Pipeline Drugs

Medications to treat the risk factors for Coronary Artery Disease (CAD), such as high cholesterol -- The most commonly prescribed high cholesterol medications are the statins. The approved Statin options that are generally prescribed by doctors are atorvastatin (Lipitor), fluvastatin (Lescol), rosuvastatin (Crestor), pitavastatin (Livalo), simvastatin (Zocor), lovastatin (Altoprev, Mevacor) and pravastatin (Pravachol). Statins have been a mainstay of heart attack and stroke prevention for the past 20 years, but the race is on to bring a new drug to market that targets an enzyme called PCSK9. The PCSK9 inhibitors are a new class of drugs that have been shown to dramatically lower LDL cholesterol levels. PCSK9 inhibitors are monoclonal antibodies (MABs), a type of biologic drug. They inactivate a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9) Pipeline Drugs for PCSK9 --Pfizer is currently developing PCSK9 pill and vaccine to lower cholesterol . Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) and is from Amgen. Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. See: FDA approves Repatha (evolocumab) to treat certain patients with high cholesterol. Amgen's low-density lipoprotein cholesterol-lowering medication is in direct competition with Sanofi/RegeneronPharmaceuticals's alirocumab. See: FDA approves Praluent (alirocumab) to treat certain patients with high cholesterol. Industry analysts forecast billions of dollars of peak annual sales for both products. Studies using a vaccine to lower cholesterol are still in the pipeline.

Congestive Heart Failure (CHF), occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the body's needs. Common causes of heart failure include coronary artery disease including a previous myocardial infarction (heart attack), high blood pressure, atrial fibrillation, valvular heart disease, excess alcohol use, infection, and cardiomyopathy of an unknown cause. Enresto by Novartis was approved in July 2015. Entresto is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. Entresto is specifically indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. Bayer is pushing forward with a new heart-failure treatment that could eventually contend with Novartis' ($NVS) blockbuster-in-waiting Entresto, mapping out a wide Phase III program for its oral drug. The pill, finerenone, is a next-generation mineralocorticoid receptor antagonist, or MRA, designed to block the production of bodily steroids that degrade heart function and lead to kidney problems. Amgens, omecamtiv mecarbil --is a cardiac-specific myosin activator. It is being studied for a potential role in the treatment of left ventricular systolic heart failure.




Checkpoint inhibitors --Immune checkpoints are molecules in the immune system that either turn up a signal (co-stimulatory molecules) or turn down a signal. Since around 2010 inhibitory checkpoint molecules have been increasingly considered as new targets for cancer immunotherapies due to the effectiveness of two checkpoint inhibitor drugs that were initially indicated for advanced melanoma:. ipilimumab ( Yervoy), from Bristol-Myers Squibb, and Pembrolizumab (Keytruda), from Merck. Keytruda (Pembrolizumab, formerly MK-3475) , is a humanized antibody used in cancer immunotherapy. It targets the programmed cell death 1 (PD-1) receptor. ipilimumab,(Yervoy) which was the first FDA-approved immune checkpoint inhibitor blocks the CTLA-4 molecule on T cells, which leads to a broad enhancement of immune responses, including attacks on cancer cells. A range of newer drugs targets a different immune checkpoint protein known as PD-1. The treatments work by preventing cancer cells from attaching to the PD-1 protein on immune cells, which leads to an increased antitumor immune response and generally fewer adverse effects. See Full Text and list of Checkpoint Inhibitors

Cell division blockers-


Kinase inhibitors including tyrosine kinase --Tyrosine kinase inhibitors also called TKIs. They block chemical messengers called tyrosine kinases. Tyrosine kinases help to send growth signals in cells. So blocking them stops the cell growing and dividing. Cancer growth blockers can block one type of tyrosine kinase or more than one type. TKIs that block more than one type of tyrosine kinase are called multi-TKIs. Ibrutinib (Imbruvica), Crizotinib (trade name Xalkori, Pfizer) ,Acalabrutinib (rINN, ACP-196) , Acerta Pharma... see Full List on Kinase and tyrosine inhibitors.

mTOR Inhibitors--Mammalian target of rapamycin (mTOR) is a serine/threonine kinase, which belongs to phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs) family. It regulates cellular metabolism, growth, and proliferation, and therefore is a target for the development of a number of mTOR inhibitors. LY3023414 is a small molecule that has been shown in vitro to be a selective ATP-competitive inhibitor of PI3Kα and mTOR, DNA-PK, and other class I PI3K family members.

