Nitec Pharma AG, a specialist pharmaceutical company focused on the treatment of chronic inflammatory diseases, announced positive results in a phase III clinical trial with Lodotra, a new, modified-release tablet that has been developed to optimize the efficacy of orally administered low-dose prednisone in Rheumatoid Arthritis (RA).

Lodotra provides all the benefits of standard immediate release (IR) prednisone but has the additional, clinically important advantage of reduced morning stiffness combined with a convenient dosing regimen and a comparable safety profile, a Nitec Pharma release stated.

The diurnal rhythm in RA is characterised by elevated night time levels of inflammatory cytokines such as IL6, which leads to extreme stiffness and pain in the hours immediately after awaking. It has been established that these morning symptoms can be addressed with prednisone administered at 2am. However, until now this has been impossible without disturbing sleep. Lodotra is an oral medication that has a unique delivery system that ensures rapid release of the prednisone from the tablet core about 4 hours after ingestion. Administration of Lodotra at night time (10 PM) results in release of prednisone at about 2am for a more effective treatment of the morning symptoms of RA.

The trial involved 288 patients in 26 centres in Europe, and was a randomized, double-blind, active-controlled, parallel-group Phase III study. The study compared the efficacy and safety of Lodotra given to patients before sleep the evening before, with standard immediate-release (IR) prednisone (following the current recommended regimen where prednisone is administered in the morning at 8am) over a period of 12 weeks. The duration of morning stiffness (the primary clinical endpoint of the study) was significantly reduced in the Lodotra group while under standard IR prednisone no change in morning stiffness was shown. In half the patients a reduction of more than one hour or one third was observed and those patients also showed a reduction in pain of one third. Lodotra was also shown to be well tolerated and just as safe as the standard regimen. Importantly, IL6 levels were shown to be reduced in the Lodotra group but remained constant in the standard prednisone group indicating that this reformulation of prednisone was exerting a specific inhibitory action on what is thought to be a key biological marker of the inflammatory process in RA.

Prof. Frank Buttgereit, Charite Berlin; principal investigator in the study commented: "These results confirm the hypothesis that the adaption of the timing of oral glucocorticoids to the circadian rhythms in RA could lead to a more effective therapy without increasing the dose of prednisone. The benefit of Lodotra results in a clinically relevant reduction of morning stiffness added to all known therapeutic effects of IR prednisone. The new administration mode is also convenient for the patient and was well tolerated."

"The results of the study confirm our expectations of being able to provide a steroid treatment that directly addresses the problems of morning symptoms in rheumatoid arthritis by administration of prednisone at a physiologically appropriate time" stated Dr. Achim Schäffler, co-founder and Head of R&D at Nitec Pharma. "Lodotra has been shown to address debilitating and painful morning stiffness and should directly improve the lives of people with RA. Our product can also be applied to other indications such as Polymyalgia Rheumatica (PMR) and asthma, which we plan to address next."

"We are delighted to have such positive results in a Phase III trial and have already submitted a dossier for marketing authorisation in Europe in August. We also plan to seek marketing authorisation for North America and the Far East," commented Jochen Mattis, co-founder and Head of Marketing and Sales at Nitec Pharma, "We will also be seeking marketing partners to realise the commercial value of Lodotra worldwide, in addition to the agreement we already have with Merck KGaA in Germany and Austria."