Interferon beta-1b (Betaferon) is the world's first treatment able to demonstrate a therapeutic effect in both relapsing-remitting and secondary progressive MS. It is also the first and only interferon to be licensed in both these indications.
Interferon beta-1b is a highly purified, genetically engineered protein. It is produced by bacterial fermentasyon in a strain of E.coli bearing a plasmid engineered to include a modified gene for human interferon beta.
Interferon beta-1b was clinically developed by Schering AG following the acquisition to the rights of the molecule from a US biotechnology company in the late 1980s.
Interferons are known to possess effective antiviral and antitumour properties, and so the molecule was potentially of interest for several viral diseases. At that time the genetically engineered molecule was thought to have potential for the treatment of cancer and multiple sclerosis.
The product was tested successfully in multiple sclerosis by Schering's US subsidiary Berlex Laboratories. In 1992, a US product licence application was made for permission to promote use of the product, named Betaseron in the US, in ambulant patients with relapsing-remitting MS.
In February 1993, the results of a large multicentre trial involving 372 patients with relapsing-remitting MS were published. These results showed that in patients with relapsing-remitting MS, Betaseron reduced the expected number of relapses by one third, reduced the duration of relapses which did occur and reduced the number of MS lesions seen in the brains of patients on MRI.2
For the first time a treatment was shown to have been capable of affecting the pathogenesis of MS. Marketing approval in the US was granted in June 1993 and the treatment was launched in October of that year. In Europe, a licence application was filed in May 1994 and the product was launched there for the treatment of relapsing-remitting MS in December 1995. Since then about 85,000 patients have been treated world-wide.
Research subsequently began to evaluate the role of Betaferon in patients with the more severe secondary progressive form of MS for which there was no treatment. A clinical study began in 1994 in 32 European centres in which 718 patients were randomised to receive either Betaferon or placebo. The study's primary endpoint was time to confirmed disease progression, defined as a sustained increase on the Expanded Disability Status Scale (EDSS) of one point or of 0.5 points in patients with an initial EDSS score of 5.5 or higher at study entry.
In February 1998, the European comparative trial ended following a planned interim analysis conducted by the study's independent advisory board, which recommended that all patients in the placebo group be switched to active drug.
In June 1998, Schering presented the study results to an audience of neurologists at the European Neurology Society's annual meeting in Nice. It showed a highly statistically significant benefit favouring patients on Betaferon. Even within this brief study period, Betaferon demonstrated it could delay the progression of disability by nine to twelve months and keep patients out of a wheelchair for up to one year. The study was published in November 1998.3
In May 1998, an application was made to the European health authorities and in June to US health authorities for approval to promote use of Betaferon in secondary progressive MS. That application was granted in Europe in January 1999 which means that European MS patients with either the relapsing-remitting or secondary progressive forms of the disease can now be treated with an effective therapy that will slow the rate of neurological deterioration and preserve mobility for a longer time.
Since most individuals with relapsing-remitting MS go on to develop the secondary progressive form of the disease, they can now continue on Betaferon throughout.
Specialists now advocate that patients start on disease-modifying therapy of proven efficacy as early as possible after diagnosis. This maximises the opportunity to delay the disease process before irreparable damage has been caused to the myelin sheaths and axons of nerves resulting in permanent disability.