PI3K inhibitors--A phosphoinositide 3-kinase inhibitor (PI3K inhibitor) is a class of drug that functions by inhibiting one or more of the phosphoinositide 3-kinase enzymes, which are part of the PI3K/AKT/mTOR pathway, an important signalling pathway for many cellular functions such as growth control, metabolism and translation. See PI3K inhibitors.

Proapoptotic Small Molecule Drugs--Bcl-2 inhibitors/pathways--Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy--Inhibition of pro-survival proteins of the BCL family is a promising anti-cancer strategy. Venetoclax (AbbVie/Genentech) –is an oral treatment for certain patients with chronic lymphocytic leukemia. Venetoclax acts as a Bcl-2 inhibitor. Read more...

Histone deacetylase inhibitors--Histone deacetylases are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. Histone deacetylase inhibitors removes acyl groups from histones which inhibit cancer cells from growing and dividing.

Entinostat (Syndax Pharmaceuticals) – an oral medication for certain types of breast cancer. Entinostat, also known as SNDX-275 and MS-275, is a benzamide histone deacetylase inhibitor undergoing clinical trials for treatment of various cancers.

Hedghog pathway inhibitors--The Hh signaling pathway has recently been recognized to be one of the most important signaling pathways and a therapeutic target in cancer. In adults, mutation or deregulation of this pathway plays a key role in both proliferation and differentiation leading to tumorigenesis or tumor growth acceleration in a wide variety of tissues. GDC-0449 (vismodegib) - Vismodegib (trade name Erivedge).

Proteasome inhibitors --Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. Proteasome inihibitors cause a buildup in unwanted proteins in the cell, which makes the cancer cells die. Bortezomib.(Velcade) ... read more


There are different types of drugs that block blood vessel growth, including: Drugs that block blood vessel growth factor, drugs that block signalling within the cell, drugs that affect signals between cells and drugs that block blood vessel growth factor. Some drugs block vascular endothelial growth factor (VEGF) from attaching to the receptors on the cells that line the blood vessels. This stops the blood vessels from growing. A drug that blocks VEGF is bevacizumab (Avastin. It is also a monoclonal antibody. See Reference 15. The FDA has approved several other drugs that have antiangiogenic activity, including sorafenib (Nexavar®), sunitinib (Sutent®), pazopanib (Votrient®), and everolimus (Afinitor®).


PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) that utilizes recombinant poxviruses to express PSA. It is a cancer immunotherapy candidate in clinical development by Bavarian Nordic for the treatment of metastatic castration-resistant prostate cancer (mCRPC)... read more

TARGETING CANCER STEM CELLS AND METASTASIS-- Demcizumab from Celgene/OncoMed blocks Delta-like ligand 4 (DLL4), a ligand of Notch receptors. Notch signaling has been implicated as a key signaling pathway in cancer stem cells. By treating patients with a combination of Demcizumab and a cytotoxic chemotherapy, it is hoped that a more durable anti-tumor response can be achieved than with chemotherapy alone. Salinomycin has been shown by Piyush Gupta et al. of the Massachusetts Institute of Technology and the Broad Institute to kill breast cancer stem cells in mice at least 100 times more effectively than the anti-cancer drug paclitaxel. The study screened 16,000 different chemical compounds and found that only a small subset, including salinomycin and etoposide, targeted cancer stem cells responsible for metastasis and relapse.

SB202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α/β with IC50 and U0126 is a highly selective inhibitor of both MEK1 and MEK2, a type of MAPK/ERK kinase. See full Cancer page.

DRUGS TO TARGET WARBURG HYPOTHESIS --Malignant cells exhibit aerobic glycolysis (the Warburg effect) and become dependent on de novo lipogenesis, which sustains rapid proliferation and resistance to cellular stress. The nuclear receptor liver-X-receptor (LXR) directly regulates expression of key glycolytic and lipogenic genes. To disrupt these oncogenic metabolism pathways, we designed an LXR inverse agonist SR9243 that induces LXR-corepressor interaction. In cancer cells, SR9243 significantly inhibited the Warburg effect and lipogenesis by reducing glycolytic and lipogenic gene expression. SR9243 induced apoptosis in tumors without inducing weight loss, hepatotoxicity, or inflammation. Our results suggest that LXR inverse agonists may be an effective cancer treatment approach. SEE FULL CANCER PAGE HERE...

Diseases and conditions of the respiratory system can be divided into two categories: 1) Viruses such as influenza, bacterial pneumonia and the new enterovirus respiratory virus that has been diagnosed in children; and 2) chronic diseases, such as asthma and chronic obstructive pulmonary disease (COPD).

