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  • Anavex: A Regulatory Target Damaged By Incriminating Evidence  [View article]
    You are assigning too much importance to the grant. Foundation grants are nice but really have no bearing for future success. The grants are reviewed by MD and PhD reviewers so total BS is not funded but they don't have a crystal ball. The government still sponsors far more research through the NIH.

    Michael J Fox foundation is a great and ethical organization. They spend a large percent of their donations on research. Over the past 15 years, they have sponsored many projects, currently sponsoring about 90 a year. Getting a grant is great for the company as it is 'free money'....no dilution of equity and no future claims. However, getting a grant has no correlation with success. The majority (vast majority) of their sponsored research will not lead to a successful drug but will still hopefully advance the PD world. MJFF goal is to sponsor a variety of research. Sigma receptors is one of dozens of mechanisms. Most of their grants are to academic researchers but they also sponsor private company research. I found their summary in the database but not the amount of $$$. Given typical awards, likely 300-500,000.

    So, for a 6.00 dollar company with a market cap of 160 MM, this is worth 0.02 to 0.06 depending on size of grant.

    http://bit.ly/22yM00y
    Dec 30, 2015. 02:59 PM | 3 Likes Like |Link to Comment
  • Gilead: Trouble Down On The Pharm?  [View article]
    Approx. 25% of HCV patients have cirrhosis in US --- so 700,000 -1,000,000 have cirrhosis (US)

    1500-2000 of them undergo liver transplant annually
    Dec 7, 2015. 07:40 PM | Likes Like |Link to Comment
  • Anavex: Response To 3 Recent Bearish Articles  [View article]
    The study you referenced was a single test (Eriksen Flanker tes which s somewhat similar to Stoop test) in young people (average age 25) rather than multiple tests in elderly so is less relevant than the Oken paper I referenced.

    Dr. Maurice is clearly a well published and respected basic science researcher but he is not a clinical researcher so has no special personal knowledge about placebo effect in clinical studies. I pulled up one of his papers and noted he used appropriate controls in his mouse studies. Thus, in practice, he believes in controls and I doubt he would try to publish an uncontrolled study. He also is not without bias as he is on Scientific advisory board of Anavex. I'm not trying to imply anything evil, we all have our biases.

    I'm glad they are moving to a controlled study. I hope it is multi-site and recruits quickly
    Nov 18, 2015. 03:15 PM | 1 Like Like |Link to Comment
  • Anavex: Response To 3 Recent Bearish Articles  [View article]
    I believe there could easily have been a placebo effect in this study. The inclusion / exclusion criteria was MMSE score 16-28 according to clinicaltrials.gov.

    By convention, 18-24 is classified as mild dementia, 27 and higher is normal and 25-26 is borderline. I don't know if they have published the breakdown of MMSE scores at entry but it is likely that most subjects were mild (18-24), a few were moderate (16-17) and a few were borderline or normal (25 - 28). Mild AD patients function fairly well and many still drive. Having observed many demented patients from borderline to severe, there is no doubt in my mind that a mild AD patient could experience a placebo effect (whereas I doubt a severe AD patient could). Therefore, the lack of a placebo arm makes clinical interpretation of the study unreliable.

    Besides self-induced placebo effect, other things such as coaching, caffeine, time of day can affect a study when these are not controlled

    Here's a few references:
    Placebo effect on cognitive testing: http://1.usa.gov/1j6I4kx

    Effect of coaching on cognitive tests: http://1.usa.gov/1H7L7EX

    Time of day or caffeine and cog tests: http://1.usa.gov/1OPDKEG

    I look forward to the results from a real phase 2 with randomization and controls. Unfortunately the extended "2a" will add no meaningful efficacy data (though it does add some additional safety info).
    Nov 17, 2015. 09:41 PM | 1 Like Like |Link to Comment
  • Premarket Biotech Digest: Anavex Patient Comments, Focus On Science, Horizon Tumbles  [View article]
    I think they have enough reason to go forward with a real Phase II as discussed above. They have an interesting mechanism and a drug that appears to be well tolerated and likely reasonably safe. At this point, I think that is all they have because the study is designed such that an efficacy signal can't truly be separated from the random noise.

