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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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FDA approves Repatha to treat certain patients with high cholesterol


08/27/2015 05:10 PM EDT
The U.S. Food and Drug Administration today approved Repatha (evolocumab) injection for some patients who are unable to get their low-density lipoprotein (LDL) cholesterol under control with current treatment options.

August 27, 2015

Release

The U.S. Food and Drug Administration today approved Repatha (evolocumab) injection for some patients who are unable to get their low-density lipoprotein (LDL) cholesterol under control with current treatment options.

Repatha, the second drug approved in a new class of drugs known as PCSK9 inhibitors, is approved for use in addition to diet and maximally-tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH), homozygous familial hypercholesterolemia (HoFH), or clinical atherosclerotic cardiovascular disease, such as heart attacks or strokes, who require additional lowering of LDL cholesterol.

Familial hypercholesterolemia (encompassing both HeFH and HoFH) is an inherited condition that causes high levels of LDL cholesterol. A high level of LDL cholesterol in the blood is linked to cardiovascular or heart disease. Heart disease is the number one cause of death for Americans, both men and women. According to the Centers for Disease Control and Prevention, about 610,000 people die of heart disease in the United States every year– that equals one in every four deaths.

“Repatha provides another treatment option in this new class of drugs for patients with familial hypercholesterolemia or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough with statins,” said John Jenkins, M.D., director of the Office of New Drugs, Center for Drug Evaluation and Research. “Cardiovascular disease is a serious threat to the health of Americans, and the FDA is committed to facilitating the development and approval of effective and safe drugs to address this important public health problem.”

Repatha is an antibody that targets a specific protein, called PCSK9. PCSK9 reduces the number of receptors on the liver that remove LDL cholesterol from the blood. By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels.

The efficacy and safety of Repatha were evaluated in one 52-week placebo-controlled trial and eight 12-week placebo-controlled trials in participants with primary hyperlipidemia, including two that specifically enrolled participants with HeFH and one that enrolled participants with HoFH. In one of the 12-week studies, 329 participants with HeFH, who required additional lowering of LDL cholesterol despite statins with or without other lipid-lowering therapies, were randomized to receive Repatha or placebo for 12 weeks. Participants taking Repatha had an average reduction in LDL cholesterol of approximately 60 percent, compared to placebo.

The most common side effects of Repatha include nasopharyngitis, upper respiratory tract infection, flu, back pain, and reactions such as redness, pain, or bruising where the injection is given. Allergic reactions, such as rash and hives, have been reported with the use of Repatha. Patients should stop using Repatha and get medical help if they experience symptoms of a serious allergic reaction.

Multiple clinical trials have demonstrated that statins lower the risk of having a heart attack or stroke. A trial evaluating the effect of adding Repatha to statins for reducing cardiovascular risk is ongoing.

Repatha is marketed by Amgen Inc., of Thousand Oaks, Calif.

Japanese filing for Amgen’s PCSK9 inhibitor Repatha


Amgen has filed its closely watched PCSK9 inhibitor Repatha (evolocumab) in Japan for the treatment of high cholesterol.

Repatha is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C), or ‘bad’ cholesterol, from the blood.

Evolocumab

Monoclonal antibody
Type Whole antibody
Source Human
Target PCSK9
Clinical data
  • Investigational
Subcutaneous injection
Identifiers
1256937-27-5
C10AX13
Chemical data
Formula C6242H9648N1668O1996S56
141.8 kDa

Evolocumab[1] (also known as compound number AMG-145 or AMG145)[2] is a monoclonal antibody designed for the treatment of hyperlipidemia.[3] Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).

PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver’s ability to remove LDL-C, or “bad” cholesterol, from the blood.

Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.

Clinical trials

Two trials have been in progress as at mid-2014:

On 23 January 2014 Amgen announced that the Phase 3 GAUSS-2 (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2) trial evaluating evolocumab in patients with high cholesterol who cannot tolerate statins met its co-primary endpoints: the percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. The mean percent reductions in LDL-C, or “bad” cholesterol, compared to ezetimibe were consistent with results observed in the Phase 2 GAUSS study.[4][5]

The GAUSS-2 trial evaluated safety, tolerability and efficacy of evolocumab in 307 patients with high cholesterol who could not tolerate effective doses of at least two different statins due to muscle-related side effects. Patients were randomly assigned to one of four treatment groups: subcutaneous evolocumab 140 mg every two weeks and oral placebo daily; subcutaneous evolocumab 420 mg monthly and oral placebo daily; subcutaneous placebo every two weeks and oral ezetimibe 10 mg daily; or subcutaneous placebo monthly and oral ezetimibe 10 mg daily.

Safety was generally balanced across treatment groups. The most common adverse events (> 5 percent in evolocumab combined group) were headache (7.8 percent evolocumab; 8.8 percent ezetimibe), myalgia (7.8 percent evolocumab; 17.6 percent ezetimibe), pain in extremity (6.8 percent evolocumab; 1.0 percent ezetimibe), and muscle spasms (6.3 percent evolocumab; 3.9 percent ezetimibe).

Cholesterol-lowering treatment with a statin as part of follow-up care can help reduce a patient’s risk after myocardial infarction, ischaemic stroke or TIA.

The FOURIER Phase 3 clinical study http://www.fourierstudy.com/ seeks to find out whether lowering cholesterol by an additional 50% might reduce this risk even further. Several sites in the UK are part of this very large clinical study, lasting up to five years, and it is hoped that the study will help guide future clinical practice.

