Aramchol (arachidyl amido cholanoic acid; Galmed) is a conjugate of cholic acid and arachidic acid, and belongs to the synthetic fatty acid bile acid conjugates (FABACs) family. Aramchol inhibits the liver enzyme stearoyl-CoA desaturase 1 inhibitor (SCD1), and as a result fatty acid synthesis is reduced while fatty acid oxidation is increased. Additionally, Aramchol has hypocholesterolemic effects due to the upregulation of ATP-binding cassette transporter 1 (ABCA1). Ultimately, Aramchol causes incomplete SCD inhibition while also being anti-atherogenic.
Ocaliva (obeticholic acid; Intercept Pharmaceuticals) is a selective farnesoid X receptor (FXR) agonist. FXR is a nuclear bile acid receptor involved in the regulation of bile acids, lipids, and possibly glucose. Ocaliva is a derivative of chenodeoxycholic acid, the endogenous FXR agonist found naturally in human bile acid. By activating FXR, Ocaliva improves insulin sensitivity and inhibits lipogenesis, which reduces fat buildup in the liver and results in decreased inflammation. Ocaliva has also been linked to weight loss. Ocaliva is currently approved in the US and EU for primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.
Elafibranor (Genfit) is an oral peroxisome proliferator-activated receptor (PPAR) alpha-delta dual agonist. The medication activates PPAR-alpha and PPAR-delta, which control gene expression. Stimulating these receptors increases insulin sensitivity and fatty acid oxidation, which results in a reduction of fat buildup in the liver and leads to a decrease in fibrosis and inflammation.
FXR is a nuclear receptor that regulates bile acid metabolism and signaling. Activation of the receptor inhibits bile acid synthesis from cholesterol via cytochrome P450 7A1 and increases bile acid conjugation, transport, and excretion. This protects the liver from the potentially harmful effects caused during bile acid accumulation. Tropifexor (Novartis/Pfizer) is a novel, highly potent, non-bile acid FXR agonist. It has demonstrated potent activity in rodent Parkinson’s disease models by measuring the induction of FXR target genes in tissues.
Selonsertib (Gilead) is a small molecule that inhibits apoptosis signal-regulating kinase 1 (ASK1). ASK1 has been shown to promote inflammation, apoptosis, and fibrosis in settings of oxidative stress. Non-alcoholic steatohepatitis (NASH) increases oxidative stress and ASK1 activation, so by inhibiting ASK1, selonsertib has been shown to decrease inflammation and fibrosis in patients with NASH.
Resmetirom (Madrigal Pharmaceuticals) is a thyroid hormone receptor (THR) β-selective agonist which selectively targets receptors in the liver. The THR is involved in the regulation of metabolism, cholesterol, and triglycerides, as well as the pathological buildup of fat in the liver. The high liver specificity of resmetirom aims to avoid adverse events associated with THR activation outside the liver.
Firsocostat (Gilead) is an acetyl-CoA carboxylase (ACC) allosteric inhibitor which binds to the biotin carboxylase domain of ACC with high potency and selectivity. Firsocostat inhibits both isoforms (ACC1 and ACC2) of ACC, which results in the reduction of the production of malonyl-CoA carboxylase, therefore reducing a key substrate for fatty acid synthesis. This also reduces the inhibitory effect of malonyl-CoA on the carnitine palmitoyltransferase 1 (CPT-1), which is the rate-limiting step in β-oxidation and leads to an increase in the breakdown of free fatty acids.
Emricasan (Conatus/Novartis) is a small molecule which inhibits pan-caspases. These enzymes are key modulators of apoptosis and inflammation, and chronically elevated apoptosis is often present in liver disease, which leads to the accumulation of apoptotic cells and the release of apoptotic bodies. These end products of apoptosis are engulfed by surrounding tissues which promote disease pathology and inflammation.
Dovato ([dolutegravir + lamivudine]; ViiV Healthcare) is a single-tablet regimen approved in the US for the treatment of HIV-1 infection in patients who are treatment-naïve. It is also being developed in the EU for the treatment of HIV-1 infection in patients who are treatment-naïve (with an approval decision expected by Q3 2019), as well as for patients who are virologically suppressed (US/Japan/EU).
Biktarvy ([bictegravir + emtricitabine + tenofovir alafenamide (TAF)]; Gilead) is an single-tablet regimen (STR) approved for the treatment of HIV-1 infection. It is a co-formulation of Gilead’s novel integrase strand transfer inhibitor (INSTI) bictegravir, and the marketed drug Descovy, which is a fixed-dose combination (FDC) of the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine and TAF.
