Bristol-Myers Tops Estimates on Cancer, Hepatitis C Sales

Bristol-Myers Squibb Co., a drugmaker increasingly focused on developing new cancer treatments, beat third-quarter profit estimates on better-than-expected revenue from its oncology drug Opdivo and the start of U.S. sales for its hepatitis C drug.

Third-quarter earnings, excluding one-time items, were 39 cents a share, beating the 35-cent average of analysts’ estimates compiled by Bloomberg. Sales rose 3.7 percent from a year earlier to $4.07 billion. Analysts had estimated $3.86 billion on average.

The New York-based company also raised its full-year sales forecast to a range of $16 billion to $16.4 billion, from a prior projection of $15.5 billion to $15.9 billion, and increased its full-year adjusted earnings forecast to $1.85 to $1.90 a share, from a previous estimate of $1.70 to $1.80 a share. It’s the third time Bristol-Myers has raised its earnings projections this year.

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U.S. FDA Grants Priority Review For Daklinza (daclatasvir) sNDA

Three applications are under review for Daklinzain combination with sofosbuvir with or without ribavirin to treat chronic hepatitis C patients with decompensated cirrhosis, post-liver transplant recurrence of HCV, and coinfection with HIV-1

Bristol-Myers Squibb’s U.S. registration focus for Daklinza is based on addressing the treatment needs of challenging HCV patient populations

October 06, 2015 07:00 AM Eastern Daylight Time

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that the U.S. Food and Drug Administration (FDA) has accepted for filing and review three supplemental New Drug Applications (sNDAs) for Daklinza (daclatasvir), an NS5A replication complex inhibitor, for use with sofosbuvir with or without ribavirin. The applications are for the treatment of patients with chronic hepatitis C (HCV) coinfected with human immunodeficiency virus (HIV-1), patients with advanced cirrhosis (including decompensated cirrhosis), and for patients with post-liver transplant recurrence of HCV.

In the U.S., the FDA grants priority review status when an investigational medicine, if approved, would offer a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. The FDA will review the three Daklinza sNDAs within a six-month timeframe.

“Hepatitis C is not a one-size-fits-all, monolithic disease. Our focus for the Daklinza-sofosbuvir regimen centers on addressing the needs of HCV patient subpopulations who need new options even in light of the extraordinary advances that have occurred in HCV treatment,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “We look forward to working with the FDA toward the goal of eventually helping many difficult-to-treat HCV patients.”

Daklinza was initially approved in the U.S. in July 2015 and is indicated for use with sofosbuvir for the treatment of patients with chronic HCV genotype 3 infection. The new sNDAs accepted by the FDA for review include data from the ALLY-1 and ALLY-2 clinical trials. ALLY-2 evaluated the once-daily 12-week combination of Daklinza and sofosbuvir for the treatment of patients with HCV coinfected with HIV-1, a patient population that historically has been challenging to treat, in large part due to the complexities of the overlapping therapeutic regimens used to treat each infection. ALLY-1 evaluated a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with HCV with either advanced cirrhosis or post-liver transplant recurrence of HCV.

In May 2015, Daklinza with sofosbuvir received FDA Breakthrough Therapy Designation for HCV genotype 1 patients with advanced cirrhosis (Child-Pugh Class B or C) and those who develop genotype 1 HCV recurrence post-liver transplant. Breakthrough Therapy Designation, according to the FDA, is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for this designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

About Bristol-Myers Squibb in HCV

Bristol-Myers Squibb’s research efforts are focused on advancing compounds to deliver the most value to HCV patients with high unmet needs. At the core of our portfolio is Daklinza, a NS5A complex inhibitor which continues to be investigated in multiple treatment regimens and in patients with high disease burden.

In July 2014, Japan became the first country in the world to approve the use of a daclatasvir-based regimen for the treatment of chronic HCV. Since then, daclatasvir-based regimens have been approved in more than 50 countries, including the United States, across Europe, and in numerous other countries in Central and South America, the Middle East and the Asia-Pacific region.

