Provided by GBI Research
Several notable innovative therapies spanning diverse indications and therapy areas have emerged in 2016. Some of the most promising of these, which have addressed unmet needs most significantly, are discussed below.
Epclusa for Hepatitis C
Hepatitis C has witnessed a treatment revolution in recent years, due to the emergence of direct-acting antiviral agents such as Olysio, Sovaldi, Harvoni and Zepatier. These therapies are associated with high rates of sustained virologic response – which is effectively considered a cure for hepatitis C – in over 95% of patients. They have also reduced treatment durations and enhanced safety and tolerability, particularly as many of these drugs can reduce or eliminate the need for interferon and ribavirin, previous standard-of-care therapies that are often associated with high toxicity.
Gilead has dominated the hepatitis C market in recent years thanks to the success of its blockbuster drugs Sovaldi and Harvoni, and its latest market addition Epclusa is also a potential game-changer. Epclusa combines the active pharmaceutical ingredients sofosbuvir and velpatasvir. Sofosbuvir inhibits the hepatitis C nonstructural protein 5B (NS5B), and is also used in Sovaldi and Harvoni. Velpatasvir, meanwhile, is a novel active pharmaceutical ingredient, and inhibits another hepatitis C protein, nonstructural protein 5A (NS5A). Both NS5B and NS5A play essential roles in the viral replication cycle, and are highly conserved across hepatitis C genotypes.
Targeting both proteins simultaneously has enabled Epclusa to demonstrate strong pan-genotypic efficacy. It is the first all-oral, fixed-dose, single-tablet combination regimen to be approved for the treatment of all six hepatitis C genotypes, which are classified as HCV1 to HCV6. Other direct-acting antivirals are only approved for specific genotypes – examples include Incivo (HCV1), Daklinza (HCV1 and HCV3), Olysio (HCV1 and HCV4), Sovaldi (HCV1 to HCV4), Harvoni (HCV1, HCV4, HCV5 and HCV6) and Zepatier (HCV1 and HCV4).
The approval of Epclusa therefore eliminates the need for genotype testing – a process that can create barriers to treatment access in resource-constrained settings. It is also the first single-tablet regimen approved for HCV2 and HCV3 patients that can be administered without ribavirin.
Targeted Therapies for Oncology
Venclexta is a first-in-class targeted therapy – a drug that is administered to a sub-group of a patient population based on specific molecular aberrations. It was recently approved for the treatment of patients with chronic lymphocytic leukemia whose tumors have a genetic aberration known as 17p deletion, and who have received at least one prior therapy. This chromosomal deletion, which leads to the loss of a tumor suppressor gene, is associated with poor prognosis, and treatment options are limited. The genetic marker has been identified in 3–10% of untreated patients, and 30–50% of relapsed and refractory cases.
Venclexta’s origins can be traced back to 1988, when researchers at the Walter and Eliza Hall Institute in Australia discovered that the B-cell lymphoma 2 (BCL2) protein promoted longevity of leukemia cells. The researchers hypothesized that reducing BCL2 activity may induce leukemia cell apoptosis, prompting a race to discover a drug capable of inhibiting this protein. The drug was eventually developed as a result of a collaboration between the Walter and Eliza Hall Institute, Abbott (subsequently AbbVie) and Genentech – although it took until 2011 for it to be investigated in clinical trials.
Encouraging results were observed from the outset, with Venclexta demonstrating unparalleled objective response rates in relapsed or refractory patients with 17p deletions. While this patient subgroup typically has a progression-free survival (PFS) duration of less than 12 months on chemotherapy, median PFS was not reached after a median follow up of 12 months in a Phase II trial.
Another promising first-in-class targeted therapy, which emerged this year, is Roche’s Tecentriq, which is indicated for the treatment of urothelial carcinoma – the most common type of bladder cancer. It is approved for use in patients with locally advanced or metastatic cancer who have received prior treatment with platinum-containing chemotherapy. Tecentriq’s launch has been eagerly anticipated, as unmet need within the metastatic cancer treatment setting was previously very high, with limited treatment options available. Prior to the approval of Tecentriq no second-line therapies had been approved in this treatment setting in the US, and only one had been approved in Europe, on the basis of a modest improvement in PFS.
Tecentriq utilizes a novel mechanism of action. It is an immunotherapy that disrupts signaling in the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway – a negative regulator of T-cell activity – by binding directly to PD-L1. This is thought to enable T-cell activation, stimulating an anti-tumor response. Opdivo and Keytruda, which were first approved for the treatment of melanoma in 2014, achieve PD-1/PD-L1 blockade by similar means, by targeting PD-1. However, Tecentriq is the first therapy to target PD-L1 directly.
Clinical data demonstrate that Tecentriq induces tumor responses across patient subsets. However, greater responses are observed in patients with the highest levels of PD-L1 expression. Consequently, a diagnostic test that detects PD-L1 protein expression was approved simultaneously, to help physicians determine which patients may benefit the most from treatment.
Furthermore, following on from Tecentriq’s approval in the second-line setting, Roche subsequently released data demonstrating that the drug significantly improved survival in the first-line setting, indicating that a label expansion into this setting is probable.
Nuplazid for Symptoms of Parkinson’s Disease
Another promising drug approval of 2016 is Nuplazid, the first drug indicated for the treatment of hallucinations and delusions associated with psychosis experienced by some Parkinson’s disease patients. These symptoms affect up to 50% of patients at some point during the course of their illness, and can be extremely disturbing, considerably impacting quality of life and resulting in loss of independence.
The approval of Nuplazid, which reduces the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease, therefore addresses a significant unmet treatment need. Discovered and developed by Acadia, Nuplazid represents a new class of drug – selective serotonin inverse agonists. It preferentially targets 5-hydroxytryptamine receptor 2A, which is thought to play important roles in Parkinson’s disease psychosis. Significantly, Nuplazid does not impair motor function, as it does not block dopamine receptors, or other receptors that are commonly targeted by other antipsychotic drug classes.
This year has seen the arrival of several innovative therapies designed to tackle infectious diseases such as Hepatitis C and disorders such as Parkinson’s disease. The above therapies have yielded impressive results and could greatly improve the lives of people affected by these diseases and conditions.
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