Asthma --Mepolizumab1,2 is a humanized monoclonal antibody that recognizesinterleukin-5 (IL-5) .Benralizumab,3 an anti-IL-5 receptor α-monoclonal antibody which seemed to reduce asthma exacerbations in adults.Reslizumab,4 humanized anti-IL-5 monoclonal antibody, has results that support its use in patients with asthma and elevated blood eosinophil counts. Dupilumab,5 a fully human monoclonal antibody that blocks IL-4 and IL-13, has shown efficacy in patients with asthma and elevated eosinophil levels. Genentech's Lebrikizumab (INN) is a humanized monoclonal antibody--Genentech snags a PhII-ready IL-33 asthma/COPD drug from Amgen.


FF/UMEC/VI: Triple Combination Therapy--GSK Announces COPD Drug Achieves Late-Stage Study Goals --once-daily 'closed' triple combination therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI: a combination inhaled corticosteroid, long-acting muscarinic antagonist, long-acting beta agonist), in patients with chronic obstructive pulmonary disease (COPD).SAMA Glycopyrrolate Sunovion 3 (recruiting) LAMA Glycopyrronium bromide Novartis 3 (some complete, others recruiting) LAMA/LABA Olodaterol/tiotropium bromide Boehringer-Ingelheim 3 (complete) Indacaterol/glycopyrronium bromide Novartis, Anti-IL-5 monoclonal antibodies Benralizumab AstraZeneca 3 (recruiting) Mepolizumab GlaxoSmithKline

Short-acting muscarinic antagonists (SAMAs) are a mainstay of treatment for COPD, but these medications must be inhaled multiple times daily. Newer longacting agents may help improve adherence through once-daily administration. These long-acting muscarinic antagonists (LAMAs) include tiotropium and aclidinium. One LAMA (glycopyrronium bromide) and 1 SAMA (glycopyrrolate) are in late-stage development as treatments for COPD. SEE FULL RESPIRATORY DISEASE PAGE

Stroke is a disease that affects the arteries leading to and within the brain. It is theNo. 5 cause of death and a leading cause of disability in the United States. A stroke occurs when a blood vessel that carries oxygen and nutrients to the brain is either blocked by a clot or bursts (or ruptures). is the number no 5 cause of death In the acute phase of treatment drugs can be administered that minimize damage to the brain. Clot dissolvers, such as thrombolytic agents, are most effective when used within three hours of a thrombotic or an embolic stroke. There also are new treatments in the pipeline: Clinical trials are underway on several drugs designed to protect brain tissues after a stroke occurs. Further, preliminary studies with techniques that chill the brain have shown that inducing hypothermia may reduce stroke damage.

Clot-busting therapy reduces mortality in deadliest form of stroke The drug Alteplase, a tissue plasminogen activator, or tPA, cleared blood that pooled in the brains of people with intraventricular hemorrhage, reducing death rates by 10 percent and nearly doubled the likelihood of a more functional recovery, researchers reported at the 2016 International Stroke Conference.

Ambien -- Stroke recovery in mice improved by Ambien, study shows-Zolpidem, better known by the trade name Ambien, increased the rate at which mice that had strokes recovered their pre-stroke sensory acuity and motor coordination.
Intravenous tissue plasminogen activator (tPA) remains the only level 1A treatment for acute ischemic stroke. It is the only FDA approved treatment for ischemic strokes is tissue , (given through an IV in the arm). tPA works by dissolving the clot and improving blood flow to the part of the brain being deprived of blood flow. If administered within 3 hours(and up to 4.5 hours in certain eligible patients), tPA may improve the chances of recovering from a stroke. A significant number of stroke victims don't get to the hospital in time for tPA treatment; this is why it's so important to identify a stroke immediately.
Magnetic nanoparticles could stop blood clot-caused strokes ---By loading magnetic nanoparticles with drugs and dressing them in biochemical camouflage, researchers say they can destroy blood clots 100 to 1,000 times faster than a commonly used clot-busting technique. SEE FULL STROKE PAGE

Alzheimer's is a progressive mental deterioration that can occur in middle or old age, due to generalized degeneration of the brain. It is the most common cause of premature senility. Although scientists are not absolutely sure what causes Alzheimer's plaques, tangles and inflammation are prime suspects in cell death and tissue loss in the Alzheimer brain.

There are currently 5 drugs approved for Alzheimer's, (Aricept, Razadyne, Namenda, Exelon and Namzaric). The last drug to be approved -Namzaric- was in 2014. The current Alzheimer's drugs only mask the symptoms but do not treat the underlying disease.