Indication and Important Safety Information - Daklinza™ (daclatasvir)

INDICATION

Daklinza™ (daclatasvir) is indicated for use with sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) genotype 3 infection.

Limitations of Use:

Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Drugs Contraindicated with Daklinza: strong inducers of CYP3A that may lead to loss of efficacy of Daklinza include, but are not limited to:
Phenytoin, carbamazepine, rifampin, St. John’s wort (Hypericum perforatum).

WARNINGS and PRECAUTIONS

-- Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of Daklinza and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of Daklinza and possible development of resistance, dosage adjustments for other agents or Daklinza, possible clinically significant adverse events from greater exposure for the other agents or Daklinza.

Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported with ledipasvir/sofosbuvir.
Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.2 of the prescribing information.
Bradycardia generally resolved after discontinuation of HCV treatment.
Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.

ADVERSE REACTIONS

The most common adverse reactions were (≥ 5%): headache (14%), fatigue (14%), nausea (8%), and diarrhea (5%).

DRUG INTERACTIONS

CYP3A: Daklinza is a substrate. Moderate or strong inducers may decrease plasma levels and effect of Daklinza. Strong inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir) may increase plasma levels of Daklinza.
P-gp, OATP 1B1 and 1B3, and BCRP: Daklinza is an inhibitor, and may increase exposure to substrates, potentially increasing or prolonging their adverse effect.
See Section 7 of the Full Prescribing Information for additional established and other potentially significant drug interactions and related dose modification recommendations.

Daklinza in Pregnancy: No data with Daklinza in pregnant women are available to inform a drug-associated risk. Animal studies of Daklinza at exposure above the recommended human dose have shown maternal and embryofetal toxicity. Consider the benefits and risks of Daklinza when prescribing Daklinza to a pregnant woman.

Nursing Mothers: Daklinza was excreted into the milk of lactating rats; it is not known if Daklinza is excreted into human milk. Consider the benefits and risks to the mother and infant when breastfeeding.

Please click here for the Daklinza full prescribing information.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information please visit www.bms.com or follow us on Twitter at twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Daklinza will be approved for the additional indication mentioned above. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2014 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts
Bristol-Myers Squibb Company
Media:
Robert Perry, 609-419-5378
cell: 407-492-4616
rob.perry@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Bill Szablewski, 609-252-5894
william.szablewski@bms.com

September 2015 Mid-Month Edition - SNAPSHOTS —Alan Franciscus, Editor-in-Chief

This month’s Snapshots is about recently published studies on all-oral therapies to treat hepatitis C in people coinfected with HIV.  We have really come a long way in such a short period of time with medications to treat a population in high need of effective therapies.    
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Article: Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1—S Naggie et al.

Source:  New England Journal of Medicine DOI: 10.1056/NEJMoa1501315

Results and Conclusions
The study included 335 patients coinfected with HIV-1 and hepatitis C genotype 1 or 4.  The median age was 52 yo (48-58 yo).  The majority of patients were White 61% (203 pts) and Black 34% (115 pts), male 82% (276), genotype 1a 75%, genotype 4 two percent, cirrhosis 20%, median CD 4+ cell count 628 (469-823), treatment naïve 45%, previously treated 55%. The treatment period was 12 weeks.  Note: I am not including the genotype 4 patients since there were only 8 patients.  

The Bottom Line
The cure rates were 96% for genotype 1a, and 96% for genotype 1b. The cure rates were similar regardless of prior response or degree of liver damage.  The most common side effects were headache, fatigue and diarrhea.  No patients discontinued treatment due to side effects.

Editorial Comment
These results are excellent across subtypes (1a/1b), races, and prior treatment responses.  Gilead has filed for marketing approval with the Food and Drug Administration.  The American Association for the Study of Liver Disease (AASLD) and the Infectious Disease Society of America (IDSA) recommend Harvoni as a treatment for HCV for people coinfected with HIV and hepatitis C.

