Biomarin – testing the boundaries of evidence-based medicine

As an outside observer to the rare disease community, I find the recent acquisition of Prosensa (RNA) by Biomarin (BMRN) puzzling. To me, Prosensa’s drisapersen was just another case where promising phase II results were not corroborated in phase III. This happens frequently with oncology drugs (metmab, iniparib, tivantinib, palifosfamide etc.) and typically leads to termination of the program. Judging by Biomarin’s optimism, drisapersen’s fate may be different, which raises questions regarding approval of drugs despite negative P3 outcome. As background, Prosensa’s lead drug, drisapersen, is being developed for the treatment of DMD (Duchenne muscular dystrophy), a devastating and fatal muscle-wasting disease that affects young boys. The drug addresses 13% of DMD cases and works by a new mechanism (exon skipping). Sarepta (SRPT) is developing a competing drug (eteplirsen) that works by the same mechanism.

Promising phase 2 data…

Prosensa went public based on positive results from a 53-patient randomized phase II (DEMAND II). The trial compared 2 regimens of drisapersen (continuous and intermittent) to placebo, with 6-minute walk distance (6MWD) as the primary endpoint. 6MWD measures the distance a patient is able to walk over a period of 6 minutes and is regarded as a reliable way to assess disease progression. In DMD, the minimally clinical improvement is considered to be 30 meters.

The continuous drisapersen arm demonstrated a ~35 meters after 24 weeks, which was maintained at 48 weeks. The difference at 24 weeks was statistically significant whereas the benefit after 48 weeks was almost statistically significant (p= 0.051).

DEMAND II… not corroborated in phase III

Based on these promising results, Prosensa advanced drisapersen to phase III, which failed to show any benefit after 24 or 48 weeks. The absolute difference at 48 weeks was 10.3 meters in favor of drisapersen, which was not statistically significant (p= 0.42) and is not considered clinically meaningful.DEMAND III In parallel, Prosensa and its partner at the time, GSK (GSK), released results from another small phase II (51 patients) which evaluated two doses of drisapersen vs. placebo. The higher dose led to a 27-meter benefit over placebo after 24 weeks but the difference was not statistically significant (although it was close: p=0.069).

Mixed signals

This created a situation where the drug had positive readouts from two different randomized phase II trials but a completely negative readout from a large phase III study.

In order to reconcile this discrepancy, Prosensa and Biomarin argue that the phase II trials, coupled with other long term open label studies, represent the true activity of drisapersen. The phase III failure was blamed on trial design issues such as patient heterogeneity, a high proportion of more advanced DMD patients and insufficient follow-up.

A quick comment on data presentation

In an attempt to convince investors and regulators that the phase III had a different patient population, Prosensa created a slide (see below) that compared baseline characteristics across the different studies. To me, the slide is misleading because the graphical presentation makes the differences look more dramatic than what they are (X and Y axis do not cross at 0). For example, the “time since diagnosis” graph gives a sense of a 3-4 fold difference while in fact the actual difference was only 29%. When companies use these tricks it should be viewed as a major red flag.

Baseline - ProsensaIn Biomarin’s defense, they changed these graphs, and in their presentations the differences look much more subtle.

Baseline - BiomarinReality check

Going back to Biomarin’s claims regarding trial design issues as the reason for the phase III failure, the arguments provided to date focus on disease severity and insufficient follow up.

Disease severity – Subset analysis of the phase III data based on age and disease severity did not reveal much in terms efficacy. Subset analyses are unreliable by nature and in this case, they didn’t even lead to a significant benefit. The best subset analyses improved absolute difference between the drisapersen arm and placebo to 21-25 meters but this did not come close to statistical significance, with a sample of 47 and 79 patients, respectively. This is notable given the fact that the two positive phase II studies were able to show a statistically significant (or on the verge of stat. significance) with 34-36 patients.

DEMAND III - subset analysisPTC Therapeutics (PTCT), which is developing ataluren for another subset of DMD patients, also used subset analysis from its randomized phase II and reached the opposite conclusion. PTC decided to recruit older patients with more advanced stage DMD for their ongoing phase III study based on the idea that it will be hard to show a clinical benefit in patients with early-stage disease because they experience very limited deterioration initially (up to 48 weeks). This can also explain the spectacular results with drisapersen in small single arm studies: Some patients do very well, regardless of treatment (see right graph below).