    Thus, I think that the hype and bashing are both unreasonable. Hopefully they will do a real phase II soon. If they have funds, the current data is sufficient to initiate that sort of study (i.e. placebo plus 3-4 doses with 30-40 in each group, multi-site, randomized and double blinded). Just because they are small does not mean their drug will not work (though statistically they have a higher fail rate than big pharma)

    Too often I see poorly designed studies by small companies over-publicized causing non-medical people to think there is much more to the data than there really is. Many companies do this. Though not a scam (in illegal sense), I feel that there is some ethical lapse in purposefully designing poor clinical studies and then hyping the results.
    Nov 12, 2015. 08:40 PM | 6 Likes Like |Link to Comment
  • Premarket Biotech Digest: Anavex Patient Comments, Focus On Science, Horizon Tumbles  [View article]
    Patients are Australian I think, so HIPAA would not be relevant. I have no idea if Australia has patient privacy laws and whether they might be relevant. In US, if patients agree (verbally and documented or in writing) to release information, this would probably be allowed.

    Regardless of the legal aspect. I think it is very suspect (desperate?) for a company to release any individual data from an ongoing study. I wouldn't touch this company.

    Sponsors can call a study any phase they want but, IMO, this is not a phase II study, more like a phase 1b multi-dosing one. I've seen many bigger phase 1 studies. Small biotech often performs crappy phase II's that are too small or too limited in duration to have any real meaning. Real companies do Phase II's that have predictive value. I've personally been site PI for several Phase II studies (all MS, not Alz) and every one had a placebo or comparator (against a standard of care) arm. They were also multi-site, double blinded and randomized --- how else could you determine what dose to bring forward into a very expensive phase III? Without these controls, the efficacy data is meaningless. Cognitive scores fluctuate and can be affected by time of day, practice effect, caffeine, sleep quality, coaching and cajoling. That is why placebo is needed.

    Hopefully the drug will work but all I see is that they have shown the drug will likely be tolerated and has no frequent safety issue. Now they need to do a real Phase II (i.e. multi-site, double blinded, placebo and a few doses with maybe n=120) to determine what dose should be carried into phase III
    Nov 12, 2015. 07:43 PM | 7 Likes Like |Link to Comment
  • Valeant - Is That The 'Smoking Gun'?  [View article]
    "For me the question is how did VRX get physicians to RX their drugs? Did the docs know that they were overpriced? Were the physicians incentivised and if so how?"

    Ted is right, most doctors are ignorant of the price of drugs and some (but not most) are ignorant about the price of their services.

    1. "how did VRX get physicians to RX their drugs?" There are many overpriced drugs out there offering marginal (if any) benefit over 4-20 dollar generics. Horizon is as bad as VRX and Endo, Mallinkrodt and Depo are not much better. I recall a recent pharmaceutical lunch with one of these. The discussion was all about the discount cards -- patients with private insurance would get the drug for no more than 25 (or something similar) dollars a month. When I asked at 3 different times what was the actual price, the rep would go back to price to patient of $25. Finally, the third time when I asked, she said she didn't know. What they are selling is (a) price to patient and (b) convenience to doctor as the card enrolls the patient into copay assistance. It is interesting that Medicare / Medicaid consider discount cards as 'kickbacks' to patients to incentivise and are thus not allowed.

    2. "Did the docs know that they were overpriced?". No. Case in point. Last week I looked in our drug cabinet and found samples of Duexis (Horizon ibu/famotidine), Vimovo (Horizon naproxen/esomeprazole) and Zelapar (Valeant, oral disintegrating selegiline). I asked a few of my partners at lunch what they thought the price was. They knew generic similar products were $20 or so for the 2 anti-inflammatories and they were low at 20-30 for selegiline (actually $70). They guessed around 200 for the anti-inflammatories (adding and they are only worth 50). They were shocked and outraged when they found out Duexis and Vimovo were actually $1500/month and Zelapar was $2000/month. One even commented if you write one script a month for one of these products with one year of refills, the pharmaceutical company gets almost as much over the year as the doctor.