Beta-secretase drugs and monoclonal antibodies are currently being tested to target beta-amyloid. See reference 8--After a string of failed trials, drugs that target protein build-up in the brain appear to slow disease progress.

Antibodies targeting Amyloid Plaque

Aducanumab -- Biogen-- monoclonal antibody that targets aggregated forms of beta amyloid. Gantenerumab -- Roche+/-One clinical study was stopped on December 19, 2014 after disappointing results. Crenezumab -- Genentech and Roche --Crenezumab is a humanized monoclonal antibody against human 1-40 and 1-42 Beta amyloid, which is being investigated as a treatment of Alzheimer's disease. Crenezumab was developed by the Swiss-based biopharmaceutical company AC Immune, which licensed the drug in 2006 to Genentech, Inc. Solanezumab -- Eli Lilly --Solanezumab, or sola, binds the amyloid-β peptides that aggregate and form plaques in the brain that are an early pathological feature of Alzheimer's disease. Sola binds the central epitope of monomeric amyloid-β, KLVFFAD, (PDB ID 4XXD) with picomolar affinity. This epitope is known as the nucleation site for Aβ oligomerization, and it is these oligomers of Aβ that are thought to be toxic to neurons.

Beta Secretase inhibitors (BACE)

Small molecule BACE inhibitors

MK-8931 is a BACE inhibitor from Merck See Reference 3-- it inhibits the ability of the beta-secretase enzyme to make beta-amyloid. At the Alzheimer’s Association International Conference® 2013 (AAIC®), researchers reported that the drug significantly lowered beta-amyloid levels in people with mild-to-moderate Alzheimer’s. MK-8931 is being tested in two phase 3 clinical trials. CNP520--Novartis' CNP520 is an oral drug designed to prevent the production of different forms of amyloid and has the potential to prevent, slow or delay the symptoms associated with Alzheimer's disease. AZD3293--AstraZeneca is codeveloping with Eli Lilly AZD3293 --also known as LY3314814 is an oral beta-secretase 1 cleaving enzyme (BACE) inhibitor. A pivotal Phase II/III clinical trial of AZD3293 started in late 2014 and is planned to recruit 1,500 patients and end in May 2019] In April 2016 the company announced it would advance to phase 3 without modification.

Targeting Tau Tangles and more..

NPT088 from Neurophage binds with high affinity and specificity to aggregates of misfolded proteins, including those that form the canonical amyloid motif, which is implicated in the pathology of many serious diseases such as AD and PD. NPT088 recognizes the special conformation characteristic of amyloids, irrespective of the specific protein sequence. NPT088 which simultaneously targeting multiple misfolded proteins such as amyloid beta, tau, and alpha-synuclein at various stages of amyloid assembly in both Alzheimer's disease and Parkinson's disease.

TRV-101-Treventis Corporation, Toronto, ON, Canada presented data on TRV 101, a new drug designed to enter the brain and inhibit protein misfolding of beta-amyloid and tau.


Experimental drug based on Curcumin

J147 - A new Alzheimers-reversing drug based on curcumin extract. Salk team finds molecule that slows the clock on key aspects of aging in animals---- A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease --The neurotrophic and memory-enhancing activities of J147 are associated with an increase in brain derived neurotrophic factor (BDNF) levels and the expression of BDNF responsive proteins, the enhancement of LTP, synaptic protein preservation, the reduction of markers for oxidative stress and inflammation, the reduction of amyloid plaques, and lower levels of soluble Aβ1–42 and Aβ1–40. These pleiotrophic effects of a single molecule suggest that J147 has potential for the treatment of AD.

Mefenamic Acid -- University of Manchester found that mefenamic acid, a common non-steroidal anti-inflammatory drug (NSAID) that's used for period pain, completely reversed memory loss and brain inflammation in mice.


Progress in world's first Alzheimer's vaccine --In research findings just released in Nature's Scientific Reports journal, Flinders University experts, as part of a high-level U.S. research team at the Institute of Molecular Medicine (IMM) and University of California, Irvine (UCI), have made a successful vaccine formulation that targets the abnormal beta-amyloid and tau proteins that signal Alzheimer's disease. It is actually two separate potential vaccines, one for beta-amyloid and one for tau proteins, have been combined to form the new treatment. The second tau vaccine candidate is the most recent to be discovered and is the most effective at reversing damage in the brain. The beta-amyloid one works best if it's given as a preventative measure for those at risk of dementia. Combined, the two drugs are even more effective, based on recent tests carried out on groups of mice. See Reference 13.


