OMER

Yeah, their early pipeline seems interesting and is my reason for watching but aren't you a bit uncomfortable with such 'too' diverse programs?

OMER

I never dug too deep cause their leading programs didn't seem exciting enough to me - combination of generic drugs in indications I don't know much about.

The observed virologic failure rate that as you've noted in #msg-66069603

Yeah, an amazingly smart and accurate system! was out jogging during the last missiles attack on Tel-Aviv and seen it intercepting the relevant one.
I'm sure RAFAEL are going to have a lot of interest in purchasing the system.

Two words to be proud and thankful about - "Iron Dome"

http://en.wikipedia.org/wiki/Iron_Dome

The system performance was beyond expectations.
There's one placed in our area since this morning, so I no longer have to send you an SMS after every missile :)

A more established rumor on a JV talks between Teva and a South Korea firm:

http://www.globes.co.il/serveen/globes/docview.asp?did=1000798808&fid=1725

Rumors in an Israeli paper on bidders for AMRN

http://www.reuters.com/article/2012/11/15/us-tevapharma-amarin-idUSBRE8AE0P420121115

I recall a discussion we had a while ago on the question if GILD are going to partner or not. I thought they will if they need another drug and oc631 was correct assuming they won't (for example #msg-74594802). One more reason is they think GS-7977+GS-5885 is quite similar to GS-7977+daclatasvir and they get all the rights.

One possible cause for undiagnosed T2D is

Botox in chronic migraines.

A side note on the high percentage of people who don't know they have T2D in the US: I recall reading the percentage in UK is very low (same here), and I wonder if this is the result of different public services or human nature or what?

HCV prevalence vs incidence

We agree on current HCV prevalence estimations in US to be 1.0%–1.5% (it's even a bit higher in EU), and on current estimated population size of 2.7–3.9M, and on about 800K diagnosed cases. We might also agree that CDC estimations, based on HCV antibody prevalence, that current HCV prevalence estimations are low and testing of baby boomers could identify more than 800K additional cases (CDC numbers). So basically we don't agree on acceptance of the test by people.

Sofosbuvir + daclatasvir w/wo riba in GT 1,2,3, 12 weeks data: SVR4 96%, SVR12 100% (from GILEAD's 8-K Form filed on 11/13/12)

HCV prevalence vs incidence (addressing IJ and Clark as well)

CLVS in-licensed the PFE PARP in June 2011 and around that time Astra discontinued their PARP inh (olaparib) in breast cancer in early 2011 and in ovarian cancer later that year. They were well aware of the BRCA mutantions relevance. Perhaps Sanofi's iniparib phase III failure in January 2011 influenced.

GILD

Given the pop on large vol yesterday I guess that data from the 12 weeks without riba are not only good but also leaked from the Late-Breaking Oral Session from Mon.

Sofosbuvir + daclatasvir w/wo riba in GT 1,2,3

I don't see the 12 weeks data yet but if they are similar to the 24 weeks, which is very likely, then we have a proof of concept that 2 DAAs without inf nor riba in one pill a day are good enough for the majority of naive patients. The obvious question for GILD is of course if their own NS5A drug is as potent. If yes, then we won't see more sofosbuvir + daclatasvir combos...

Sofosbuvir + daclatasvir w/wo riba in GT 1,2,3

I can see the abs now. GT1a patients were the majority (73%), riba made no big difference.
See the Itinerary Planner, Late-Breaking Oral Session from Mon:

http://aasld2012.abstractcentral.com/s1agxt/com.scholarone.s1agxt.s1agxt/S1A.html?&CONFIG_ID=2518&USER_ID=1593989&ROLE_ID=16365&ROLE_TYPE_ID=17&PERSON2ROLE_ID=17804403&WORKFLOW_ID=17&CURRENT_PAGE=BROWSE_THE_PROGRAM&ALLOW_EDIT_INSTRUCTIONS_FL=N&SESSION_ADMIN_PERMISSION_FL=N&REVIEWER_ADMIN_PERMISSION_FL=N&DIRECT_LOGIN_FL=Y&HASH_KEY=KuhRF0HUwBW4DFlIFqRjsWu7S6M&STUB_ROLE_ID=0&TIME=1352813372302&SOURCE_URL=http://aasld2012.abstractcentral.com

ABSTRACT BODY: Background: Oral combinations of direct-acting antivirals may provide new options for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (DCV) plus sofosbuvir (GS-7977, SOF) with and without ribavirin (RBV) in previously untreated patients with chronic HCV genotype (GT) 1, 2, or 3.

