The Ministry of Health, Labour and Welfare in Japan has given full marketing authorisation to the oral selective inhibitor of PDE4 (phosphodiesterase) product from Celgene, known as OTEZLA. OTEZLA has been approved for marketing for providing treatment for plaque psoriasis in adult patients who have responded inadequately to topical therapies, as well as to adult patients who are suffering from psoriatic arthritis.
Psoriasis, of which plaque psoriasis is the most common form, is a chronic inflammatory skin disease. Psoriatic arthritis is a chronic and painful inflammatory disease resulting in swollen, tender and stiff joints, tendons and ligaments. The chairman and professor of the Department of Dermatology at Jichi Medical University, Mamitaro Ohtsuki, MD, PhD, says that the approval of OTEZLA is the first time such approval has been granted in Japan to an oral treatment for psoriasis in a quarter of a century. OTEZLA does not need to be monitored prior to administration, is easy to tolerate, and comes with a novel action mechanism.
OTEZLA is the first example of a whole new kind of medicines that have been given approval in order to treat the diseases known as psoriatic arthritis and psoriasis, both of which involve dysregulated activity in the immune system. Plaque psoriasis is a systemic inflammatory condition that affects around 430,000 people in Japan alone, and around 125 million people all over the world. It is characterized by the appearance of raised scaly skin lesions.
The approval given to OTEZLA by the Japanese government was based upon the safety and efficacy results from a Japanese phase 2b study, as well as two international phase studies – phase 2b and phase 3 – in adult patients suffering from psoriatic arthritis conditions. These ranged from moderate to severe. There were also three international phase 3 studies that were conducted in adult patients afflicted with psoriatic arthritis. Clinical studies found that the most common side effects of OTEZLA were nausea, headache, tension headache, upper respiratory tract infection and nausea.
According to the president of Celgene Inflammation and Immunology, Scott Smith, OTEZLA receiving approval in Japan represents another crucial milestone for the company, in its attempt to create innovative medicines that can address the needs of patients all over the world who have been suffering from chronic inflammatory diseases. Smith says that Celgene believes that the oral administration and novel mechanism of action with OTEZLA will offer patients suffering from psoriatic arthritis and plaque psoriasis in Japan a very welcome new option.
As of December 2016 OTEZLA has now been given approval in 37 countries, including parts of Europe and the United States.
Details of OTEZLA
OTEZLA is a small-molecule phosphodiesterase 4 inhibitor that can be taken orally, and is specific to cyclic adenosine monophosphate. The inhibition of phosphodiesterase 4 causes an increase in intracellular cAMP levels that are believed to be responsible for indirectly modulating inflammatory mediators production. The specific way in which the therapeutic action of OTEZLA is exerted in psoriatic arthritis and psoriasis patients has not been well defined.
Warnings, precautions and safety information
OTEZLA is contraindicated in patients who have a known apremilast hypersensitivity, as well as hypersensitivity to any of the other excipients found in the formulation. The benefits and risks of OTEZLA treatments on patients suffering from suicidal thoughts or depression, or who begin to suffer them while on the treatments, need to be carefully weighed. Barely 1 percent of patients on OTEZLA suffered from any form of depression during the period they were taking the medication. It is also a good idea to regularly monitor body weight, and to consider discontinuing the use of OTEZLA in the event of clinically significant or unexplained weight loss.
Less than five percent of psoriasis patients also reported adverse reactions to OTEZLA, ranging from diarrhoea to nausea, headache, tension headache and upper respiratory tract infection. The same reactions were also experienced by less than 2 percent of psoriatic arthritis patients on the medication. The effect of OTEZLA on pregnant women has not been studied, and it should therefore not be used during pregnancy – unless the potential benefit is justified in comparison to the potential risk for the foetus. Caution is also advised for nursing women using OTEZLA. Patients suffering from renal impairment should have their dosage of OTEZLA reduced.