Evolocumab (also formerly known as AMG145, from Amgen) binds to PCSK9, a natural protein produced by the liver. By binding to PCSK9, evolocumab allows the LDL receptor (a protein present in the liver) to move LDL-cholesterol out of the bloodstream more efficiently. This study is designed to see whether treatment of dyslipidemia with evolocumab in people who have experienced a prior myocardial infarction, ischaemic stroke or TIA, and who are taking a highly effective dose of a statin, reduces the risk of recurring or additional cardiovascular events. Participants in this study have clinically evident cardiovascular disease.

READ AT

https://newdrugapprovals.org/2014/03/19/amgen-drug-evolocumab-hits-endpoint-of-cholesterol-reduction/

MY EARLIER ARTICLE

DR ANTHONY MELVIN CRASTO Ph.DDR ANTHONY CRASTO

https://newdrugapprovals.org/

References

 1

Pierson, Ransdell (17 March 2014). “Amgen drug meets goal for those with high genetic cholesterol”. Associated Press. Retrieved 19 March 2014.

Amgen Drug Evolocumab Hits Endpoint of Cholesterol Reduction


Amgen announced that the Phase 3 TESLA (Trial Evaluating PCSK9 Antibody in Subjects with LDL Receptor Abnormalities) trial evaluating evolocumab met its primary endpoint of the percent reduction from baseline at week 12 in low-density lipoprotein cholesterol (LDL-C). The percent reduction in LDL-C, or “bad” cholesterol, was clinically meaningful and statistically significant………….read at
Evolocumab 
Monoclonal antibody
Source Human
Target PCSK9
Clinical data
Legal status  ?
Identifiers
CAS number 1256937-27-5
ATC code None
Chemical data
Formula C6242H9648N1668O1996S56 
Mol. mass 141.8 kDa

Evolocumab[1] is a monoclonal antibody designed for the treatment of hyperlipidemia.[2] Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).

PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver’s ability to remove LDL-C, or “bad” cholesterol, from the blood.

Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.

On 23 January 2014 Amgen announced that the Phase 3 GAUSS-2 (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2) trial evaluating evolocumab in patients with high cholesterol who cannot tolerate statins met its co-primary endpoints: the percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. The mean percent reductions in LDL-C, or “bad” cholesterol, compared to ezetimibe were consistent with results observed in the Phase 2 GAUSS study.[3]

The GAUSS-2 trial evaluated safety, tolerability and efficacy of evolocumab in 307 patients with high cholesterol who could not tolerate effective doses of at least two different statins due to muscle-related side effects. Patients were randomized to one of four treatment groups: subcutaneous evolocumab 140 mg every two weeks and oral placebo daily; subcutaneous evolocumab 420 mg monthly and oral placebo daily; subcutaneous placebo every two weeks and oral ezetimibe 10 mg daily; or subcutaneous placebo monthly and oral ezetimibe 10 mg daily.

Safety was generally balanced across treatment groups. The most common adverse events (> 5 percent in evolocumab combined group) were headache (7.8 percent evolocumab; 8.8 percent ezetimibe), myalgia (7.8 percent evolocumab; 17.6 percent ezetimibe), pain in extremity (6.8 percent evolocumab; 1.0 percent ezetimibe), and muscle spasms (6.3 percent evolocumab; 3.9 percent ezetimibe).

Evolocumab, a PCSK9 inhibitor, was safe and effective at lowering low-density lipoprotein cholesterol (LDL-C) after one year of treatment, according to a study published online Nov. 19 inCirculation and presented simultaneously at the American Heart Association scientific session in Dallas.

The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER) trial took place at 156 study centers around the world that participated in at least one of four phase 2 studies of between October 2011 and June 2012. Evolocumab is a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor made by Amgen.

Investigators led by Michael J. Koren, MD, of the Jacksonville Center for Clinical Research in Florida, randomized 1,104 participants in a 2:1 ratio to receive either evolocumab (420 mg every four weeks) plus standard-of-care therapy (based on guidelines for treatment of hypercholesterolemia) or evolocumab alone, which served as the control. After 12 weeks, lipid results were unblinded and investigators were able to adjust standard-of-care therapy in either group.

The main efficacy objective was to determine the effects of longer-term evolocumab therapy on cholesterol levels and the main safety endpoints included incidence of adverse events, serious adverse events and adverse events resulting in discontinuation of the drug.

Patients who received evolocumab for the first time in the OSLER study had an average LDL-C reduction of 52.3 percent at one year. Patients previously dosed with evolocumab in a prior trial and were in the evolocumab and standard-of-care group in OSLER had an average LDL-C reduction of 52.1 percent at the end of the study compared with 50.4 percent at baseline. Patients who terminated evolocumab when they entered OSLER had their LDL-C levels returned to around their baseline.

Adverse events occurred in 73.1 percent of the standard-of-care group and 81.4 percent of the evolocumab plus standard-of-care group. The researchers determined that 5.6 percent of adverse events were related to evolocumab. Serious adverse events occurred in 6.3 percent of the control group and 7.1 percent in the combination group.

The authors explained that their findings offer more insight into the use of this class of drugs to lower LDL-C in at-risk patients.

“Challenging patients such as those who fail to reach current lipid goals despite maximum doses of highly effective statin agents or those with well-documented statin intolerance are thus logical populations for treatment with PCSK9 inhibitors,” they concluded.

References

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