Juluca ([dolutegravir + rilpivirine]; ViiV Healthcare/Johnson & Johnson) is a single-tablet regimen approved in the US for the treatment of patients infected with HIV-1 who have achieved viral suppression.
Odefsey ([rilpivirine + emtricitabine + tenofovir alafenamide (TAF)]; Gilead/Johnson & Johnson) is a single-tablet regimen approved in the US and five major EU markets (France, Germany, Italy, Spain, and the UK) for the treatment of HIV-1 infection. Odefsey contains Gilead’s nucleos(t)ide reverse transcriptase inhibitors (NRTIs) TAF and Emtriva (emtricitabine), and Johnson & Johnson’s non-nucleoside reverse transcriptase inhibitor Edurant (rilpivirine; Johnson & Johnson).
Symtuza ([darunavir + cobicistat + emtricitabine + tenofovir alafenamide (TAF)]; Johnson & Johnson) is a once-daily single-tablet regimen (STR) combination of the protease inhibitor (PI) Prezista, the two nucleos(t)ide reverse transcriptase inhibitors (NRTIs), Emtriva (emtricitabine; Gilead) and TAF (Gilead), and the boosting agent Tybost (cobicistat; Gilead). Symtuza is the first STR containing a PI.
Truvada ([emtricitabine + tenofovir disoproxil fumarate (TDF)]; Gilead/Japan Tobacco) is a once-daily, fixed-dose combination of two of Gilead’s marketed nucleoside reverse transcriptase inhibitors (NRTIs):
Cabotegravir is an integrase strand transfer inhibitor analog of Tivicay (dolutegravir; ViiV Healthcare), and rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), branded as Edurant (Johnson & Johnson).
Fostemsavir (GSK3684934) (ViiV Healthcare), previously known as BMS-663068, is an oral prodrug of GSK2616713 (formerly BMS-626529). It is an attachment inhibitor which binds to the gp120 protein of HIV to prevent viral attachment to the host CD4+ T cells, which is necessary for entry into host cells.
Leronlimab (CytoDyn) is a humanized monoclonal antibody directed against C-C chemokine receptor 5 (CCR5), which is a co-receptor required for the attachment and entry of CCR5-tropic HIV-1 viruses into host cells.
Complera (rilpivirine/emtricitabine/tenofovir disoproxil fumarate [TDF]; Gilead/Johnson & Johnson) is a single-tablet regimen for the treatment of HIV-1 infection.
Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate [TDF]; Gilead/Bristol-Myers Squibb) is a single-tablet regimen approved for the treatment of HIV-1 infection.
The Reyataz franchise comprises the standalone azapeptide protease inhibitor (PI) Reyataz (atazanavir; Bristol-Myers Squibb) and the fixed-dose combination of Reyataz and Tybost.
Isentress (raltegravir; Merck & Co) is a twice-daily, unboosted integrase inhibitor (INI) that is used in combination with other antiretroviral drugs for treatment of HIV-1 infection.
Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate [TAF]; Gilead) is a single-tablet regimen (STR) approved for the treatment of HIV-1 infection.
Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate [TDF]; Gilead/Japan Tobacco) is a single-tablet regimen for the treatment of HIV-1 infection. It is a co-formulation of marketed fixed-dose combination (FDC) Truvada, Vitekta, and Tybost.
The Prezista franchise comprises the standalone protease inhibitor (PI) Prezista (darunavir; Johnson & Johnson) and the fixed-dose combination of Prezista and Tybost (cobicistat; Gilead), which is branded as Prezcobix in the US and Rezolsta in the EU.
Triumeq ([dolutegravir + abacavir + lamivudine]; ViiV Healthcare) is a single-tablet regimen (STR) for the treatment of HIV-1 infection. It is a co-formulation of the marketed HIV drugs Tivicay (dolutegravir; ViiV Healthcare) and Epzicom ([abacavir + lamivudine]; ViiV Healthcare), which is known as Kivexa outside the US. Tivicay is an integrase inhibitor that blocks the insertion of the viral genome into the host genome, and Epzicom is a fixed-dose combination nucleoside reverse transcriptase inhibitor that prevents viral RNA replication.
Tivicay (dolutegravir; ViiV Healthcare) is a once-daily, unboosted integrase inhibitor (INI) for the treatment of HIV-1 infection.
Fetzima (levomilnacipran; Allergan) is a serotonin-norepinephrine reuptake inhibitor indicated for the treatment of major depressive disorder (MDD) in the US.