Methods: This parallel-group, open-label study randomized 44 GT1 and 44 GT2 or 3 HCV-infected, non-cirrhotic patients 1:1:1 to SOF for 7 days, then DCV+SOF for 23 weeks; DCV+SOF for 24 weeks; or DCV+SOF+RBV for 24 weeks. By a protocol amendment, an additional 82 GT1 patients were randomized 1:1 to DCV+SOF with or without RBV for 12 weeks. DCV and SOF were dosed orally at 60 mg QD and 400 mg QD (126 GT1; 44 GT2/3), respectively. RBV was dosed orally BID at 1000-1200 mg/d in GT1 and 800 mg/d in GT2/3 patients. The primary end point was HCV RNA <25 IU/mL (LLOQ) at 12 weeks post-treatment (PT; SVR12). Results of 24-week arms are described; SVR4 for 12-week arms and complete SVR24 for 24-week arms will be presented.

Results: The majority of GT1 patients (24-wk arms) were GT1a (73%); GT2/3 patients were 59% GT2, 41% GT3. Mean HCV RNA was =6.5 log10 IU/mL in all groups. 100% (44/44) of GT1 and 91% (40/44) of GT2/3 patients achieved SVR12. Of those not achieving SVR12 , 1 (GT3) relapsed at PT week 4 (a pre-existing NS5A-A30K polymorphism was detected); 2 were lost to follow-up (1 later returned with undetectable HCV RNA at PT Week 24); and 1 had PEG/RBV added per protocol. For those reaching PT Week 24, 39/40 GT1 and 41/43 GT2/3 patients achieved SVR24. One patient (GT1a, IL28B CT; SOF lead-in + DCV + no RBV) with SVR12 relapsed at PT week 24 (HCV RNA 670772 IU/mL); interestingly, HCV RNA was 98 IU/mL on repeat testing. There was no difference in response by GT1 subtype (1a/1b), IL28B genotype, or inclusion of ribavirin. The most common adverse events (>20%) were fatigue, headache, and nausea. The most common grade 3-4 laboratory abnormality was anemia, which occurred only in patients receiving RBV.

Conclusion: 24 weeks of the all-oral, once-daily combination of DCV plus SOF achieved high rates of SVR12 in previously untreated patients with HCV genotype 1, 2, or 3. IL28B genotype, genotype 1 subtype, and the use of ribavirin did not influence response. SVR4 following 12-week treatment will be presented.

ABT's data are indeed as good as can be but it is also clear that ribavirin is there to stay and if GILD can come up with pretty close SVR rates and safety profile with just 2 DAAs which are taken in one pill a day, it's an important advantage imo.

Sorry, i was talking about the data presented at EASL earlier this year. Haven't seen the poster from AASLD yet.

GS-7977 + daclatasvir 100% SVR

I think that 32 out of the 44 GT1 patients were GT1a and 12 GT1b

Think it was 1000 to 1200mg (weight-based) daily, but quite sure it wasn't 800mg.

GILD

The idea I identify with from your link:

A comment by Professor Leigh Turner of the University of Minnesota Center for Bioethics about ethical issues related to that PSTI case:

The patient died in Oct. but accusations in the press are from today! here are two more:

http://www.fiercebiotech.com/story/after-cashing-life-saving-boast-biotech-stayed-mum-patient-death/2012-11-08

http://www.sfgate.com/business/bloomberg/article/Girl-Dies-as-Pluristem-Sells-on-Gains-With-4020258.php

PSTI down 20%

The 7 years old girl died and accusations are being made:

http://washpost.bloomberg.com/Story?docId=1376-MCA9A26S972N01-1ETTE08HA59AJJJQQ9UL9FOSMN

I think it is already clear that PCSK9 inhibition is very effective in lowering LDL-C and safety looks ok so far but too early to know. As for use, beyond narrow indications like FH this class will need to show benefit in decreasing CV and stroke risk and death in huge outcomes studies like you've mentioned, plus the drawback of being injectables.