PTCLonger follow up – The need for long- term follow up in order to see an effect contradicts the signals observed in the phase II studies, where a clear effect was seen even after 24 weeks. Therefore, this argument discredits the efficacy signals from the phase II trials.

At JPM, Biomarin’s CEO presented updated results from the phase III extension study, in which patients from the placebo arm crossed over to receive drisapersen (patients originally assigned to drisapersen vs. patients who crossed over from the placebo arm). After 2 years there was a 49.2 meter difference between the two arms. No p value was provided so one can assume the difference wasn’t statistically significant.

DEMAND III - long term FURegardless, this analysis is very hard to interpret as the drug is compared to itself from the 48 week time point and included a small number of patients. As not all patients continued to receive the drug, the two arms were probably not carefully balanced. Therefore, the difference between the two arms could be a result of natural variability between the groups. In addition, landmark analyses are unreliable if they are not defined prospectively before results are available. Without this, one can go over the graphs looking for a single time point in which the difference is maximal.

Summary

Drisapersen generated intriguing signals that may merit further evaluation but in my opinion, the totality of data fails to prove drisapersen provides any benefit in DMD. If Biomarin truly believes the drug is effective, the right thing to do is a new pivotal trial applying the new selection criteria and endpoints. Instead, Biomarin intends to file for approval with a predominantly negative package which is full of inconsistencies and inherent discrepancies.

The phase III failure and the lack of any positive subset analysis are an order of magnitude more reliable than any positive indication from smaller studies (either placebo controlled or single arm). Despite this, Biomarin believes drisapersen could receive accelerated approval, which is quite unusual for a drug that proved ineffective in phase III. There is no doubt that new DMD treatments are urgently needed but one has to wonder whether this can be an excuse for approving drugs based on unmet need while ignoring basic tenets of  evidence-based medicine.

Portfolio updates

We are selling one of three positions in Foundation Medicine (FMI) following the 100% jump earlier this month (in order to limit exposure to 10% of total holdings).

Portfolio holdings – January 25TH, 2015

Biotech portfolio - 25-1-15biotech etfs - 25-1-15

72 thoughts on “Biomarin – testing the boundaries of evidence-based medicine

  1. Ohad, I have to disagree here. One thing you didn’t mention was Drisapersen ph3 trial was initiated with wider inclusion criteria well BEFORE two randomized ph2 trials. Thus this is an unusual case where tightened inclusion criteria from two ph2 trials was closer to current understanding of ambulant DMD with 6MWT as endpoint.

  2. Ohad
    Congrats on your recent successes!!
    Do you think that the requirement that ARRY find a Global Development Partner for both drugs will mean that they don’t do a financing?

  3. Ohad
    your articles have very high educational value and we are learning from you vast knowledge in the biotech field.
    However I am confused from this article – what is actually your massage?
    Is there any take away which I missed to recognize?

    This week is the IPO of Spark. What is your opinion about this company? Their IPO valuation ($378M) does not look high for an advanced Ph 3 company. Their roadshow presentation is very impressive.
    –thanks–

  4. JQ – It doesn’t change the fact that large multi-center studies are more reliable than small trials, where statistical flukes often happen. Prosensa had DEMAND II data before unblinding the P3 study. Besides, even when they did the relevant subset analyses (which are unreliable by nature) they couldn’t see a real benefit.

    Regarding inclusion of BMD patients, my understanding is that the vast majority of patients in their data were DMD (and this is how they present the results on a regular basis). See below their natural history study where they write:

    “Although Becker muscular dystrophy (BMD) patients could theoretically have been included in our study, the study population was primarily DMD patients, given the inclusion criteria of more severe disease phenotype”

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824082/

    btw, check out figure 6c, which clearly shows an improvement in patients < 7 years... Declan (ARRY) - Thanks. I still think they need to do a financing to support US development and to strengthen negotiation leverage. After last week's jump, things look much better. Ohad

  5. Ohad, Figure 6 placebo patients <7 years old result came from N=6 patients. As of PTCT didn't think they included many BMD patients in their ph2/3 trial, just compare 6MWT from placebo patients in that trial with Drisapersen placebo patients from all three randomized trials, the differences were striking. PTCT used to say DMD/BMD in all of their PRs and presentations regarding the ph2/3 trial, only in the last two years it started to omit BMD patients. I have followed PTCT for a long time, years before it became a public company.

