I don't think that Dees taking time to take calls proves anything, but I do think it is suggestive. He would not be writing the BTD, but he would be reviewing drafts and providing input. The BTD application involves a lot of decisions as to operationalizing data collection for endpoints, presentation, and wording. I also think taking calls from shareholders is a way to make sure that you cannot be criticized for selective sharing of information if you are giving updates to large investors or potential investors. It proves nothing, but it is suggestive of good things. Diodia
According to Dees, PVCT has cited pain, infection, bleeding as examples of symptoms whose reduction would satisfy the FDA as clinically significant endpoints. Dees has said that a small bridging study might be done to "allow symptomatic endpoints to be prospectively correlated with objective response criteria." I feel confident that shrinking tumors will reduce pain, as it relieves the tumor pressing on other tissues. It may be that the small bridging study will not be needed, as they may have data already that shows this, if they tracked pain, infection, bleeding, etc. in phase 2 patients. The FDA needs "clinically significant endpoints" to give approval--shrinking tumors is not enough. But the endpoints PVCT says the FDA needs will be very easy to satisfy. As eckgar pointed out, "the criteria for BTD would require just one substantial improvement over available therapy!" I do not see how the FDA can deny approval, especially as Dr. Merrick Ross from MD Anderson is behind this, although as Dees points out, they can require an additional study.
The only negative scenario I have been able to come up with is that the FDA asks for a lengthy phase 3 study that costs $20 to $30 million, possibly with the motivation to allow nivolumab, lambrolizumab, or Roche’s MPDL3280A to get out their phase 3 results first, just to be paranoid here. PV-10 does a small secondary and everyone freaks out, while Adam Feuerstein does another number on PVCT as this is going on. This is obviously a short term scenario that does not affect the longer term value.
Maybe there is another negative scenario, but I have not been able to see it. Ruellia
He concludes that manufacturers may need to become more creative with patient assistance programs as combination therapies push regimen prices beyond $15,000 a month. The resulting patient out-of-pocket costs for those with a high coinsurance that ranges from 20% to 33%, for example, could be pushed beyond affordability, particularly with the chronic nature of treatment.
I believe that PV-10 will be priced at a time when managed care will be more active in cancer therapy than it is now, and the PVCT will be looking for a price advantage, and dtherefore at a minimum will price below $7,600. The big drug companies will be financially incentivizing doctors and hospitals to use their drugs, so PVCT will have to counter with pressure from insurance companies and hospitals reimbursed by diagnosis and looking for profit. Also PVCT is looking to market heavily in Asia including China and India, where lower costs will be important.
Of course, I really have no idea what PV-10 will cost. I welcome input from others on the board on this issue.
A separate Phase 1 study of nivolumab suggested that it is active in both Yervoy-naïve and Yervoy-pretreated patients. BMS has initiated two Phase 3 trials (NCT01721746/CheckMate-037 and NCT01721772/CheckMate-066 in Yervoy-pretreated and Yervoy-naïve patients, respectively) comparing nivolumab to chemotherapy to confirm the outstanding activity observed for nivolumab in the Phase I trial.
The Phase 1 results compared very favorably with Yervoy’s activity from its Phase 3 results (11% ORR and two-year survival of 24%). Nivolumab appears to have a better safety profile than Yervoy, particularly when comparing immune-related GI events.
There are high hopes for a combination of Yervoy and nivolumab. In a clinical trial, the combination yielded a 54% ORR with all responders achieving an 80% reduction in tumor volume. These near-complete responses strongly suggest that inhibiting PD-1 and CTLA-4 could be the next standard of care for metastatic melanoma though the combination resulted in a high rate of serious adverse events primarily those associated with Yervoy.
If the combination data are superior, the company will have to strongly consider the overall cost of therapy and potentially develop a creative patient assistance program. One key issue with the combination is that Yervoy is only dosed with four induction administrations, but nivolumab will be dosed continually until progression, potentially for longer than one year.