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Article: Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial—J K Rockstroh, et al

Source:  The Lancet HIV Volume 2, No. 8, e319–e327, August 2015

Results and Conclusions
The study was conducted in people with HIV/HCV coinfection to evaluate grazoprevir/elbasvir (one pill, once-a-day) to treat HCV genotype 1, 4, and 6. The treatment period was 12 weeks. There were 218 patients in the phase 3 trial.  The trial was conducted in Europe, the United States and Australia.

The Bottom Line
The overall cure rate was 96% (210 of 218 patients).  All patients who had cirrhosis were cured.  The most common side effects were fatigue, headache and nausea. No patients discontinued treatment due to side effects.

Editorial Comment
The high cure rates and fewer side effects plus no treatment discontinuation due to treatment-related side effects equals very good news for patients.

The once-a-day combination of grazoprevir/elbasvir when approved is going to be a welcome addition to the other therapies to treat hepatitis C in people who are HIV and HCV coinfected.  

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Article: Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1—D L Wyles et al.  
Source:  New England Journal of Medicine DOI: 10.1056/NEJMoa1503153

Results and Conclusions
There were 3 different treatment groups. All the groups received daclatasvir plus sofosbuvir. Note: Since there was a small number of genotype 2, 3, and 4 patients—I omitted these results.  For this article I am just listing the genotype 1 results.    

The Bottom Line
The patient characteristics, treatment durations and cure rates are included below:

1. Naïve (untreated patients): 101 patients; median age 52 yo; male sex 91%; race: White 65%, Black 30%; genotype 1a: 70%, genotype 1b: 12%; cirrhosis 9%; median CD4+ count 520 (122-1147). Treatment duration = 12 weeks. Cure rate = 96%
2. Naïve (untreated patients): 50 patients; median age 51 yo; male 84%; race White 56%, Black 38%; Genotype 1a 70%, Genotype 1b 12%; cirrhosis 10%; treatment duration = 8 weeks.  Cure rate = 76%
3. Treatment Experienced:  52 patients; median age 57 yo; male 83%; race White 60%, Black 38%; genotype 1a 63%, genotype 1b 21%; cirrhosis 29%; treatment duration =12 weeks.  Cure rate = 98%

The most common side effects were fatigue, nausea, and headache.  No patient discontinued due to side effects.

Editorial Comment
The 12-week treatment groups had good cure rates as opposed to the 8-week treatment response group.  The treatment-experienced group #3 with a 38% Black population and a relatively high cirrhotic population achieved nearly perfect cure rates. The drawback of this combination is going to be the high price tag of the combination of these two drugs.

Note:  Another issue with treating hepatitis C in people with HIV is the potential drug-drug interactions with HIV medications.  For more information visit the AASLD/IDSA  HCV Guidelines http://www.hcvguidelines.org/full-report-view.

UK:Hepatitis C patients in England denied lifesaving liver drug

Health experts concerned about decision not to extend Daklinza treatment to patients with genotype 3 strain of virus

Thousands of people in England with a chronic form of liver disease are being denied access to life-saving drugs that are available to patients in Wales, Scotland and Northern Ireland.

Despite being recommended by European regulators and available in countries such as France and Germany, draft guidance recently issued by the National Institute for Health and Care Excellence (Nice), the body that advises NHS England on whether to fund certain drugs, recommends restricting the use of Daklinza in England. The stance will affect the treatment of adult patients with a particular strain of hepatitis C.

The move has dismayed health experts and liver disease charities who say it will mean a large subset of the sickest and most at risk patients in England will not receive the treatment they need to prevent them from potentially fatal liver failure or cancer.

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2 New Easy C Treatment Fact Sheets

Be sure to check out these 2 new Easy C Facts fact sheets on treatment for Genotype 3 and Genotype 4

Click to Download

Click to Download