Human form of the C1q-blocking antibody is now at an early stage of development at Annexon Biosciences, a biotech company based in San Francisco.n the mouse models of Alzheimer’s, the team found that synapse loss requires activation of the protein C1q, which “tags” synapses for elimination. C1q became visibly more abundant around vulnerable synapses in the mice. Cells known as microglia then came in and “ate” the tagged synapses, as they do during normal brain development. SEE FULL ALZHEIMER'S PAGE


Protease inhibitors (PIs) are a class of antiviral drugs that are widely used to treat HIV/AIDS and hepatitis caused by hepatitis C virus. Protease inhibitors prevent viral replication selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.

Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:

HIV/AIDS: antiretroviral protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir.)
Hepatitis C: boceprevir, telaprevir , simeprevir

See also: HIV Treatment Pipline -- New Antiretroviral treatments: Two-drug oral combos. ViiV Healthcare and Janssen have begun Phase III trials of an oral two-drug regimen including Tivicay (dolutegravir) and Edurant (rilpivirine). Long acting treatment: A long-acting injectable formulation of ViiV's cabo-tegravir and Janssen's Edurant showed promise in a recent Phase IIb study... Monoclonal antibody treatment: VRC01, PRO 140 and ibalizumab.

Zika Vaccine --Inovio Pharmaceuticals and GeneOne Life Science Receive Approval for First-in-Man Zika Vaccine Clinical Trial -- June 2016--have received approval to initiate a phase I human trial to evaluate Inovio’s Zika DNA vaccine (GLS-5700) to prevent infection from this concerning virus.Read more on Zika Vaccine

Diabetes is a metabolic disease in which the body's inability to produce any or enough insulin causes elevated levels of glucose in the blood.-Type 1 diabetes --

Treatment typically begins with oral metformin, a veteran drug that is the backbone of many diabetes treatment regimens. Metformin should be the first-line drug for managing type 2 diabetes. Insulin and sulfonylureas should be second line, and glitazones should be reserved for third line. Metformin is the only drug for type 2 diabetes that does not cause weight gain, which is an important advantage. Insulin injected subcutaneously is the first-line treatment of type 1 diabetes mellitus.

Perhaps the biggest lingering R&D question involves late-stage biosimilars like Merck/Samsung Bioepis's MK-1293. MK-1293 is a generic version of Sanofi's top-selling insulin treatment Lantus (glargine)-- a $7 billion annual market.

Artificial Pancreas from Medronics could hit the market by 2017 --Medtronic has reportedly filed for FDA approval of an “artificial pancreas” that could transform diabetes care.


Current treatment for pain makes use of nonsteroidal anti-inflammatory medications (NSAIDs),, antidepressants, anticonvulsive medications, muscle relaxants and opiods.

Conotoxins from Snail Cones-

Conotoxins are small peptides that interact with the nervous systems of mammals in several ways, most notably by disrupting the activity of ion channels, including sodium, calcium and potassium channels involved in the transmission of pain signals. It is this ability of conotoxins to block pain. Conotoxins so far identified as potential analgesics target different receptors than those targeted by opioids. Ziconotide is one peptide approved by the FDA. Ziconotide however can only be administered via an injection into the spinal cord. Current research is underway to simplify conotoxins to make them more viable (orally administered).


Inflammation is the body's attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens - and begin the healing process.

--heart disease, diabetes, Alzheimer's, stroke and cancer have in common? Scientists have linked each of these to a condition known as chronic inflammation,

Brodalumab is another possible market success for Amgen that is being developed in collaboration with AstraZeneca. The novel human monoclonal antibody binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 ligands to the receptor. By stopping IL-17 ligands from activating the receptor, brodalumab prevents the body from receiving signals that may result in inflammation. The IL-17 pathway plays a main role in inducing and promoting inflammatory disease processes.

IL-10 --Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine.

ABP 501 is Amgen's biosimilar drug designed to compete with AbbVie's anti-inflammatory drug Humira.


With Baby Boomers ready to spend billions on aging, big pharma has been ...entrepreneurs are aiming to rebuild, regenerate and reprogram patients' organs, limbs, cells and DNA so people will be able live longer and better.

As of 2015 metformin was under study for its potential effect on slowing aging in the worm C.elegans and the cricket.[145] Its effect on otherwise healthy humans is unknown.[145] Trials in this area are underway including the Metformin in Longevity Study (MILES)[146] and the Targeting Aging with Metformin (TAME) study.[147]