This is a topical small molecule sodium channel blocker. It just failed a Phase 2 for OA of the knee, which doesn't seem its most likely target.
Teva Pharmaceutical Industries Ltd. (TEVA) (TEVA) and Xenon Pharmaceuticals Inc. (XENE) reported today top line results from the double-blind, placebo-controlled Phase 2b study designed to evaluate the safety and efficacy of topically applied TV-45070 (4% and 8% w/w ointment) in patients with chronic pain due to osteoarthritis (OA) of the knee.
TV-45070 is a small molecule inhibitor of the sodium channel Nav1.7 and other sodium channels, including those that are expressed in the pain-sensing peripheral nervous system. Results from this trial showed that TV-45070 4% and 8% did not demonstrate statistically significant difference from placebo in efficacy endpoints of reductions in pain due to OA.
"While we are disappointed that the Phase 2b trial top-line results did not indicate efficacy in OA, Teva and Xenon have always been committed to a broad development plan for TV-45070 in both nociceptive and neuropathic pain," said Dr. Simon Pimstone, Xenon's President and Chief Executive Officer. "The Phase 2b trial in PHN being conducted by Teva is progressing as planned, and we look forward to seeing top-line results from that trial in the second half of 2016.
The Phase 2b osteoarthritis trial of TV-45070 was a randomized, double-blind, placebo-controlled study conducted at approximately 40 clinical sites across the US. There were three arms in the study and a total of 389 patients were randomized on a 1:1:1 basis: experimental TV-45070 4% administered twice per day; experimental TV-45070 8% administered twice per day; and placebo comparator (matched ointment without TV-45070) administered twice per day. Patients were eligible to participate in the trial if they were 40-85 years of age, had primary OA in a single knee (target knee), and met pre-specified visual analog scale (VAS) pain scores and were otherwise medically healthy. The primary endpoint of the Phase 2b trial was to evaluate the efficacy of four weeks of topical administration of TV-45070 (4% and 8% ointment) compared with placebo
AF confirms in article today. Search for "MannKind's Afrezza Lags Behind Biggest Failure in Inhaled Insulin". I wonder what sort of alternative universe the Manniac's live in.
NVS buys Spinifex for $200M plus up to $500M if drug is successful.
Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 receptor (AT2R) is a new target for neuropathic pain. EMA401, a highly selective AT2R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia.
In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22–89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22–28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987.
92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores −2·29 [SD 1·75] vs −1·60 [1·66]; difference of adjusted least square means −0·69 [SE 0·25]; 95% CI −1·19 to −0·20; p=0·0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo.
Two years for a NKTR-214 Phase 1 wouldn't surprise me. There are a lot of moving parts. I think it will go beyond the typical search for maximum tolerated dose. It will probably be evaluated against several different types of cancer. NKTR-102 spun its wheels against colorectal, ovarian and breast cancers, now it appears brain cancer/mets may be the best target. The company doesn't want to go through that again. In addition, combining NKTR-214 with another drug may be the path forward. That requires additional study and analysis before a Phase 2 is launched.
BIIB has the sodium channel blocker pain reliever CNV1014802, which they acquired when they bought Convergence. CNV1014802 has successfully completed a Phase 2, which puts it a couple of years ahead of NKTR-171. Haven't seen a Phase 3 announcement yet.
Two years for an oral Relistor competition seems about right. It's going to take months to organize and train a sales team, and get a marketing campaign going. In the best case, I don't see an oral Relistor launch before the end of 2016. One advantage the competition will have is that physicians and patients should already be somewhat familiar with oral PAMORA drugs because of the trailblazing by AZN. They can piggyback off of AZN's educational and advertising efforts.
Merrill removed all their research analysis of BLUE, because they were one of the financiers.
Sales and profitability are what is important. Passing Phase 3 and getting no sales is worthless. Ask former DNDN shareholders. How is Afrezza doing? Big pharma isn't immune, how did Exubera do for PFE?
