The Ministry of Health has given the green light to the approval and funding of PONVORY (ponesimod), a drug Janssen Pharmaceutical Companies of Johnson & Johnson for the treatment of adult patients with relapsing forms of multiple sclerosis (MS), which are the most common, with active disease defined by clinical features or imaging studies.
Ponesimod is an oral therapy -administered once a day- approved by the data collected in the OPTIMUM phase 3 trial, a multicenter, randomized, double-blind, active-control, parallel-group superiority study involving 1,133 adult patients (aged 18-55) from 28 countries1, including Spain. The trial was designed to assess the efficacy and safety of once-daily oral ponesimod (20 mg) compared to once-daily teriflunomide (14 mg), a widely used first-line oral treatment in patients adults with MRD1.
As pointed out by the Doctor Xavier Montalbán, Head of the Neurology Service at the Vall d’Hebrón University Hospital in Barcelona and Director of the CSUR Multiple Sclerosis Center of Catalonia (CEMCAT), “This study was the first to compare two oral treatments in multiple sclerosis, which is very relevant. The results showed that ponesimod had significantly greater efficacy, reducing the annual relapse rate by more than 30% and a 56% decrease in the number of new active lesions detected by MRI.
This specialist also highlighted the superior effect of the new drug approved in Spain on the degree of cerebral atrophy, with a significant reduction in single active lesions combined (LAUC), as observed in brain MRI. “All this indicates that its anti-inflammatory effect is very powerful, in addition to its positive effect on brain activity. In other words, all parameters that indicate a reduction in inflammation are favorable to ponensimod.
For his part, the Dr. José Miguel Láinez, President of Spanish Society of Neurology (SEN) there Head of the Neurology Service of the Clinical Hospital of Valenciapointed out that “this therapy allows early treatment with a very effective drug, orally, avoiding the patient’s visit to the hospital and with an excellent tolerance profile”.
Regarding its pharmacokinetics, ponensimod has a rapid reversibility of its pharmacological effect, returning lymphocyte counts to normal levels within seven days of stopping treatment. This means that levels of lymphocytes, the body’s defense cells, return to normal when treatment is stopped. “In just seven days, this therapy achieves this reversibility. Something that is not common with other selective modulators, with which we find patients with sustained lymphopenia that prevent us from starting other treatments, if necessary. [por ejemplo, en caso de que el paciente presente una infección o desee planificar un embarazo]. In addition, in most cases, it is not necessary to admit the patient to receive the first dose and to monitor him by electrocardiography. In fact, it is a drug that has shown a very remarkable efficacy and safety profile,” Dr. Montalbán points out.
The invisible symptoms
MS is a disease whose symptoms vary from person to person and which also requires dealing with so-called “invisible” symptoms such as pain, fatigue, sexual problems, urinary problems and mental confusion. Symptoms difficult to treat and very debilitating for people diagnosed with this disease.
In this sense, the Dr. Celia Oreja-Guevara, Head of the CSUR Section for Multiple Sclerosis, Neurology, at the San Carlos Clinical Hospital in Madrid, commented that “we do not have objective tools to be able to measure these symptoms, beyond the perception of patients. Fatigue, for example, is a big problem for these people, which on many occasions even forces them to stop working. It also generates shame as their environment can often think it is something fake.
The OPTIMUM study showed the superiority of ponesimod in stabilizing fatigue symptoms over 2 years, assessed by the FSIQ-RMS questionnaire, developed specifically for relapsing multiple sclerosis. In this sense, Dr. Montalbán pointed out that this effect is another peculiarity that differentiates Ponesimod from the others available: “something very relevant, given that fatigue is so frequent and disabling in these people”.
The average in the diagnosis of MS is one to six months from the appearance of the first symptoms. In this context, Dr. Oreja-Guevara clarified that “in the face of a symptom of blurred vision, if the patient goes to the emergency room, he is usually diagnosed immediately. But if the patient has numbness or tingling, they are more likely to be referred to an orthopedic surgeon before reaching a neurologist. This is why there is so much jet lag in establishing a diagnosis, because the type of symptom a person presents greatly influences”.
process as soon as possible
Since the appearance of the first treatment for this disease in 1995, the advances made in the field of multiple sclerosis have been very significant. During all this time, in addition to therapeutic advances, other aspects have been confirmed, such as the importance of treating as early as possible and with highly effective therapy in the first years after diagnosis, when it is still possible to modify the future course. of the disease. “As is the case with strokes,” Dr. Oreja-Guevara pointed out, “in multiple sclerosis, time is the brain. The earlier you treat, the better the course of the disease. The goal is to prevent the patient from accumulating sequelae and lesions in the brain, thereby reducing disability and associated relapses.”
In this context, Dr. Láinez added that in recent years it has been shown that the early use of highly effective treatments is associated with a better medium and long-term prognosis in terms of disability. “We are seeing an improvement in the functional status of patients for longer periods of time,” he commented.
For the president of the SEN, research in neuroscience has a fundamental stake, which is to obtain ethological treatments for neurodegenerative diseases, knowing that they can become the epidemic of the 21st century. “If we are talking about multiple sclerosis -he continues-, one of the most immediate challenges is to use the new biomarkers in routine clinical practice to be able to better select the most effective therapies from the start of disease”.
As concluded by Dr. Henar Hevia, Janssen Medical Director, “This approval underscores our company’s commitment to seek to reduce the burden, disability and significant personal and societal impact of multiple sclerosis, for which there remains a significant unmet medical need. This authorization in our country also ratifies Janssen’s continued commitment to neuroscience, a field in which we have worked since 1958 and in which we will continue to focus our efforts day after day.”