phase where the tumor cells would be mortally wounded.
for a few bucks instead of spending $300,000 for the side effects. Nobody is going to buy or fund this #$%$ no matter who approves Orscambi.
VX-661 will achieve an absolute FEV1 change of 3 - 4%, and we have to give a minimum PE of at least 30. So you may expect 5.76 x 30 =$ 173/share by then. If the second generation correctors in the [oven] are really good in treating 508del heterozygotes, a PE of 75 is possible.
The net the company will be reimbursed for Orkambi pill would be assumed conservatively to be 200 K per year. The list price will be much higher, and cannot be much lower than the price of Kalydeco. If the price of Orkambi were much lower than that of Kalydeco, the 70% Kalydeco taking patients who have 508del mutation would switch to Orkambi because Orkambi can improve the FEV1 change by another 4% for people with 508del in one allele and Kalydeco responsive mutation in the other allele.
There are about 20,500 homozygous 508del persons (12 years old or older) in US and major EU markets. For this year, we can count on 8500 persons in the US. In the Lum+Iva rollover study, greater than 90% of Phase III participants joined the trial. Uptake of this combo will be slower than the speed of adoption by 551 CFers, and let us assume that an average of 75 % of 8500 homozygotes take the combo within 6 months of launch (by the end of the year). You get a revenue of 8500 x 0.75 x 200 K x 0.5 year = 638 Mln. Vertex projects to receive 570 Mln from Kalydeco responsive CFers. The annual company expenditure will not exceed 1.1 Bln (source: Vertex), and the tax for orphan drug sales is zero. Then, by the end of 2015 the net will be 108 Mln (= 638 Mln + 570 Mln - 1100 Mln). This corresponds to $ 0.39 per share.
For 2016, 200 Kalydeco taking CFer will be freed from the VX-661 Phase III trial to raise the sales to 600 Mln, the US sales from Orkambi will be 1.4 Bln, and the EU sales will be 800 Mln. Adding all three, we get 2.8 Bln. If R&D and SG&A amount to 1.2 Bln then, we have 1.6 Bln. Subtracting 10 % royalty payment to CF Foundation, we get 1.44 Bln. Dividing this figure with the number of shares which will be about 250 Mln, the earnings per share will be 1440 Mln/250 Mln = $ 5.76 per share.
It's logical that 508/551 heterozygotes would have an additional benefit from adding a corrector like 661 to ivacaftor in improve further the FEV-1 and other clinical endpoints since these CF ;patients have partial expression of the CFTR on the cell surface and the folding transport defect preventing some of the CFTRl being trafficked to the cell surface due to the expression of the 508 mutation. The study you quote is the basis for the FDA allowing advancement of the Phase trials currently underway to treat these specific cf patients.
551D/ 508 shows 661 improves FEV1 by 4.5% over Ivacaftor proving Iva is not enough and correctors have a role. Also as I posted earlier Phase 2 Delta 508 F of IVC lost improvement in the follow up period from week 16-40 published in Chest. Sep 2012, Vol 142. No 3. Page 718-724. 120 patient cohort is not a small group in the study.
At what point would the negotiations for the pricing of Orkambi proceed with health insurers and pharmacy benefit managers? Is it in process now, anticipating FDA approval? Or must negotiations await actual approval? If so how long does it usually take for the drug price to get determined after actual approval? I imagine VRTX is chomping at the bit to get Orkambi rolled out!
A side question is also about labeling- is labeling negotiated as part of the approval process or is it decided after FDA approval?
Third, I just wonder on what you are basing your 5.5 pps estimates? Can you share with us your conservatiive calculations?
I wish you were right, but disagree. I think the FDA put too much of its credibility on the line by presenting such a ridiculous post-hoc statistical analysis and I think the statistician involved will want to "prove himself right" that ego will push the FDA to require a post-approval study. I think that will drag out the approval as Vertex tries to convince it otherwise. It might actually "help" some CFers though because the EU/AU/Cananda won't have it approved or available and would likely flock those trials in order to get open label after. I doubt any US CF Center's ethics committee would allow folks to be on only Kalydeco, though.
I also predict FDA is going to require 661 homozygotes to add a monotherap arm. And I predict that the residual function mutations which is not on label for anyone is going to be added as a 809 Phase 3 and that will have a mono label. I would do that since a sNDA will come much faster than 661 and residual function is not on label but they have proof of concept from 661 that it works!
Unfortunately no. Kalydeco does likely work alone some for df508 because there is some protein, albeit minor and differing by patient, on the cell surface, but it is only where there is protein on the cell surface from df508 on two allelles. One copy of df508 wouldn't have enough on the cell surface to have the same benefit (if it did, the combo would be enough for heterozygotes.) But the theory is sound and is why premarket crashed when FDA came out with its review in advance of the committee, but after the market players thought about it they said "oh, so Kalydeco alone works, what's the problem?" and then the market went up. So the homozygotes win both ways, but unfortunately not the heterozygotes.
It may seems to be negative to many but on the second thought if VX 771 can work independently as a potentiator for Homozygous and given 3% boost in lung function, which seems to be approvable to CF experts, then it will do the same for heterozygous i.e 3% improvement alone or with VX 661. So we have a drug Ivacaftor own by VRTX that will work all across CF, that is 70, 000 patients. CHECK MADE! Win win, no matter what?
Just as important is the future growth from the non-CF pipeline with flu and spinal cord injury drug
Phase 2 drug trials reporting next year, with the potential
to start Phase 3 trials for those drugs in 2016 as well. Then there is oncolocgy and preclinical candidates for CF HD and chronic MS all likely to either start or complete Phase 1 and 2 clinical trials over the next year as well. The potential for rapid growth of revenue and EPS is just starting to be realized. Once again patience will be rewarded for investors with a long term outlook .
The FDA said that it did show benefit. I thought that was the point of the FDA's cross study analysis. Listen, you're preaching to the choir here. I'm with you. I want approved and now. Just thought that part of the panels discussion was that this was a possibility. I couldn't see how either. Thanks for the response!
MNGA is now on the front page of major investment firms after announcing a major deal involving one of America’s top transportation companies.
at a cost of $300,000 per year per patient after 15 other patients dropped out of the study due to adverse side effects. Even worse is the 2 to 3% improvement quickly wore off.