There are two things that big pharma does better than small, in my opinion. The first is targeting the drug to the appropriate patient set. I think if NKTR could do things over knowing what they do now, NKTR-102 would concentrate on brain cancer/mets rather than OC and general MBC. The panitumumab Phase 3 had very focused entry criteria. The second is not pushing through every drug that has a chance of succeeding in Phase 3. It appears that MRK has put a hold on bevenopran (MK-2402). SP-333 and Linzess could be future competition in a crowded OIC space, and they would have wider indications than just OIC.
OK, I'll bite. Exactly what is the "sleight-of-hand" you mention?
If you are attempting to compare it to BEACON, there is one important difference. The panitumunab study met its primary endpoint. BEACON didn't. Doh!
Time passes faster than you think. The NKTR/AZN deal for Movantik dates from 2009, almost six years ago. It's been over four years since HR announced the "go it alone" decision for NKTR-102. The NKTR-181 Phase 1 started in March, 2011, over four years ago.
Also OIC, IRWD's linaclotide (Linzess) is expected to complete its Phase 2 for OIC before the year is over. Linzess is occasionally prescribed off-label for OIC now. The OIC treatment field is likely to be crowded before the decade is over.
Plecanatide passed Phase 3 for chronic idiopathic constipation.
Which reminded me to look back on their SP-333 candidate. SP-333 passed its Phase 2 for OIC last November. We should look for a Phase 3 study initiation.
Plecanatide and SP-333 are closely related and have a mode of action similar to that of Amitiza.
Figure BLUE is collecting and analyzing cells for mutations for each patient during the transplant step. Wish they would share the results with the public. I assume that the data has been generally benign, given that the EMA appears ready to approve LV for beta-thal upon successful completion of current studies. But that is only an assumption on my part.
It's more than "three lousy patients". Bluebird has reported five additional beta-thal patients have been treated as part of the Northstar study. Two of them are considered cured (transfusion free), the other three were within the first two months after treatment and not yet evaluable. There is also one patient treated years ago with the prototype virus, also transfusion free and considered cured. At this point, all BT/SCD treated patients that have been identified are either deemed "cured" or too early to evaluate.
I'd love to ask questions on the Monday morning CC.
1. How are the Northstar (1100 series) patients doing? Are they all progressing as well as the HGB-205 patients you reported?
2. In the past six months, have any new patients been treated, aside from the one sickle cell patient reported in the PR? If so, what is their status?
3. Could you discuss the off target activity you have seen from the LV?
Latest data from SNSS at EHA.
Among the new data presented today are detailed results from the subgroups of patients age 60 years and older (451 out of 711 enrolled in VALOR) with late relapse (n=87) and refractory and early relapse disease (combined n=364).
Among patients with late relapse disease, overall survival (OS) and leukemia-free survival (LFS) were comparable between treatment arms. The complete remission (CR) rate was 57% and 28% (p=0.0064) and event-free survival (EFS) was 5.5 months versus 2.3 months (HR=0.65, p=0.0852) for vosaroxin/cytarabine and placebo/cytarabine, respectively. Thirty- and 60-day all-cause mortality among these patients was 11% and 18% versus 2% and 14% for vosaroxin/cytarabine and placebo/cytarabine, respectively.
Among patients with refractory and early relapse disease (combined n=364), a population known to have poorer outcomes, OS was 6.5 months versus 3.9 months for vosaroxin/cytarabine and placebo/cytarabine, respectively (HR=0.69, p=0.0008). CR rates in this population were 26% and 10% (p=0.0001) for vosaroxin/cytarabine and placebo/cytarabine, respectively. Among these patients, LFS was 9.7 months versus 5.5 months (HR=0.50, p=0.0424) and EFS was 1.7 months versus 1.3 months (HR=0.59, p LT 0.0001) for vosaroxin/cytarabine and placebo/cytarabine, respectively. Thirty- and 60-day all-cause mortality among these patients was comparable, at 10% and 21% versus 11% and 25% for vosaroxin/cytarabine and placebo/cytarabine, respectively.
That's the big unknown, off target damage. I'm sure that BLUE has been collecting data and that it probably has been shared with the FDA, EMA and the RAC. I *assume* that the data has been generally benign, especially since the EMA is ready to approve lenti based on not many more patients. I wish someone would ask on the CC's. It's what has me most concerned, much more than efficacy failure.