  6. Hi Ohad,
    Thanks for an educating and insightful article. If you’ve looked a little at companies developing DMD drugs (albeit as an outside observer), I would love to know if you have any opinion about Sarepta’s (SRPT) results. They have been publishing periodic results from the continuation of their Phase II trial on a very small group (10) patients. On this group the results look very promising, especially since they’ve continued to show good results over more than 3 years. Even more promising IMHO is the fact that their drug doesn’t seem to cause any serious adverse effects. On the other hand, they have not run a serious phase III multi-center trial. The FDA is giving them the thumbs down at this stage due to disagreement over the reliability of the 6MWT, but I’m interested whether you think their current results may be a good basis for approval assuming that the 6MWT is considered reliable.
    Thanks

  7. Steve (EXEL) – At the moment I don’t have any plans to get back in, perhaps later in the Q going into the RCC data (high risk but single arm trial was impressive + we know multi-target kinase inhibitors work there).

    Aviv (SRPT) – What bothers me the most in SRPT is the fact they haven’t conducted additional studies since the initial positive readout. In contrast to drisapersen, there is no robust P3 which proves eteplirsen doesn’t work. In general, I don’t think that a n=12 study can justify approval in most indications.

    Ohad

  8. Hi Ohad, not sure if you saw andre’s posting, as I am also curious re your opinion on the IPO of Spark this week. Thank you!

  9. Kevin – Not an expert in ophthalmology but I like Spark and valuation doesn’t seem to be exaggerated.

    Sorry, Andre, for missing your question.

    Ohad

  10. Good morning Ohad,

    I think it was at the end of last year, when you told the community you sold some of your genmab stocks. Until now, they nearly doubled. Do you think genmab isn’t flying under the radar anymore or do you have another explanation for this development? Do you think genmab is overvalued right now?

    Thank you as always!

    Martin

  11. Hello Ohad,

    finally ARRY has a market cap of approx. USD 1 billion. What do you think of the potential from here? what can be a realistic market cap if MEK162 and selumetinib suceed?

    thanks
    Christian

  12. Ohad
    did you ever look at Silence Therapeutics (SLN.L) and do you have
    an opinion on it ? Thanks

  13. Hey Ohad
    another immuno-oncology play – HTBX – with very low market cap announced some preliminary trial results yesterday (not at a conference, but press release)
    Would love to hear your opinion!
    Dan

  14. Drisapersen also has significant renal toxicity issues, so that’s another argument against approval, especially if the benefit is uncertain. About the P2 trials, there is some evidence that the studies weren’t truly patient-blinded, since the injection can cause strong pain locally, so the patients knew whether they were getting drug or placebo (about an 80% reported rate of local adverse reaction reported). When you’re talking about a walking test, motivation can be a strong factor modulating the results. I don’t know if this was corrected somehow in the phase 3 trial.

  15. Martin (GEN) – Yes I did sell 50% of my holdings and the stock continued to soar…
    I don’t think they are flying under the radar anymore and expectations are very high going into the pivotal P2 data. With a market cap approaching $4B, the current price has good data baked in, so it certainly isn’t cheap.

    Christian (ARRY) – $1B sounds fair for a company with 2 P3 assets and the optionality they represent. To me, the big question is Array’s partnered pipeline (selumetinib, Genentech’s Akt and ERK programs, LOXO101 etc.).

    Rodolfo – Sorry, not very familiar with them.

    Dan (HTBX) – The data they describe is intriguing at first glance but for me it’s hard to draw any definitive conclusions as the trial included treatment with BCG which is an immune-stimulating agent and immunologic responses do not necessarily translate to clinical responses.

    Johnnyboy – Thanks for raising these important points, don’t know how injection site reactions were dealt with in the randomized trials. We know there was limited patient drop-off, so I assume this was not a major issue.

