A common theme among the analysts is that NKTR-181 isn't competing against oxycodone or placebo, the competition is the various formulations of oxycodone and hydrocodone.
I think this is where the incumbents in the marketplace have messed up. The best opioid customers are the addicts, that's where the big profit comes from. The formulations out today try a little but not a lot to eliminate the addiction potential. I wouldn't be surprised if big pharma has run preclinicals on v-e-r-y slow release formulations but didn't try to bring them to market because it would greatly cannibalize existing sales. Now it's too late. NKTR-181 wins all ties because it can't be manipulated. NKTR has no product in the market to steal share from.
Fast track is paying off. NKTR has the FDA's ear and explicit direction on what is needed for approval. There will be no rejection due to inadequate study design. Ex US partner? Say Astra Zeneca.
What's more important than comparison to oxycodone is comparison to the current formulation of Oxycontin. But here, NKTR-181 also shines. Oxycontin still is no where close to placebo. This is great news.
On to the efficacy results!
OK, I'll bite.
- 118 NDA submission is dependent on the outcome of the FDA advisory panel review for SC Relistor. Add one month for AZN to complete the NDA data package based on the meeting results, then add two months for NDA acceptance by the FDA.
- 181 Phase 2 agree, expect Q3 top line results. That's the biggie for the summer.
- 102 OC keeps getting pushed lower and lower in the HR briefing slides. Almost certainly the company will be directed to run a well controlled Phase 3 structured like 102 MBC.
- AZN 119 preclinicals have completed according to HR's briefing slides. I expect a decision to proceed with the 118 NDA will also trigger the submission of a 119 IND. I believe that AZN only has the rights to one 118 combo and that NKTR can develop their own. I wonder if NKTR would be able to license development of combo treatments to other pharma.
TRINOVA-1. For fully and partially platform resistant OC. It met the primary endpoint, 34 percent reduction in the risk of disease progression or death. Full OS results not expected until next year. By way of comparison, the Avastin OC combo had 52 percent reduction in progression, but Roche chose not to submit it in the US because OS data were not statistically significant. Reiterates that OS is what the FDA is looking. Description of Phase III's from AMGN release below.
TRINOVA-1 is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study evaluating trebananib in over 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15 mg/kg of intravenous trebananib weekly plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off).
Other ongoing Phase 3 studies of trebananib include TRINOVA-2 and TRINOVA-3. TRINOVA-2 is evaluating whether trebananib plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by PFS in recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. TRINOVA-3 is evaluating trebananib or placebo in combination with paclitaxel and carboplatin in the first-line treatment of epithelial ovarian, primary peritoneal or fallopian tube cancer.
The most dangerous side effects from naloxone come from counteracting the effect of the opioids -- in the brain. NKTR-118 is a very large molecule and does not affect the brain. That's why pain scores didn't rise, opioid doses didn't need to be increased and withdrawal didn't occur during the studies.
I wouldn't call it CYA, but I do think the NKTR-118 safety results had an effect. Until then, all the FDA had for review was Entereg and an uncontrolled Relistor study.
The main risk to the NDA submission is whether the FDA will require a larger safety study before naloxegol could be approved. Unfortunately I don't think that AZN will submit the NDA prior to the FDA advisory panel meeting because it isn't clear what might be required. Payment to NKTR is upon NDA acceptance, not submission. The NDA data package needs to reflect what the FDA requires (preapproval or post approval study, REMS).
That said, AZN has a big advantage over SLXP. We're talking SC Relistor here, not the oral version. In addition, the SLXP sales force is focused on GI specialists, not GP's, orthopedists and pain specialists who will be the likely prescribers.
From the PR. I assume that the referenced "another peripheral mu-opioid antagonist" is naloxegol.
The FDA has communicated that it is convening the Advisory Committee for the following reasons:
•“The potential cardiovascular safety signal observed in the 12-month safety trial of another peripheral mu-opioid antagonist for the treatment of opioid-induced constipation in patients with chronic non-cancer pain raises concern for this class of drug products.”
•The RELISTOR “supplemental application contains only uncontrolled long-term safety data, and while there is no cardiovascular signal apparent in this data, the lack of a control population does not allow a definitive evaluation to be made to rule out a potential cardiovascular safety signal.”
• “FDA needs to provide consistent advice regarding the need for Major Adverse Cardiovascular Event (MACE) studies to applicants developing drug products in this class for this indication. For this reason, a broader discussion of the potential for cardiovascular events across the drug class is necessary.”
Looks like it was nothing more than a flash in the pan. For what it's worth, PGNX is also up this morning. Wonder if it was some rumor about OIC drugs. An AZN NDA or SLXP resubmission would boost the stock price for sure.
AVEO is a poster child for incompetent and unethical management. They ran the Phase III for RCC in eastern Europe, where effective cancer drugs are unavailable. That was to induce fast sign up. They compared tivo to standard of care Nexavar. Patients that progressed after Nexavar were given tivo, the experimental unproven drug. Patients that progressed after tivo were given nothing, even though there are other effective drugs. Patients who enter clinical trials are expected to get state of the art care, not experimental #$%$ then nothing. OS data was totally uninterpretable with this study design.
End result. Over half the rank and file gets fired. Management keeps their cushy jobs. They will probably get a bonus for cost cutting.
There are several blogs that write about Solitron. There is a recent update at one called Oddball Stocks. Judging from that, there will be at least a few retail investors attending the meeting.
There probably isn't much work on the naloxegol NDA package left to do. Submission hinges on discussion about safety with the FDA and EMA. Is additional safety data required? If so, would it be required before or after approval? If additional data is required before approval, I think AZN wants to know that now, not one year from now after the FDA panel vote.
HR has his shtick down, presentation was smooth as silk.
New data on NKTR-192 was presented. Plasma to CNS equilibration is 43 minutes. More importantly, efficacy appears to peak between one and two hours after ingestion (I assume, HR doesn't say). I don't know how quickly and long the competitive products like Percocet and Vicodin work for comparison.
My big problems with the presentation was with the NKTR-118 section, which HR put front and center. Absolutely no mention of the possibility of a CV outcomes study, which is what AZN is negotiating with the FDA now. At UBS, HR stated that such a study wouldn't be required before NDA submission. It would have been good to hear him either provide an update or reiterate that. Related is that cash flow discussion has fallen by the wayside. Once again, I think that HR just doesn't get it as far as what the investment community wants to hear.
CLVS got some PR's for CO-1686 in a Phase I/II against a type of lung cancer for which there is no approved treatment. The dosage in the study has yet to reach MTD.
There is a nascent movement to identify cancers by genetic pattern rather than by traditional histology and site. This ties directly into targeted treatments. It could provide an explanation of why some treatments fail in some patients and are spectacularly successful in others.
The marginal cost of measuring biomarkers is quite small compared to overall treatment cost. The BEACON trial is at the forefront of the movement. I wouldn't be surprised to see biomarker evaluation eventually become standard in all cancer treatment. Meanwhile, NKTR can use the information gathered during BEACON to help guide further development of NKTR-102.