Travivo (gepirone ER; GlaxoSmithKline/Mission Pharmacal) is a pyridinyl piperazine 5-HT1A receptor agonist, and is distinct from available therapies as it is not a reuptake inhibitor and has no material norepinephrine or dopamine activity. Unlike tricyclic antidepressants or selective serotonin reuptake inhibitors that act on most or all of the 5-HT subtypes in the brain and may have several adverse effects, trials for Travivo have shown benign adverse effects without significant dopaminergic effects.
SAGE-217 (oral brexanolone; SAGE Therapeutics/Shionogi) is a novel, next-generation positive allosteric modulator that selectively binds synaptic and extrasynaptic gamma-aminobutyric acid-A (GABA-A) receptors and shares similar pharmacology properties to brexanolone.
Zulresso is SAGE Therapeutics’ proprietary intravenous formulation of brexanolone, which is an allosteric modulator of both synaptic and extra-synaptic GABA-A receptors.
Rexulti (brexpiprazole) is Otsuka’s latest atypical antipsychotic, approved simultaneously in the US for schizophrenia and major depressive disorder in July 2015. The drug acts similarly to Abilify (aripiprazole; Otsuka/Lundbeck), displaying partial agonism of dopamine receptors in the central nervous system.
Lexapro (escitalopram; Allergan/Lundbeck/Mitsubishi Tanabe/Mochida) is a selective serotonin reuptake inhibitor, and acts by blocking the re-uptake of serotonin.
Latuda (lurasidone; Sumitomo Dainippon/Angelini) contains the atypical antipsychotic lurasidone, which acts as an antagonist of dopamine receptors D2, and serotonin receptors 5-HT2A. By inhibiting the synaptic reuptake of dopamine and serotonin, Latuda helps to normalize brain activity and reduce schizophrenia symptoms.
Pristiq (desvenlafaxine; Pfizer) is purely a follow-on product to the former leading serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant Effexor (venlafaxine; Pfizer).
ALKS 5461 (Alkermes) is a fixed-dose combination of buprenorphine, a mu opioid receptor partial agonist and kappa opioid receptor antagonist, and samidorphan (ALKS 33), which is a proprietary opioid modulator.
Trintellix (vortioxetine; Lundbeck/Takeda) is the latest antidepressant to be approved in the US for major depressive disorder (MDD). The drug follows a successful line of antidepressants developed by Lundbeck, which includes Cipralex (escitalopram) and Cipramil (citalopram). Trintellix was first approved in the US in September 2013 and was made commercially available in January 2014, under the brand name Brintellix.
Eli Lilly’s Cymbalta (duloxetine), a serotonin-norepinephrine reuptake inhibitor, was initially approved in the US in August 2004 for the treatment of major depressive disorder. The company has since accrued a number of additional indications for Cymbalta, including diabetic peripheral neuropathic pain, generalized anxiety disorder, fibromyalgia in the US, and most recently, chronic musculoskeletal pain.
The Seroquel franchise contains quetiapine, which acts as an antagonist at multiple neurotransmitter receptors in the brain, such as serotonin 5-HT1A and 5-HT2, dopamine D1 and D2, histamine H1, and adrenergic alpha 1 and alpha 2 receptors.
Viibryd (vilazodone; Allergan) belongs to a new class of antidepressants, combining selective serotonin reuptake inhibitor activity with partial 5-HT1A receptor agonism, in order to produce its therapeutic effect.
Abilify (aripiprazole; Otsuka/Lundbeck) is an atypical antipsychotic that contains aripiprazole, a partial agonist of dopamine receptor D2 and serotonin receptor 5-HT1A, and antagonist of the 5-HT2A receptor.
Rapastinel is a synthetic tetrapeptide, comprising of threonine–proline–proline–threonine, that acts as a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor.
Fotivda (tivozanib; AVEO Oncology/EUSA Pharma/Kyowa Hakko Kirin) is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3. Inhibition of VEGF signaling in order to prevent angiogenesis is a well-established strategy across many tumor types; however, Fotivda’s potency, selectivity, and long half-life are hypothesized to improve the drug’s efficacy and safety in comparison to its predecessors.
Cancer cells are known to rely on glycolysis as an energy source. CB-839 (Calithera Biosciences) inhibits the glutaminase enzyme, reducing the ability of cancer cells to utilize glutamine in this biochemical pathway, thereby reducing cell proliferation and tumor growth.
Inlyta (axitinib; Pfizer) is a kinase inhibitor designed to selectively inhibit vascular endothelial growth factor receptor-1.
Bavencio (avelumab; Merck KGaA/Pfizer) is a fully human MAb targeting the PD-L1 protein.
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