In other studies in advanced melanoma presented at ASCO, Merck’s lambrolizumab and Roche’s MPDL3280A, which not have yet reached Phase 3, showed impressive response rates in Phase 1 trials. At several doses, lambrolizumab produced a response rate of 38%; however, at the highest dose level (10 mg/kg) the ORR was 52%, including a 10% complete response rate. As with nivolumab, response to lambrolizumab was independent of prior Yervoy treatment. Roche’s MPDL3280A produced a response rate of 29% at several doses, similar to lambrolizumab and niv
My effort to make a conservative estimate for a monthly treatment cost of PV-10 of $5,000 is only a guess, but I used the following information about other drugs:
Yervoy: 4 injections for c. $120,000
Tafinlar reportedly $7,600 a month
Zelboraf’s approx $10,000 a month.
Mekinist priced at $8700 a month
Advances in Metastatic Melanoma Bring Price Competition, Redefinition of Value, and Likely Increased Payer Utilization Management
By Gordon Gochenauer, Kantar Health
He states that cancers have to date had little managed care attention, but with a plethora of new treatments and more patients surviving, managed care is now trying to push back on costs of oral therapies.
More available treatments and and their high costs, suggest strong payer management in advanced melanoma for the near future in a disease that has garnered little managed care attention previously.
Yervoy was a breakthrough drug, so it was priced high with a fixed regimen of four injections costing approximately $120,000. Yervoy increases median survival, but more important than its tumor response rate or median overall survival (mOS), is long-term disease stabilizations that led to unprecedented long-term survival of approximately 30% at two years and 20% at three and four years. However, severe immune-related gastrointestinal (GI) adverse events, can lead to costly hospitalizations due to diarrhea or GI perforations.
Yervoy has only a few years to enjoy being the standard immunotherapy. PD-1 and PD-L1 antibodies first made a splash at ASCO 2012, but longer-term follow-up data strongly suggest Yervoy will be replaced or serve as a combination agent. Farthest along in develop-ment is BMS’s nivolumab. In a large Phase 1 dose-finding study, nivolumab’s overall zzz response rate (ORR) was 31% across all doses, but reached 41% with a two-year survival of 43% in patients who received the planned dosage for the Phase 3 program.
I agree completely on the value and revenue potential of PH-10. There is a huge untapped market of unhappy suffering dermatology patients with no satisfactory treatment available. I can get to $40 a share for PVCT using assumptions regarding additional indications, and I think there will be many more than 100,000 monthly treatments. I just think that right now the decision is whether to buy at $1.86, assuming that you do not have so much that portfolio risk comes into play. Ruellia
I do believe that the dollar value of stocks is correlated to yearly revenue.. I agree that PVCT's revenue may end up much higher than my illustrative example, depending on how many indications get approved. My point is that the decision for an investor right now is whether PVCT is a buy at $1.86. If you think it gets approved and that 100,000 patients get treated, it is a buy. By the time it gets to $5, you will have a lot more information with regard to eventual indications and potential revenue to make a decision about buying vs. selling at that point. If you think that the FDA will not approve it, you should not buy. Diodia
let's just say that PV-10 gets approved by the FDA and 200,000 people, dogs, and horses per year have one monthly course of treatment of PVCT at $5,000 per monthly treatment. That would give us $1 billion annual revenue, with huge margins as PVCT is very cheap to produce. Let us say you value PVCT as two times annual revenue. That gives you a value of $2 billion and PVCT has no debt at present. Divide that by 200 million shares (to include warrants and preferred) and you get a valuation of $10 a share.
If you think PVCT will issue a big secondary after approval, then you will divide your valuation with a larger number of shares, and you will get a different share price.