    3. "Were the physicians incentivised and if so how?" I don't believe in any improper financial way (a couple lunches a year is standard and not motivating). The incentive was the product was marginally better or slightly more convenient (i.e. in case of Duexis 3 pills a day vs 6) and copay card makes it inexpensive for patient

    another interesting fact. Some patients feel that they are being disrespected if they are placed on cheap drugs. This type of patient feels that the more expensive drug is more effective (because in every other aspect of life, high price is better --- Mercedes vs. Kia or more prestigious --- designer clothes). Usually its the poorer patient (often with good insurance) rather than the millionaire who knows value.

    Those who think that companies like VRX and HZNP are just being capitalistic are wrong. The US healthcare system is all about moral hazard because someone else pays. Its a weird mix of pseudocapitalism layered on socialism. Does anyone really think that if patients had to pay $40,000 year for one glumetza a day vs. $48 for two metformins a day that anyone would choose the former?

    I'm not a big fan of PBM / insurers as our office needs to hire 3 people just to deal with procedure and medical pre-authorizations. However, they will place many more restrictions on parasitic pharmaceutical companies with products that don't add much value. Many large groups are becoming ACO's and will soon take on some pharmaceutical risk --- that will also lead to doctor's policing themselves against wildly expensive me-too drugs.

    The business model is broken for companies like this. Revenue growth will shrink or reverse. Valuation will follow.
    Nov 1, 2015. 09:52 AM | 15 Likes Like |Link to Comment
  • Horizon Pharma gets negative visibility over Duexis price; shares slump 17%  [View news story]
    There were 2 large phase III with about 1500 patients total. They only compared ibuprofen to Duexis (they did not include a third arm with separate famotidine and ibuprofen). These studies were likely appropriately performed and they did endoscopy so the studies were not cheap. As expected, the combo was better for the stomach than ibuprofen alone.

    Most doctors have had patients on combinations of Ibuprofen (or similar NSAID) and either famotidine or similar drug (H2 blocker (alternatively a PPI)) x many years. In fact, the first publication of taking an H2 blocker to prevent the gastric damage by NSAID's was from 1977! (cimetidine or Tagamet, the first commercial H2 blocker).

    This is truly a medication that is overpriced, adds very little to the generic option and does not make the world better. Is it worth 18,000/year vs 240/year just so patients take 3 pills a day instead of 6? Very few doctors prescribe this medication --- 44 million a quarter sales is only 29000 monthly scripts or 2400 annualized patients - a negligible proportion of chronic NSAID users. Insurance companies rightfully exclude this drug or put up formidable barriers (this compliment was tough to say as insurance companies can make my life miserable). Vimovo (naproxen/esomeprazole, also Horizon) is just as expensive and unnecessary. I don't think anyone in our group has wasted the healthcare dollar with either of these and I doubt these drugs will see appreciable growth.
    Oct 20, 2015. 03:50 PM | 2 Likes Like |Link to Comment
  • Archived GCVRZ Forum  [View instapost]
    From ECTRIMS

    Alemtuzumab slows brain volume loss over 5 years in patients with active relapsing-remitting multiple sclerosis with most patients not receiving treatment for 4 years: CARE MS I and II extension study

    F Barkhof, JA Cohen, AJ Coles, DAS Compston, M Filippi, EJ Fox, G Giovannoni, H-P Hartung, E Havrdova, S Schippling, KW Selmaj, DH Margolin, K Thangavelu, A Panzara, DL Arnold, on behalf of the CARE-MS I and CARE-MS II Investigators

    Summary: Researchers conducted this study to analyze the effects of alemtuzumab on changes in brain volume over 5 years in patients enrolled in the CARE-MS study program and ongoing extension study. They observed that a slowing of BV loss with alemtuzumab was maintained over 5 years in patients who were treatment-naive or had an inadequate response to prior therapy, despite most patients not receiving additional treatment over the previous 4 years. A reduction in inflammation may account for this durable effect on slowing BV loss, they postulated, as may the immunomodulatory effects of the distinct pattern of lymphocyte repopulation following treatment.

