Regeneron Pharmaceuticals, Inc. (Public, NASDAQ:REGN)

[Michael Scally MD]

This stock, IMO, is overpriced, but it might just keep going! They have one FDA Approved drug ([ARCALYST® (rilonacept)].

IMO, a very exciting area is that for LDL cholesterol control. This is through PCSK9. I attached a recent PCSK9 review article. Quote: REGENERON recently communicated an interim efficacy analysis of a dose-escalating, randomized, double-blind, placebo-controlled, Phase 1 trial in healthy volunteers with its monoclonal antibody REG727. Both intravenous and subcutaneous routes of administration are being tested. A significant decrease of LDL-C, lasting over a month after a single dose, was reported with a maximum 60% decrease of mean LDL-C (Investor Day event, Regeneron Pharmaceuticals, Inc. - Regeneron Provides Initial Data on Two Antibody Product Candidates ).

PCSK9 Blockers: The Next Big Thing?
Insight: Next big drug against cholesterol takes shape | Reuters

Separate paths lead to promising cholesterol drug
http://www.reuters.com/article/2011/08/26/health-cholesterol-discovery-idUSN1E77O1IE20110826


Waiting, Watching, . . .


Regeneron Pharmaceuticals, Inc. (Public, NASDAQ:REGN) REGENERON
IR: REGENERON > Investor Relations

GF: Regeneron Pharmaceuticals, Inc.: NASDAQ:REGN quotes & news - Google Finance
YF: REGN: Summary for Regeneron Pharmaceuticals, Inc.- Yahoo! Finance
SA: Regeneron Pharmaceuticals, Inc. (REGN) Stock - Seeking Alpha

SEC: 0000872589 (see all company filings)


ARCALYST® (rilonacept) - For the Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS)
http://www.regeneron.com/arcalyst.html

In February 2008, the U.S. Food and Drug Administration (FDA) approved ARCALYST Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older.


Regeneron has 11 investigational product candidates progressing through all stages of human clinical trials for a diverse set of serious diseases including cancer, eye diseases, inflammatory diseases, pain, cardiovascular/metabolic diseases, and allergic conditions. The Company draws on strong internal capabilities and its collaborations with the sanofi-aventis Group and Bayer HealthCare to manage these significant clinical efforts. http://www.regeneron.com/pipeline.html


Regeneron and sanofi-aventis are collaborating on the discovery, development, and commercialization of fully human monoclonal antibodies generated using our Velocimmune® technology. http://www.regeneron.com/monoclonal_antibodies.html
These antibodies are in clinical development:

REGN727 (PCSK9 antibody) - An antibody to PCSK9, a novel target for LDL cholesterol reduction in patients with hyperlipidemia.

REGN88 (IL-6R antibody) - An antibody to the interleukin-6 receptor in development for the treatment of rheumatoid arthritis and ankylosing spondylitis.

REGN421 (Dll4 antibody) - An antibody to delta-like ligand-4 (Dll4) in development to disrupt angiogenesis in patients with cancer.

REGN668 (IL4R antibody) - An antibody to the Interleukin 4 receptor that modulates the effects of IL4 and IL13 in certain allergic and immune conditions.

REGN475 (NGF antibody) - An antibody to nerve growth factor (NGF), a novel target for the treatment of pain. Currently on clinical hold.

REGN910 - An antibody to angiopoietin-2 (ANG2), a novel angiogenesis target for inhibiting tumor growth in oncology.

REGN846 - Target undisclosed.

REGN728 - Target undisclosed.

 

[Michael Scally MD]

This stock is UP UP UP (~20%) since the original post!

 

[CubbieBlue]

This stock is UP UP UP (~20%) since the original post!

#2 biggest gainer of the day .

 

[Michael Scally MD]

Keep an "eye" on REGN for its LDL lowering mab.

Regeneron Shoots Up, Then Falls on Eye Drug
http://www.minyanville.com/businessmarkets/articles/regeneron-pharmaceuticals-eylea-roche-lucentis-avastin/9/9/2011/id/36805

Shares of Regenereon Pharmaceuticals (REGN) went on a tear since the beginning of the month. The stock jumped by more than a quarter since the end of August, peaking Thursday as it almost hit $75 a share.

Today, Regeneron is dropping as even bullish analysts note that the stock got ahead of itself. Shares fell 7% to $67.19 in late-morning trading. The stock has doubled this year.

What caused the recent burst of enthusiasm for this company, a maker of an experimental eye treatment? The investor sentiment had more to do with issues surrounding competitor Roche than any change in the Regeneron story.

NIH study finds Avastin and Lucentis are equally effective in treating age-related macular degeneration
NIH study finds Avastin and Lucentis are equally effective in treating age-related macular degeneration, April 28, 2011 News Release - National Institutes of Health (NIH)

Researchers are reporting results from the first year of a two-year clinical trial that Avastin, a drug approved to treat some cancers and that is commonly used off-label to treat age-related macular degeneration (AMD), is as effective as the Food and Drug Administration-approved drug Lucentis for the treatment of AMD.