It is easy to arrive at much higher valuations, but you do not need those to make a decision. For example, if you think at least 100,000 patients a year will get a $5,000 treatment from PVCT, you should buy at $2, if you are willing to wait until it hits $5. If you do not believe the FDA will approve it, or if you think PVCT will have to wait many years for approval to sell to those patients, then you probably don't want to buy. Diodia
I did "try to short" PVCT from my Fidelity account about a week ago, just to verify that shares were hard to borrow. Fidelity was willing for me to short PVCT but warned me that shares were hard to borrow and that there would be 25% interest. I did not complete the trade as I was bullish. Diodia
Thursday, January 23, 2014
I have really learned from and appreciated your posts, especially the ones on competitor drugs. I had a lot of the information on Yervoy and nivolumab and lambrolizumab from my due diligence, but you had a lot more! The info on Agarwala as an investigator for Yervoy was very welcome. AF must know this. I think his whole article was written in bad faith as was his Monday tweeting, as the blog CTD hints. Your calling his idea that no patients would be available for PVCT trials "guesswork" seems kind to me. I would call it "far-fetched." But we will find out before too long. Thanks for all the good info. Diodia
I loved your post and I gave it and your other comments further down a thumbs up. I hope all the best for your friend. Spending the hours that you do is amazing: real caring.
I felt much better knowing that MD Anderson is using PV-10. This validates that it does work clinically. I also think it makes it very, very hard for the FDA to say no to a phase 3 trial, which is all we really need at this point, if MD Anderson likes the drug and is using it.
Take good care of yourself, and we will all hope for the best. Diodia
What I was saying is that the 3 years of inaction was Feuerstein's one good argument. I specifically said I could not be sure that the problem was the patents. I am not a biochemist. But look at how the trading of PVCT changed after October 24, 2013. It is suggestive. Why would PVCT spend $20 to $50 million to prove a drug works just so that any other firm could profit from selling it? Even Feuerstein alludes obliquely to the patent problem for PVCT of using a 130 year old off-patent drug (Rose Bengal).
My point is that the "obselescence" argument is nonsense (and AF knows it), the "no patients available for PVCT" argument is ridiculous, and the comparison with Allovectin has no basis at all. All the rest of the article is just "OTC", "speculative," and other insults. Diodia
I trade oil stocks. The shorts love to go after micro cap oil companies with lots of debt and no revenue. The results for the shorts when a big well comes in are hideous. You can make a lot of money from a small company with no revenues if the prospects for future revenues are realized. But they never learn. Diodia
Feuerstein has one good argument in his article, that PVCT had said it was ready to go ahead with its phase 3 trial in November 2010 and had said that the FDA was on board. Then more than 3 years passed without any more formal trials.
I believe PVCT was waiting for protection through patents, and that getting its October 2013 patent was the trigger to move toward approval. But I can't prove AF's explanation (that PVCT was afraid to do more trials) is wrong.
But I feel certain that the FDA will not refuse to approve a phase 3 trial for PV-10 because it thinks other unapproved drugs, drugs with only phase 2 trial data (!) might turn out to be better, as AF claims:
"Given the huge advances in melanoma care today, FDA might be telling Provectus that it cannot proceed with the phase III study, as planned." This is ridiculous. The criteria are safety and efficacy, not comparison with other unapproved drugs, such as Nivolumab and Lamprolizumab.
In addition, his comparison of PV-10 with Allovectin's much, much weaker data is ridiculous as vandycommodores has shown.
I also think is nonsense for AF to say that PVCT will not be able to find patients because all the patients out there are already signed up.
The rest of the article is just name calling.
Let us say 100,000 people and/or dogs and horses receive PV-10 at $ 5,000 per monthly treatment. That gives you $500 million revenue. At a value of 1 x revenue, you have $500 M market cap, divided by 200 million shares and warrants, you have $2.5 per share, which is almost a 40% gain from here. So if you believe this very minimalist valuation, buying is a good idea.
Much higher valuations are very probable, but this is just for the sceptics. Diodia
and I believe that a fair number of warrants were exercised, so I bought some at $1.67. I am in wait and see mode, but I think PVCT is worth $340 million for the vet use of PV-10 and the dermatology alone.
I would really love to have the FDA minutes. Diodia