    Methods:

    For the CARE-MS studies, researchers enrolled patients with active RRMS (≥1 relapse in the past year and ≥2 in the past 2 years).
    Patients who had been randomized to treatment with alemtuzumab received 2 annual courses of alemtuzumab (12 mg) at months 0 and 12.
    In the extension study, conducted in 349 (95%) CARE-MS I and 393 (93%) CARE-MS II alemtuzumab patients, as-needed alemtuzumab retreatment was available based on evidence of disease activity, including relapse or magnetic resonance imaging (MRI) activity.
    At investigator discretion, patients could receive another DMT.
    Researchers performed MRI scans at baseline and annually thereafter, and measured BV loss via relative brain parenchymal fraction change.

    Results:

    In the extension study, 68% in CARE-MS I and 60% in CARE-MS II did not receive alemtuzumab treatment since month 12, and 2% and 8% received another DMT.
    In CARE-MS I patients, the median rate of BV loss decreased progressively over 4 years and remained low in year 5 (Year 1: -0.59%, Year 2: -0.25%, Year 3: -0.19%, Year 4: -0.15%, Year 5: -0.20%).
    In CARE-MS II patients, the median rate of BV loss progressively slowed over 3 years in CARE-MS II and remained low in years 4 and 5 (Year 1: -0.48%, Year 2: -0.22%, Year 3: -0.10%, Year 4: -0.19%, Year 5: -0.07%).

    ______________________...

    Saturday, October 10, 2015
    October 10—Alemtuzumab Reported to Keep MS Patients Relapse-Free Three Years After Last Treatment
    BY ED SUSMAN

    BARCELONA—The majority of multiple sclerosis (MS) patients treated with alemtuzumab (Lemtrada) did not require any further injections of the agent for at least four years, maintaining a relapse-free, progression-free status over that time, researchers said here at the 31st meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

    In the CARE-MS 1 trial, 369 patients received 12 mg of alemtuzumab by intravenous infusion at the start of the study and then again at 12 months. More than 90 percent participated in the extension trial and were monitored for five years on treatment, said Eva Havrdova, MD, PhD, a professor of neurology at Charles University in Prague, Czech Republic.

    If patients relapsed, they could receive additional doses of alemtuzumab or other disease-modifying agents, she said. The sponsor of the trial was Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals.

    Sixty-eight percent of the patients receiving alemtuzumab did not require any further infusions in the four years since the last scheduled treatment, Dr. Havrdova said in a presentation of the latest data. The low annualized relapse rate was maintained from year three (0.19) to year five (0.15).

    Dr. Havrdova reported that 70 percent of all alemtuzumab patients had no relapse cumulatively through years three to five; 80 percent were free from six-month sustained accumulation of disability progression through five years; and 33 percent of patients achieved a six-month sustained reduction in disability over five years.

    At five years, there was no change in the Expanded Disability Status Scale among the patients who responded to treatment, indicating their disease had stabilized.

    “These data illustrate that most alemtuzumab patients experienced sustained effects of treatment, despite the absence of additional treatment courses,” said Dr. Havrdova. "It is encouraging to see consistent effects maintained across multiple meaningful outcomes through five years.”

    Aaron Boster, MD, system director of the neurology MS program for OhioHealth Physician Group and OhioHealth Neurological Physicians in Columbus, told the Neurology Today Conference Reporter that the data on alemtuzumab sends a message to patients that their disease can be controlled. It also suggests that in a substantial number of cases, their disability can be reduced.

    Dr. Boster, who was not involved with the study, said he had patients who participated in the extension trial, which included those who had active disease despite treatment with other disease-modifying agents. He said he was impressed by the ability of alemtuzumab-treated patients to achieve the “no evidence of disease activity” status. He noted that more than 40 percent of the patients in the studies reported by Dr. Havrdova achieved that status after five years.

