A first-in-class drug has a new mechanism of action, and excitement for an absolutely new type of therapy is palpable, with the promise of leveraging biotechnology to heal more people in mind. But, do first-in-class drugs perform better than other new drugs?
According to results from one study comparing 292 drugs approved between 1997 and 2012, the benefit-to-harm ratio (ie, post-market safety warning/withdrawals) of first-in-class drugs does, indeed, exceed other drugs.
With the hope that new therapeutics bring, here are five new drug classes you should know about.
Protein epitope mimetic molecules
Pseudomonas aeruginosa is a highly resistant, opportunistic bacterium and the leading cause of morbidity and death in those with cystic fibrosis.
Representing a new class of antibiotic that fights P. aeruginosa, protein epitope mimetic (PEM) molecules like POL7001 slow the transport of lipopolysaccharides to the bacterial outer membrane. In preclinical models, this drug decreased bacterial burden and inflammation during both short- and long-term infection. Furthermore, multidrug-resistant isolates taken from patients with cystic fibrosis were sensitive to POL7001.
“New treatment options are urgently needed to fight resistant pathogens, especially resistant Pseudomonas strains,” said Daniel Obrecht, chief scientific officer of Polyphor, the company that developed the POL7001 compound.
According to the authors of a review article published in Biotechnology Advances: “The new mode of action, the efficient pulmonary delivery and the potent in vitro and in vivo activity suggest POL7001 as a novel therapeutic agent for future clinical trials. The side effects of POL7001 have not been reported yet.”
Exportin 1 inhibitors
Selinexor is a first-in-class exportin 1 (EXO1) inhibitor that, when combined with dexamethasone, is used as last-line treatment of relapsed refractory multiple myeloma (RRMM), also referred to as triple-class refractory multiple myeloma. To be eligible for this drug, patients must have received three prior therapies and been refractory to at least one proteasome inhibitor, an anti-CD38 monoclonal antibody, and an immunomodulatory imide drug.
Selinexor works by selectively inhibiting XPO1 in a slowly reversible manner to induce tumor cell apoptosis and reactivate tumor suppressor proteins. When combined with dexamethasone in RRMM treatment, the median duration of response is 4.4 months.
Selective non-prostanoid IP prostacyclin receptor agonists
Selexipag is a first-in-class drug that was approved by the FDA in December 2015 for the treatment of pulmonary arterial hypertension (PAH), which carries a poor prognosis. This drug works to delay disease progression and decrease hospitalization rates in those with PAH. It belongs to a class of drugs called selective non-prostanoid IP prostacyclin receptor agonists.
Selexipag’s active metabolite is ACT-333679 (MRE-269), a prostacyclin receptor agonist, which effectively increases vasodilation and decreases elevated pressure in lung blood vessels.
Selective sphingosine-1-phosphate receptor modulators
Since the introduction of fingolimod, several other selective sphingosine-1-phosphate receptor modulators for the treatment of multiple sclerosis (MS) have entered the pipeline. This class offers benefits of decreased MS relapses, MRI lesions, and disability progression, with rare adverse effects. Although new, these drugs are hypothesized to offer longer-term benefits in those with MS.
Sphingosine-1-phosphate is a bioactive phospholipid that is involved in a range of molecular processes, including angiogenesis, calcium metabolism, cell differentiation, cell migration/survival, endothelium integrity, heart rate, immunity, inflammation, angiogenesis, and survival. Actions of these drugs are mediated by the G-protein-coupled receptor subtypes S1P1–5.
Serotonin modulators like vortioxetine and vilazodone represent a new class of drug. They have several molecular mechanisms of action in addition to serotonin transporter inhibition. For instance, vortioxetine is thought to inhibit transmitter reuptake and block interactions that happen at different 5-HT receptor sites.
In those with treatment-refractory depression, vortioxetine is being examined as a potential alternative to selective serotonin reuptake inhibitors as well as serotonin and noradrenaline reuptake inhibitors. It not only has antidepressant effects, but also boosts cognitive function in those with depression.