    Ohad

  16. Hi Ohad,

    Regarding ARRY and valuation, given that PD1’s are very effecting against melanoma and that there are two other MEK/BRAF combinations well ahead of ARRY, isn’t a 1B+ valuation a bit optimistic? Also if ARRY HAS to partner then the assumption is that it only owns a portion of the combination isn’t it? Any thoughts on what type of partner ARRY may be able to land?

  17. hi ohad. do you have any opinion on sangamo biosciences (SGMO)? there technology seems interesting for gene regulation and modification. many thanks for your insight!

  18. Hi Ohad!

    what do you think of the XNCR Asthma-data? Looks very good? (Xolair a blockbuster although possibly considerably less effective)

    thanks
    Christian

  19. Ohad,
    How much is the risk factor to get into MRNS now. Is this a most risky stock in your portfolio. Whose results will be out frist MRNS or SAGE ? What is the next catalyst for 2 companies. Thanks

  20. Hi Ohad,

    Any updated opinions on MGNX or EPZM here? I know you’ve considered them too expensive in the past. MGNX in particular has a very broad partnered pipeline and is working in the buzzy immuno-onc space, but pretty early stage.

    Thanks,
    Sherk

  21. Rick (ARRY) – Agree, PD-1 antibodies are very effective but I still expect MEK/RAF regimens to play an important role in PD-1 failures and in combination with PD-1 antibodies. The $1B valuation looks fair (but not cheap) to me based on a modest market share in BRAF+ melanoma, a good market share in NRAS melanoma (where data is weaker) and a host of other indications like colon, lung and ovarian cancer with RAF/RAS mutations. And then you have multiple partnered programs could become meaningful this and next year.
    Yes, if ARRY partners it will only have a stake in the franchise but this is already baked in the price either as a rich royalty deal or as a reason for someone like Merck or Pfizer to buy the entire company.

    Dan S.(SGMO) -Don’t know the field well but my impression is that the zinc finger tech is inferior to new technologies such as CRISPR.

    Christian (XNCR) – Looks good, total IgE reduction appear dramatic and may suggest their mAb is superior to Xolair but data are still limited. Side effects at the 3 mg/kg arm is another thing to track (they plan on using lower doses but still). Need to do more homework on that one….

    Chris (AAVL) – I wish I had a good answer for you. Bottom line, I don’t own them even after the correction but if their p2 data next Q replicates P1 data then it’s a huge ($5B+ product).

    ruhulla (MRNS)- I don’t think it is the riskiest stock on my portfolio. CNAT and ARQL are much riskier imo. In terms of news flow, the main readouts will be the two orphan indications PCHD19 and Fragile X) in 1H and mid-2015, respectively and then results in refractory epilepsy in 2H15. For SAGE, the majority of focus will be on SRSE updates and regulatory clarity.

    sherk (MGNX/EPZM) – If I had to pick one, I would go for MGNX for the reasons you mention. I like their CD123 bsAb for AML, should have data this year. EPZM is still too expensive imo as data for both programs, DOT1L and EZH2, is not that impressive imo.

    Ohad
    .

  22. Hi Ohad,

    Do you have any thoughts on a couple of diagnostic firms, Invitae and Adaptive? Invitae is set to IPO and Adaptive probably isn’t far behind given the current IPO market and FMI’s success. The price at IPO will likely be too high, but are these firms worth keeping a watch on? Or generally, besides Foundation, are there any other diagnostic companies you think are exciting?

    Thanks,
    Sherk

  23. Steve (EXEL) – Don’t know the reason for the recent strength in the stock. I am considering buying a small position before the Q2 data in RCC.

    sherk – Sorry, I am not very familiar with the Dx space, FMI is an exception because I view it as an enabler of drug development.

    Ohad

  24. Hello Ohad
    good news for espr, would you consider adding or the risks are as before?
    Thanks
    Alex

  25. sounds not bad – taken from ARRY Q press release

    ARRY-797 (ARRY-371797)
    (…) As of January 2014, the trial has patient experience up to 36 weeks and ARRY-797 has been well-tolerated. Preliminary data at early time points are encouraging for multiple endpoints across patients, but further data is needed to fully assess the magnitude, consistency and durability of effects.