    LINK UP FOR MORE INFORMATION:
    ECTRIMS Abstract: Havrdova E, et al. Durable efficacy of alemtuzumab on clinical outcomes over 5 years in treatment-naive patients with active relapsing-remitting multiple sclerosis with most patients not receiving treatment for 4 years: CARE-MS I extension study: http://bit.ly/ECTRIMS-...
    Oct 11, 2015. 10:08 PM | 2 Likes Like |Link to Comment
  • Arena - A Deeper Look At APD-334  [View article]
    Here's the data from ECTRIMS regarding the drug BIIB just licensed with similar MOA as ADP334

    October 10, 2015Parallel Session 13:
    Late Breaking NewsResults of MOMENTUM, a randomized, double-blind, placebo-controlled, phase 2 trial with MT-1303, a novel selective sphingosine 1-phosphate receptor 1 (S1P1) modulator, in relapsing-remitting MSL Kapps, D Arnold, A Bar-Or, J Camm, T Derfuss, B Kieseier, T Sprender, K Greenough, P Ni, T Harada
    Summary: Researchers of this multinational, randomized, double-blind, parallel group, placebo-controlled trial assessed the efficacy and safety of the first phase II study with MT-1303, a novel selective S1P1 modulator in development for the treatment of relapsing-remitting multiple sclerosis (RRMS). The efficacy and short term safety profile of MT-1303 is encouraging, they concluded, and warrants further clinical development in RRMS.

    Methods:

    Researchers included 415 patients from 80 centers with RRMS (revised McDonald criteria), aged 18 to 60 years, and with evidence of recent MS activity were randomised 1:1:1:1 to receive oral MT-1303 (0.1 mg [n=105], 0.2 mg [n=103], 0.4 mg [n=104]) or placebo (n=103) for 24 weeks.
    The primary endpoint of the study was the mean total number of Gd-enhanced T1-weighted MRI lesions on monthly scans from weeks 8-24.
    Researchers conducted safety assessments in all randomized subjects.
    Results:

    In all, 381 patients completed 24 weeks of treatment.
    Researchers observed a dose-dependent decrease in the total cumulative number of Gd-enhanced T1-weighted lesions: 8.3 in placebo; 5.5 in the MT-1303 0.1-mg, 2.3 in the 0.2-mg, (median difference vs placebo -1.0 [95% CI, -1·0-0]; P=0·002), and 1.7 in the 0.4-mg groups (median difference: -1·0 [95% CI -1·2-0]; P < 0·001).
    The adjusted relative risk (placebo: 0.441, 0.1 mg: 0.436, 0.2 mg: 0.392, 0.4 mg: 0.103) was lower in the 0.4-mg group (P vs placebo=0.005).
    Grey matter volume loss was lower in the 0.2- and 0.4-mg groups (P=0·013 and P=0.002 vs placebo).
    Researchers found no clinically significant heart rate reduction at any MT-1303 dose, and the most commonly reported TEAEs were headache and nasopharyngitis.
    No serious adverse event was reported for more than one subject in any group.
    This study was funded by the Mitsubishi Tanabe Pharma Corporation.

    http://bit.ly/1R5SdcA
    Oct 11, 2015. 11:51 AM | Likes Like |Link to Comment
  • Arena - A Deeper Look At APD-334  [View article]
    ARNA's best chance to sell/partner ADP334 may be with either Abbvie or JNJ. They make Humira and Remicade, both used for moderate to severe UC. They have a trained GI sales force and long ties with physicians. Remicade (JNJ) generics are already available in EU and selected other countries and FDA has a biosimilar application from Hospira but has delayed a decision. Humira (ABBV) loses patent protection end of 2016 so generic could be available in 2017. Both of these companies should be interested in another UC drug and an S1PR drug could fill this need.

    60 million upfront seems low for MT1303. I presume existing data looks good or why spend anything. Probably with a good titration MT1303 had no cardiology effect. Biogen could quickly start a phase III for MS.

    I've owned ARNA twice in past. Today's drop was probably an over-reaction and I bought a small position at 2.60. They should be worth more than 620 million (215 cash; Belviq worth 200; 334 worth 150; rest of pipeline is worth more than 55). Maybe I'm valuing 334 too high. Of course when you throw in milestones and royalties, BIIB will pay far more than 60M if successful. 371 looks very interesting but way too early. On the positive side, the Phase I release may help stock price at end of year.
    Sep 9, 2015. 09:14 PM | Likes Like |Link to Comment
  • Arena - A Deeper Look At APD-334  [View article]
    I should have added this link to my comment above. RPC1063 has another 170 patients split between 0.5 and 1.0 mg in the MS phase II. In that study, "During the first 6 hours post first dose of RPC1063, maximum reductions in mean hourly HR were <2 bpm from baseline and no patient had a minimum hourly HR <45 bpm. No clinically-significant bradycardia or conduction abnormalities (AV block, QT prolongation) were observed, and HR and blood pressure were similar between groups across the 24 weeks. " The titration probably helped a lot. Actual patient experience with 170 patients is more valuable than 20-30 healthy individuals on the relevant APD doses. It looks like the titration with RPC1063 helped further. In real life, this is no barrier and we titrate with about half the med's.

