Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Oct 2020
ReviewMelflufen for relapsed and refractory multiple myeloma.
The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of standard-of-care agents such as immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies are increasingly used in earlier lines of therapy. Patients with disease that is refractory to multiple novel agents represent a population with high unmet medical need and for whom therapies with new mechanisms of action could be beneficial. Melphalan flufenamide (melflufen) has demonstrated encouraging activity in patients with relapsed and refractory multiple myeloma. ⋯ Melflufen has potential to fill a gap in the myeloma treatment landscape by providing a new mechanism of action with clinically meaningful efficacy and a favorable safety profile in patients refractory to multiple novel agents.
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Expert Opin Investig Drugs · Oct 2020
ReviewBaricitinib: therapeutic potential for moderate to severe atopic dermatitis.
Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by multiple signals including janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Current therapeutic armamentarium consists of a limited number of drugs which may result in the insufficient management of AD. Preclinical evidence regarding inhibition of JAK/STAT led to the development of a promising class of therapeutics, namely, JAK inhibitors. Baricitinib, a novel JAK1/JAK2 inhibitor is currently under investigation in AD clinical trials. ⋯ Baricitinib showed promising preliminary data in terms of efficacy in phase II and III trials, with a very rapid onset of response and great improvements of itch and sleep disturbances. These aforementioned aspects combined with the advantage of an oral formulation have reduced drug production costs compared to biologic agents and could lead to consideration of baricitinib as a first line systemic treatment. Also, in some countries, it could be a therapeutic option in the case of contraindication or failure of conventional systemic drugs prior to biologic therapies. Data related to long-term safety and efficacy will be important to refine the place-in-therapy of this drug.
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Expert Opin Investig Drugs · Aug 2020
ReviewPamrevlumab for the treatment of idiopathic pulmonary fibrosis.
The two available therapies for idiopathic pulmonary fibrosis (IPF), pirfenidone and nintedanib, slow down but do not halt IPF progression. As such, in the last few years several agents with specific molecular targets have been investigated to find a cure forIPF. Pamrevlumab, a recombinant human antibody that binds to connective tissue growth factor (CTGF) has emerged as a potential therapy for IPF and has advanced to phase 3 clinical trials. ⋯ Pamrevlumab was effective and safe in patients in a placebo-controlled phase 2 trial, demonstrating its potential to become an alternative therapeutic option for IPF; however, the feasibility of intravenous administration in clinical practice may be a hurdle to its use as a first-line treatment. Further studies are necessary to assess its effects when administered with pirfenidone or nintedanib and this could open up a new era of combined therapeutic approaches for IPF.
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Lopinavir in combination with ritonavir is approved for the treatment of HIV and has recently been subject to a clinical trial in severe COVID-19. ⋯ In my opinion, the rationale for undertaking a trial of lopinavir/ritonavir in COVID-19 was poor. The analysis of a modified intention to treat group analysis in LOTUS China may have introduced bias. After LOTUS China, there is probably no future for lopinavir in the treatment of severe COVID-19, but some clinical trials for prevention or in various stages of COVID-19 have recently started or are ongoing. The major limitation of these trials is that as lopinavir does not inhibit COVID-19, it is unlikely to prevent infection, reduce viral load, or reduce the severity. However, these trials may be worthwhile in finally determining whether lopinavir has any role in preventing or treating COVID-19.
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Expert Opin Investig Drugs · Aug 2020
Review Comparative StudyBempedoic acid, an inhibitor of ATP citrate lyase for the treatment of hypercholesterolemia: early indications and potential.
The lowering of low-density lipoprotein cholesterol (LDL-C), regardless of the method used, results in a reduction of cardiovascular events. Bempedoic acid is a new and until now, the only approved adenosine triphosphate citrate lyase inhibitor that works through the cholesterol-synthesis pathway (similar to statins) that leads to a safe and effective reduction in LDL-C. ⋯ In the United States, bempedoic acid is currently approved for use in secondary prevention. In primary prevention, its approval is limited to individuals with heterozygous familial hypercholesterolemia (FH). However, its tolerability and safety profile may warrant its use in primary prevention besides FH. Even though its efficacy appears weaker than high-intensity statins, it may be a useful adjunct in individuals who achieve less than desirable LDL-C reductions with statins or who cannot tolerate statins, where bempedoic acid alone or in combination with ezetimibe may be useful alternatives.