The report, from the Comparison of AMD Treatments Trials (CATT), was published online in the New England Journal of Medicine on Sunday, May 1, 2011. CATT is funded by the National Eye Institute (NEI), a part of the National Institutes of Health.

Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011;364(20):1897-908. Ranibizumab and bevacizumab for neovascular age... [N Engl J Med. 2011] - PubMed - NCBI

BACKGROUND: Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data.

METHODS: In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.

RESULTS: Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 mum) than in the other groups (152 to 168 mum, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.

CONCLUSIONS: At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

 

[Michael Scally MD]

Regeneron $REGN shares jump as VA drops Avastin following infection/blindness reports; stock halted up 10%
https://twitter.com/#!/Street_Insider/status/116573947088207872

 

[Michael Scally MD]

This was announced on Friday. It was expected.

I am more closely watching its REGN727 (PCSK9 antibody) program. http://www.regeneron.com/monoclonal_antibodies.html [An antibody to PCSK9, a novel target for LDL cholesterol reduction in development in patients with hyperlipidemia.]


Regeneron Announces FDA Approval of EYLEA™ (Aflibercept) Injection for the Treatment of Wet Age-Related Macular Degeneration
http://newsroom.regeneron.com/releasedetail.cfm?ReleaseID=625372 (Regeneron Pharmaceuticals, Inc. - Multimedia: Regeneron Announces FDA Approval of EYLEA™ (Aflibercept) Injection for the Treatment of Wet Age-Related Macular Degeneration)

 

[Michael Scally MD]

The share price has gone from ~$55 to over $117 since this thread began!!!

Promising Phase 1 Results For New Monoclonal Antibody to PCSK9
Promising Phase 1 Results For New Monoclonal Antibody to PCSK9 - Forbes

 

[Michael Scally MD]

Long Term Reduction in Low-Density Lipoprotein Cholesterol Beginning Early in Life

Long Term Reduction in Low-Density Lipoprotein Cholesterol Beginning Early in Life - YouTube

http://clinicaltrialresults.org/Slides/ACC2012/Ference_BAFerence_LDLmRCT.pdf

 

[Michael Scally MD]

Antibodies to PCSK9: A Superior Way to Lower LDL Cholesterol?

Lowering of LDL cholesterol, predominantly accomplished clinically by statins, is one of the key components of both the prevention and medical management of coronary atherosclerosis; however, additional or alternative cholesterol lowering agents are needed for patients who fail to achieve goals or have adverse effects on statins. Owing to relatively rapid translation of basic science research on a novel regulatory pathway of the LDL receptor by PCSK9, a new class of such drugs with a different mode of action, and potentially better tolerance and less off-target effects may be just over the horizon.

Maxwell KN, Breslow JL. Antibodies to PCSK9: A Superior Way to Lower LDL Cholesterol? Circ Res 2012;111(3):274-7. Antibodies to PCSK9

 

[Michael Scally MD]

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

Giugliano RP, Desai NR, Kohli P, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase

BACKGROUND: LDL cholesterol (LDL-C) is a well established risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation. We therefore assessed the efficacy, safety, and tolerability of AMG 145, a human monoclonal IgG2 antibody against PCSK9, in stable patients with hypercholesterolemia on a statin.

METHODS: In a phase 2, dose-ranging study done in 78 centres in the USA, Canada, Denmark, Hungary, and Czech Republic, patients (aged 18-80 years) with LDL-C greater than 2.2 mmol/L on a stable dose of statin (with or without ezetimibe), were randomly assigned equally, through an interactive voice response system, to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, or matching placebo every 2 weeks; or subcutaneous injections of AMG 145 280 mg, 350 mg, or 420 mg, or matching placebo every 4 weeks. Everyone was masked to treatment assignment within the every 2 weeks and every 4 weeks schedules. The primary endpoint was the percentage change in LDL-C concentration from baseline after 12 weeks. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01380730.

FINDINGS: 631 patients with hypercholesterolaemia were randomly assigned to AMG 145 70 mg (n=79), 105 mg (n=79), or 140 mg (n=78), or matching placebo (n=78) every 2 weeks; or AMG 145 280 mg (n=79), 350 mg (n=79), and 420 mg (n=80), and matching placebo (n=79) every 4 weeks. At the end of the dosing interval at week 12, the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every 2 weeks (ranging from 41.8% to 66.1%; p<0.0001 for each dose vs placebo) and AMG 145 every 4 weeks (ranging from 41.8% to 50.3%; p<0.0001). No treatment-related serious adverse events occurred. The frequencies of treatment-related adverse events were similar in the AMG 145 and placebo groups (39 [8%] of 474 vs 11 [7%] of 155); none of these events were severe or life-threatening.

INTERPRETATION: The results suggest that PCSK9 inhibition could be a new model in lipid management. Inhibition of PCSK9 warrants assessment in phase 3 clinical trials. FUNDING: Amgen.


Koren MJ, Scott R, Kim JB, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study : The Lancet

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases serum LDL-cholesterol (LDL-C) concentrations. We assessed the effects of AMG 145, a human monoclonal antibody against PCSK9, in patients with hypercholesterolaemia in the absence of concurrent lipid-lowering treatment.