    http://bit.ly/1JPcAZv
    Sep 7, 2015. 01:20 PM | 1 Like Like |Link to Comment
  • Arena - A Deeper Look At APD-334  [View article]
    Thanks for this link. I had not seen that slide in the past --- would have been a better slide for Arena to present in January. From the chart, in healthy volunteers, it does look like the APD data and RPC data (at least the 1.0 mg and below) are similar. AV blocks that would lead to a need for first day observation are unlikely to occur with a HR > 50. As I said above, I would expect efficacy to be similar. The clinicaltrials site shows the phase II will have 240 patients split between placebo, low dose and high dose. If they are able to replicate this safety finding in the larger UC patient population then they will have the data necessary to enter Phase III and try to snag a partner or buyer.

    They still will be 2 years behind so a successful safe Phase II will not be as valuable for ARNA as it was for RCPT, but it would help to get the market cap back to 2B.
    Sep 5, 2015. 09:59 PM | Likes Like |Link to Comment
  • Arena - A Deeper Look At APD-334  [View article]
    The half-life issue is moot. a 19 hour half life will almost always be a once a day drug. In fact, in the phase II MS study, RPC1063 was given at a dose of 0.5 or 1.0 mg ONCE A DAY. Therefore, we know that RPC1063 is likely both effective and safe at that dose. Crestor has a half life of 19 hours and is once a day. Diovan has an even shorter half-life and is once a day.

    There are several reasons why RPC1063 was worth 7B for Celgene and APD334 was not. First, RPC is 2 years ahead in development. Second, RPC successfully completed a large phase II with excellent efficacy and safety data. Third, RPC was shown to have no cardiac effect on an HOURLY basis. Arena only presented DAILY data for APD in a smaller study. If they have hourly data, did they share it with Celgene (if Celgene even looked at APD) and was it good? Why did they not share hourly data in January?

    The best APD can do in a phase II is to be just as good as RPC. Both drugs lowered lymphocyte counts about the same (and about the same as Gilenya) so clinical superiority is unlikely and rare adverse effects are probably going to be similar. RPC was cardiac-safe, so equivalency or inferiority will be shown by APD.

    I think APD will be effective in their phase II. I think there is a good probability it will be cardiac-safe (but not a certainty as hourly data is more important than daily). But since time can never be made up and has tremendous value, they will always be behind. Therefore, after a phase II, the drug will likely have a value closer to 2B if cardiac-safe and negligible if AV block patterns are seen.
    Sep 5, 2015. 02:10 PM | 1 Like Like |Link to Comment
  • Why Anavex Is Leading The Race Against Other Pharma To Help Alzheimer's Patients  [View article]
    I agree with your comments. These results were interesting and I hope large studies show a benefit. I'll keep this stock on my watchlist.

    Quite frankly, not much can be said with data from only 12 patients available. Also, P300 is not a primary outcome endpoint that the FDA would allow for Phase III studies of AD. The ADAS-Cog or MMSE are more standard endpoint. Obviously in Phase II, using a biomarker is fine (in MS phase II studies, MRI is a frequent primary endpoint instead of the more clinically relevent disability progression or ARR).

    P300, IMO, is not a great biomarker. Many things can affect the measurement. Sleep deprivation, medical issues (i.e. hypothyroid), other drugs, mood and even time of day can all affect the latency. Thus, even if a benefit in P300 is seen in a larger study we can't be certain the benefit is cognitive vs mood or previous night's sleep.

    Though care giver's comments in change of behavior is interesting, in a non-controlled study with motivated participants, this can't be looked at as proof
    Aug 29, 2015. 12:14 PM | Likes Like |Link to Comment
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