Added benefit of colestilan is not proven

Colestilan (trade name: BindRen) has been approved in Germany since January 2013 for the treatment of patients with chronic renal failure who receive haemodialysis or peritoneal dialysis. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the current standard therapy. Patients for whom calcium- and aluminium-based phosphate binders are not an option have lesser benefit from colestilan than from sevelamer hydrochloride: In the key study, they discontinued treatment more frequently because of side effects. An added benefit is not proven in patients without this contraindication because the drug manufacturer did not present any relevant studies.

G-BA specified appropriate comparator therapy

If the kidney can no longer regulate the salt, water and acid-base balance, phosphate, among other substances, accumulates in the blood (hyperphosphataemia). Phosphate binders aim to help bind the phosphate ingested with the food and reduce complications such as cardiovascular disease.

The Federal Joint Committee (G-BA) distinguished between two subindications and specified different appropriate comparator therapies for them: In patients for whom calcium- and aluminium-based phosphate binders are not an option, e.g. because of hypercalcaemia, colestilan is to be compared with sevelamer or lanthanum carbonate. If there is no contraindication, calcium- or aluminium-based phosphate binders are the comparator therapy.

No relevant study for one subindication

An added benefit of colestilan is not proven in patients for whom calcium- or aluminium-based phosphate binders – alone or in combination – are generally an option. The manufacturer did not present a relevant study for this comparison.

Only one quarter of the study participants corresponds to the target population

For the second subindication, there was a randomized controlled trial, which tested colestilan versus sevelamer hydrochloride. However, most participants did not have a contraindication to calcium- or aluminium-based phosphate binders, so that eventually only just under one quarter (24.5%) could be used for the benefit assessment. The Institute also considered the results for the total study population to be able to interpret the results of this comparatively small target population of 81 patients better.

The study duration was only 12 weeks, which is very short, considering that this is a long-term treatment.

Often no results or no group differences

There were no results for several outcomes because the corresponding events did not occur at all in the target population and only rarely in the study population within the 12 weeks during which the patients were treated in the study. This was the case for mortality (all-cause mortality), symptomatic vertebral and non-vertebral fractures, as well as gastrointestinal disorders and metabolic acidosis.

There were no statistically significant differences between the colestilan arm and the sevelamer hydrochloride arm regarding cardiovascular events (diseases of the heart, the vessels and the nervous system) and severe side effects (serious adverse events).

The study did not record data on health-related quality of life.

Treatment discontinuation more frequent under colestilan

The situation was different for the outcome "treatment discontinuation because of side effects": This was more frequent under colestilan than under sevelamer hydrochloride. The difference was statistically significant in the study population, and the result, which was below the significance threshold, was similar in the target population. Overall, there is a hint of greater harm from colestilan. Due to the uncertainty of data its extent is non-quantifiable.

Because there is only this negative, but no positive effect, the Institute overall assumes a hint of a lesser benefit of colestilan in comparison with sevelamer hydrochloride. This applies to patients with contraindication to calcium- and aluminium-based phosphate binders. The added benefit of colestilan is not proven for patients without contraindication.

G-BA decides on the extent of added benefit

The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer’s dossier and IQWiG’s assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.

An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website gesundheitsinformation.de, published by IQWiG, provides easily understandable and brief German-language information on colestilan.

The G-BAwebsite contains both general English-language information on benefit assessments pursuant to §35a Social Code Book V and specific German-language information on the assessment of colestilan.

More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on .informedhealthonline.org). If you would like to be informed when these documents are available, please send an e-mail to info@iqwig.de.