  26. Ohad
    Genmab posted Daratumumab data in Double Refractory Multiple Myeloma
    ORR about 29% and median duration 7.4 months is a bit better than what you expected – better that 25% and at least 6 months. You said that this should be sufficient to apply for accelerated approval already in 2015.
    So, why the stock is 14% down? Were the market expectations different?

  27. EXEL
    Reason for good performance could be (not sure) that Roche disclosed 2 new Cobi trials on their recent CC. One is a PII in TNBC and one is a PI combination study (HER3/EGFR DAF) in KRAS pos tumors. It is in their presentation on side 79…

  28. XNCR – Ohad, curious on recent XNCR Phase 1 asthma data. Stock seems fairly reasonable risk-reward here if one truly believes this drug has the chance to be better than Xolair. But, does it? The drug reduces IgE down to undetectable levels in most patients for at least a week. What does this mean? I don’t think they will be dosing the drug weekly so what does this mean when IgE levels go back up in the interim between doses? Will there still be enough of an impact to have meaningful effect on asthma?

  29. Alex (ESPR) – Indeed good news, have to say I was surprised by the positive reaction as I had considered this to be already priced in. Yes I am considering to add more as a buyout make take place already this year.

    Christian (ARRY) – The ARRY797 story is very interesting, hard to interpret without seeing the complete data set.

    andre (GEN) – This looks sufficient for accelerated approval. Activity isn’t spectacular as I had originally hoped but CD38 antibodies will likely become an important part of myeloma combination regimens. Stock reaction simply implies the market expected something better.

    Richard (ArgenX) – Cool science and platforms, the problem is with finding the right targets and applications.

    ike (EXEL) – Perhaps. More trials is an obvious positive, the most important study is with PD-L1 in KRAS+ NSCLC.

    mcbio (XNCR) – The question I am struggling with is whether the dramatic reductions in total IgE translate to better clinical outcome (makes sense). Also, it’s a shame they didn’t do a head-to-head study vs. Xolair to give a better sense on differentiation.

    Ohad

  30. I was trying to understanf the sec filing that ARRY did today:

    Text from it:
    “We have received a total of $669.9 million in research funding and in up-front and milestone payments from partners from inception through December 31, 2014, including $174 million in initial payments from strategic agreements with Amgen, Celgene, Genentech, Novartis and Oncothyreon that we entered into over the last five years. Our existing partnered programs entitle Array to receive a total of over $2 billion in additional milestone payments if we or our partners achieve the drug discovery, development and commercialization objectives detailed in those agreements. We also have the potential to earn royalties on any resulting product sales or share in the proceeds from licensing or commercialization from 13 partnered programs.”

    Does this mean, ARRY is projecting its company valuation to be 2 billion.

  31. Alex (FMI) – I wouldn’t pay attention.

    Ruhulla (ARRY) – They simply provide an overview of their partnerships, I wouldn’t infer anything about potential market cap.

    Ohad

  32. Ohad
    GSK is selling all GEN shares, 4.47M. They will not have any ownership in the company. Any concern about your Genmab position?

  33. hey Ohad
    ESPR? Saw your post about adding to the position. What do you think would be the timeframe and price point for this? Close to $1billion market cap already. Hard to guess, but looking at FMI, maybe the acquisition might happen sooner thanl later.
    Thanks for the perspective!
    Dan

  34. Hello Ohad,
    Incyte is the largest single stock in ypur portfolio with the largest gains. Do yyou still believe its a buy or is just a hold for now? ,Thanks.

  35. andre (GEN) – Doesn’t change my view on the company. Probably has to do with the GSK/NVS asset swap.

    Dan (ESPR) – ESPR (and also AERI) has a decent shot of getting bought as it is a rare opportunity for any company with a metabolic franchise (only proven oral pill for LDL with proven efficacy) and on the other hand, pursuing such a program may be too ambitious for a small company like ESPR. Very hard to predict timing of these things, my guess is mid-year but just like FMI, impossible to predict.

    gerwei (AERI) – I like them, same reasons described above for ESPR.

    sam (INCY) – On the one hand I view INCY is a remarkable company and a core long term holding. On the other, I can’t argue it’s cheap even when rosy predictions in PV are taken into account.

    denny (FPRX) – Too expensive imo.