METHODS: In a phase 2 trial done at 52 centres in Europe, the USA, Canada, and Australia, patients (aged 18-75 years) with serum LDL-C concentrations of 2.6 mmol/L or greater but less than 4.9 mmol/L were randomly assigned equally through an interactive voice response system to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, or placebo every 2 weeks; subcutaneous AMG 145 280 mg, 350 mg, or 420 mg or placebo every 4 weeks; or oral ezetimibe 10 mg/day. The primary endpoint was percentage change from baseline in LDL-C concentration at week 12. Analysis was by modified intention to treat. Study personnel and patients were masked to treatment assignment of AMG 145 or placebo. Ezetimibe assignment was open label. This trial is registered with ClinicalTrials.gov, number NCT01375777.

FINDINGS: 406 patients were assigned to AMG 145 70 mg (n=45), 105 mg (n=46), or 140 mg (n=45) every 2 weeks; AMG 145 280 mg (n=45), 350 mg (n=45), or 420 mg (n=45) every 4 weeks; placebo every 2 weeks (n=45) or every 4 weeks (n=45); or ezetimibe (n=45). AMG 145 significantly reduced LDL-C concentrations in all dose groups (mean baseline LDL-C concentration 3.7 mmol/L [SD 0.6]; changes from baseline with every 2 weeks AMG 145 70 mg -41.0% [95% CI -46.2 to -35.8]; 105 mg -43.9% [-49.0 to -38.7]; 140 mg -50.9% [-56.2 to -45.7]; every 4 weeks AMG 145 280 mg -39.0% [-44.1 to -34.0]; 350 mg -43.2% [-48.3 to -38.1]; 420 mg -48.0% [-53.1 to -42.9]; placebo every 2 weeks -3.7% [-9.0 to 1.6]; placebo every 4 weeks 4.5% [-0.7 to 9.8]; and ezetimibe -14.7% [-18.6 to -10.8]; p<0.0001 for all doses vs placebo or ezetimibe). Treatment-emergent adverse events occurred in 136 (50%) of 271 patients in the AMG 145 groups, 41 (46%) of 90 patients in the placebo groups, and 26 (58%) of 45 patients in the ezetimibe group; no deaths or serious treatment-related adverse events were reported.

INTERPRETATION: The results of our study support the further assessment of AMG 145 in long-term studies with larger and more diverse populations including patients with documented statin intolerance. FUNDING: Amgen.

 

[Michael Scally MD]

Proprotein Convertase Subtilisin/Kexin type 9, also known as PCSK9, is an enzyme that in humans is encoded by the PCSK9 gene. Many enzymes are inactive when they are first synthesized, because they have a section of peptide chains that blocks their activity. Proprotein convertases remove that section to activate the enzyme. PCSK9 has medical significance because it acts in cholesterol synthesis. Drugs that block PCSK9 can lower cholesterol, and are beginning Phase III clinical trials to see if they can actually improve outcomes in heart disease.


Hypothetical Mechanisms Of PCSK9 Action In Hepatocyte With Possible Target Spots For Intervention With Antilipidemic Drugs

- indicates inhibition of PCSK9 activation/synthesis;
LDL – low-density lipoproteins;
PCSK9 – proprotein convertase subtilisin-like
kexin type 9; LDLR – LDL receptor;
SREBP-2 – sterol responsive element binding protein 2

 

[Stretch]

The share price has gone from ~$55 to over $117 since this thread began!!!

Promising Phase 1 Results For New Monoclonal Antibody to PCSK9
Promising Phase 1 Results For New Monoclonal Antibody to PCSK9 - Forbes

Good thing for them that I didn't buy any.

If it was raining pussy I would get hit by a dick.

Nice thread Doc.

 

[Michael Scally MD]

Behind The Scenes At Regeneron
An insider’s look at the Tarrytown-based pharmaceutical giant.
http://www.westchestermagazine.com/Westchester-Magazine/March-2015/Behind-The-Scenes-At-Regeneron/

 

[Michael Scally MD]

Regeneron and Sanofi Announce 18-Month Results of ODYSSEY LONG TERM Trial with Praluent™ (alirocumab) Published in The New England Journal of Medicine
Robust and consistent LDL-C lowering demonstrated with Praluent™ in largest, double-blind, placebo-controlled trial of a PCSK9 inhibitor to date
Fewer major cardiovascular events observed with Praluent™ in post hoc analysis
http://investor.regeneron.com/releaseDetail.cfm?ReleaseID=901604

TARRYTOWN, N.Y. and PARIS, March 15, 2015 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that 18-month (78-week) results of a Phase 3 trial of Praluent™ (alirocumab), an investigational therapy, involving 2,341 high risk patients with hypercholesterolemia were published online in The New England Journal of Medicine. In the ODYSSEY LONG TERM trial, Praluent 150 mg every two weeks reduced low-density lipoprotein cholesterol (LDL-C or "bad" cholesterol) by an additional 62 percent at week 24 when compared to placebo, the primary efficacy endpoint of the study, with consistent LDL-C lowering maintained over 78 weeks.