Date: 2012-02-14
Type of information: Halting of the trial
phase: 3
Announcement:
Company: Karo Bio (Sweden)
Product: eprotirome
Action mechanism:
Disease: heterozygous familial hypercholesterolemia (HeFH)
Therapeutic area: Cardiovascular diseases - Genetic diseases - Rare diseases
Country: mostly in Europe
Trial
details: The study will be conducted at 70 clinics in 12 countries, mostly in Europe. The relatively large number of clinics is required to recruit enough patients during a limited period of time. The study will involve a total of 630 patients with the hereditary condition Heterozygous Familial Hypercholesterolemia (HeFH) who will be treated with eprotirome for two years.
Latest
news: * On February 14, 2012, Karo Bio has decided to discontinue the development program for eprotirome after an animal study has demonstrated unwanted effects following long-term exposure. The planned spin-off of the preclinical part of operations will not proceed. The animal study is a toxicology study in which damage to cartilage was seen in dogs that were given eprotirome for up to 12 months. The cartilage damage was apparent only after 12 months exposure and occurred in all animals treated with high doses but was also seen in the lower dose groups. The control animals displayed no damage.
These unexpected findings mean that it cannot be excluded that also humans may suffer from similar cartilage damage. Chronic treatment with eprotirome must therefore be considered as too risky in relation to the lipid-lowering effect that the current study intends to demonstrate.
Eprotirome’s steering committee decided to recommend Karo Bio to terminate the ongoing phase III study. The findings also mean that the regulatory prerequisites to continue the study as planned are not in place.
In a six-month toxicology study in dogs these findings were not observed and patients included in the phase III study have been given eprotirome during a considerable shorter period of time.
The total cost of eprotirome’s phase III program that was scheduled to run until 2014, has previously been estimated to approximately SEK 300 million. The cost of the program through 2011 totalled approximately SEK 100 million. Karo Bio will take wind-up charges in the first quarter of 2012 totalling approximately SEK 55 million. This includes costs for terminating the phase III program, and all wind-up costs. It is the company’s assessment that financing of the operations is secured for at least 12 months from today.
Karo Bio has previously announced a streamlining of operations with the sale of the preclinical operations, which would result in two companies: one focused on eprotirome and the other organized around Karo Bio’s unique knowledge in nuclear receptors. The preclinical part was intended to be sold to new owners and strengthen Karo Bio’s financial position. The decision to terminate the eprotirome program changes the motives for such a transaction. The Board will therefore halt preparations to split the company and focus operations on the preclinical projects
In preclinical operations, Karo Bio has several development programs built on its knowledge of drug development based on nuclear receptors. For one of these programs (RORgamma) a collaboration and licensing agreement was signed with Pfizer in December 2011, which during the first two years will provide Karo Bio USD 10-14 million and during long time potential revenue of up to USD 217 million, and furthermore royalty revenue. Karo Bio is also engaged in project development in the areas of the receptors ERbeta and GR. Commercial discussions are ongoing regarding ERbeta.
* On November 2, 2011, a total of 630 patients with Heterozygous Familial Hypercholesterolemia (HeFH) will be included in the study. The purpose of the study is to determine safety and efficacy of eprotirome in long-term treatment of HeFH patients. The main study parameter of efficacy is reduction of LDL-cholesterol in the blood. Karo Bio’s study is led by Professor John J.P. Kastelein at Amsterdam Medical Center. An interim analysis, which will assess preliminary efficacy of eprotirome, is planned for during the second quarter of 2012. This analysis, together with the ongoing monitoring of safety data, will provide further information regarding both safety and efficacy of eprotirome.
Karo Bio's goal is to complete the study so that a registration application may be submitted in the EU during 2014.The first patient has now been included in Karo Bio's phase III trial (the AKKA study) with eprotirome. A total of 630 patients with the hereditary condition HeFH will be studied for safety, and to confirm the beneficial effects on LDL-cholesterol that has been shown previously.
* On September 17, 2011, Karo Bio AB has received approval from national regulatory authorities to start its phase III patient study with eprotirome, enabling the study to start as planned with an Investigators meeting in September. The official start of the study takes place on September 22, when investigators from all participating clinics, gather for an investigators meeting that primarily will address the practical management of the study. Karo Bio’s goal is to complete the study so that a registration application can be submitted in the EU in 2014.
