[Ip-health] Eminent domain

George Carter fiar at verizon.net
Fri Nov 16 06:18:31 PST 2012

On Nov 15, 2012, at 10:17 AM, George Carter wrote:

> If ever there was a case to invoke eminent domain, this is it.
> Promising HCV Combo May Not See Light of Day

This isn't just promising - at week 12 AFTER treatment stopped (sustained viral response), a FULL 100% of genotype 1a and 1b patients remained undetectable.

And 86% to 100% of genotype 2 and 3--WITHOUT viciously toxic, horribly costly alpha interferon. (And in fact, probably better without anemia-inducing ribavirin...) And only a total time on drugs of 24 weeks.

Yet, CEO John C. Martin of Gilead says "no further study permitted"!! 
George M. Carter

CONTROL ID: 1540979

Co-Author Disclosure Status
PRESENTATION TYPE: Late Breaking Oral or Poster
CURRENT DESCRIPTORS: S05. HCV: Clinical Trials and Therapeutic Developments
TITLE: High Rate of Sustained Virologic Response with the All-Oral Combination of Daclatasvir (NS5A Inhibitor) Plus Sofosbuvir (Nucleotide NS5B Inhibitor), With or Without Ribavirin, in Treatment-Naïve Patients Chronically Infected With HCV Genotype 1, 2, or 3
AUTHORS (FIRST NAME, LAST NAME): Mark S. Sulkowski1, David F. Gardiner2, Maribel Rodriguez-Torres3, K. Rajender Reddy4, Tarek Hassanein5, Ira M. Jacobson6, Eric Lawitz7, Anna S. Lok8, Federico Hinestrosa9, Paul J. Thuluvath10, Howard Schwartz11, David R. Nelson12, Timothy Eley2, Megan Wind-Rotolo13, Shu-Pang Huang13, Min Gao14, Fiona McPhee14, Diane Sherman2, Robert Hindes15, William T. Symonds15, Claudio Pasquinelli2, Dennis M. Grasela2
Institutional Author(s): AI444040 Study Group
INSTITUTIONS (ALL): 1. Johns Hopkins University, Baltimore, MD, United States. 
2. Bristol-Myers Squibb, Hopewell, NJ, United States. 
3. Fundación de Investigación, San Juan, Puerto Rico. 
4. University of Pennsylvania, Philadelphia, PA, United States. 
5. Southern California Liver Center, Coronado, CA, United States. 
6. Weill Cornell Medical College, New York, NY, United States. 
7. Alamo Medical Research, San Antonio, TX, United States. 
8. University of Michigan, Ann Arbor, MI, United States. 
9. Orlando Immunology Center, Orlando, FL, United States. 
10. Mercy Medical Center, Baltimore, MD, United States. 
11. Miami Research Associates, South Miami, FL, United States. 
12. University of Florida, Gainesville, FL, United States. 
13. Bristol-Myers Squibb, Princeton, NJ, United States. 
14. Bristol-Myers Squibb, Wallingford, CT, United States. 
15. Gilead Sciences, Foster City, CA, United States. 
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.

HCV RNA < LLOQ, n (%)	SOF x 7 days, then DCV + SOF 
x 23 weeks	DCV + SOF 
x 24 weeks	DCV + SOF + RBV 
x 24 weeks
(n = 15)	(GT2/3) 
(n = 16)	(GT1a/1b)
(n = 14)	(GT2/3)
(n = 14) 	(GT1a/1b)
(n = 15)	(GT2/3)
(n = 14) 
Week 4	15 (100)	16 (100)	14 (100)	14 (100)	15 (100)	14 (100)
EOTa	15 (100)	15 (94)b	14 (100)	14 (100)	15 (100)	14 (100)
SVR4	15 (100)	14 (88)c	14 (100)	14 (100)	15 (100)	12 (86)d
SVR12	15 (100)	14 (88)	14 (100)	14 (100)	15 (100)	12 (86)
aEnd-of-treatment (EOT) includes patients who discontinued early, with last visit considered EOT. b1 patient with addition of pegIFN/RBV (rescue); c1 relapse; d2 lost to follow-up after week 18 and 24, respectively—both had undetectable HCV RNA at the last visit

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