    Ohad

  36. Hi Ohad, what you think MEIP? “Pracinostat” showed good data on AML and MDS, only 128M. Thanks.

    Jinyu

  37. Hi Ohad,

    What you think of MEIP? Pracinostat, a HDAC inhibitor showed Impressive data so far on AML and MPS in combination with CELG Azacitidine. Low evaluation @86M. Thanks! Jinyu

  38. Ji (STML) – I view it as a high risk bet and intend to keep a small position. I like the strong preliminary efficacy in a niche indication (BPDCN) but am still concerned about immunogenicity and competition from MGNX.

    Jinyu (MEIP) – I am still struggling with this one. I agree valuation is low but the recent AML update was somewhat disappointing. For the time being I am out but I have a month to change my mind….

    Ohad

  39. Hello Ohad! There was quite a movement in Arqule today {2/11/2015}…….Do you have any comments? I am also interested in your insight in to the recent news on Curis!? Thank you in advance!

  40. Bouschka – Re: ARQL, I am not aware of any particular development. Re: CRIS, I liked the IRAK program they got from Aurigene, the small molecule PD-1 inhibitor is less attractive and quite risky imo.

    Ohad

  41. Hi Ohad,
    Do you think AGIO is worth its market cap? It looks to be a great short candidate. Aside from some individual stocks, do you see much upside for the biotech sector for 2015. Maybe I’m wrong, but I sold all my FMI and half my ARRY today. I did buy a decent chunk in ARQL (probably one that is fairly valued).

  42. Hi Ohad

    I read your comments on ESPR and AERI. As someone who doesn’t hold stocks in any of those two, do you think it’s still a good idea to jump into those two?

  43. hi Ohad,

    I have the feeling that some strange things are going on at ARRY, e.g. just from today’s 8K:

    http://investor.arraybiopharma.com/phoenix.zhtml?c=123810&p=irol-SECText&TEXT=aHR0cDovL2FwaS50ZW5rd2l6YXJkLmNvbS9maWxpbmcueG1sP2lwYWdlPTEwMDczMDU2JkRTRVE9MCZTRVE9MCZTUURFU0M9U0VDVElPTl9FTlRJUkUmc3Vic2lkPTU3

    are they clearing the ship for a takover??

    everything is contingent on the Novartis-transaction. maybe they already have a buyer who will swallow them once the ok for the Novartis/GSK-deal is there?

  44. ok maybe I am interpreting too much into it….

    still I think a buyout is likely with >20 % within the coming few months

  45. Manish – Re: AGIO, I think the stock is overvalued but I also thought so when it was at $50…. In general I agree that biotech as a sector is somewhat overvalued, ARQL clearly isn’t but it’s a very high risk play so I plan to keep my exposure low.

    Ji (ESPR/AERI) – I believe that at least one of them will be acquired during 2015 so I intend to hold and add on weakness. From a philosophical standpoint, holding a stock is the same as buying it.

    Christian (ARRY)- I don’t expect a buyout wit the present valuation, a licensing agreement looks more likely imo.

    Ohad

  46. Dear Ohad:
    Your analysis of the DMD drugs from Biomarin/Prosensa and Sarepta was excellent. I looked into these drugs some time ago when the first results were coming out. Sarepta showed data from biopsied muscle to show how much dystrophin was being made in boys who were taking the drug. They had two kinds of measures. First, they used microscopy and antibodies against dystrophin to measure the percentage of muscle cells that contained dystrophin. Without drug, that number was zero, and with drug, that number was high (I can’t remember the number, but let’s say 75%). So, a lot of the muscle cells were indeed making at least a little bit of dystrophin. Second, they showed one Western blot in which the amount of dystrophin in the muscle cells was assayed, compared to normal muscle. That Western blot showed that the absolute amount of dystrophin was really tiny. I did a rough estimate at the time, which again I cannot exactly remember, but I think it was around 1% of normal, or even less. So, the Sarepta drug was inducing about 1% of normal levels of dystrophin in about 75% of cells. There are several published studies looking at mice producing very low levels of dystrophin. These tend to say that (a) there is some slight benefit to very low levels of dystrophin, but (b) it is a very slight benefit, sort of proportional to the amount expressed. Putting all this together, I guess that both the Prosensa/Biomarin and the Sarepta drugs will produce tiny benefits, but unfortunately those benefits will be really pretty small.

    Since there is published data (from mice) on the effects of small amounts of dystrophin, it seems the two companies could clarify things substantially by telling us how much dystrophin is being made (i.e., not the number of cells that are positive, but the amount of dystrophin).

  47. Hi Ohad

    Have you ever come across Cytori Therapeutics (CYTX). They are working in the field of adipose derived stem cells. Last management was crap and the balance sheet still looks bad – though the technology seems to work and very promising.

    Thanks for your thoughts!

  48. Dan S. (AERI) – News about potential disease modifying properties of Rhopressa are positive for the overall prospects of the drug (needs to be validated in humans, of course), but the upcoming p3 data are an order of magnitude more important. The preclinical program in AMD has good data but I am still cautious as small molecules for AMD are inferior by definition due to duration of exposure.

    Bruce (BMRN) – Thanks. Quantifying dystrophin is tricky by definition as the methods currently used may be biased due to fluctuation or subjective interpretation. I agree that perhaps the disappointing clinical results stem from subtle potency, which, if amplified could be clinically meaningful.

    Kevin (CYTX) – Haven’t looked at them for a long time.

    Alex (TKAI) – Don’t know them too well, but their data even in AR-V7 patients were not a home run imo.

    Alex (OGXI) – I still think their drugs don’t work.

    Ohad

  49. OGXI – I never shorted a stock yet but what do you think about shorting it?

    TKAI – you meen as opposed to –
    Analyst Dr. Brian Klein of Stifel initiated coverage at “buy” and a price target of $20. He said galeterone has shown compelling early evidence of efficacy in a genetically defined and underserved population in Phase 2 testing. “We believe similar results in Phase 3 would be a home run.” October 13, 2014 ☺

  50. Hi Ohad,

    What do you think the valution of these three CAR-T players: JUNO, KITE and BLCM? Thanks!
    bj

  51. Hello again Ohad ! In researching Aeri, I came across a company called Inotek.I would appreciate any comments you may have.

  52. Hello Ohad,

    Valeant Pharmaceuticals bought Dendreon Corp due to its prostate cancer vaccine Provenge for $ 400 Mio. Medigene has a more effective new generation dendritic cell vaccine in development which can be produced very cost effective – in contrast to Provenge. Medigene has a market cap of EUR 55 Mio. Wouldn’t this be an interesting – of course speculative – play? Thanks.

    Toby

  53. Hello Ohad,
    Do you have any opinions on Xenon Pharmaceuticals Inc. (XENE), specifically it’s platform.
    Also, what do you think of the recent increased institutional investment activity in Advaxis, Inc. (ADXS).
    Thanks,
    Frank

  54. Alex – I don’t do shorts. Regrading TKAI, Brian is a very smart guy and probably knows them much better. The totality of their data was not compelling imo, will check again when I have an opportunity to do so.

    bj – Sorry can’t discuss te CAR space.

    Bouschka (AERI) – Inotek just did an IPO, they have positive P2 data but their story is not as compelling a AERI imo.

    Toby – DNDN’s Provenge is the only dendritic cell vaccine that led to a survival benefit in P3. In general, I am somewhat cautious about cancer vaccines in development although the sentiment has improved in the past couple of years.

    Frank – Sorry, I am not very familiar with both.

    Ohad

  55. Ohad,
    I read some of your blogs, you covers a wide variety of life science and biotech topics. you did good job in presenting yourself as an expert in almost all the topics you blogs – certainly a very useful skill. You seemed holding very strong opinion in this article – not sure why. An unbiased analysis of the topic would be more valuable than throw out an opinion at readers. I think most readers of your blogs are well educated, they would rather form their own opinions if you could just provide unbiased evidence and analysis. I like the evidences JQ brought up.
    Every drug has a long list of side effects. Look at tylenol – everyone use it. do you think people will stop using tylenol after reading this article? http://articles.mercola.com/sites/articles/archive/2013/12/03/acetaminophen-alcohol.aspx.
    You probably know that people have higher tolerance in side effects when dealing with difficult-to-treat life threatening diseases (e.g. cancer, DVD…) versus none life threatening diseases.

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