Oral Multiple Sclerosis drug, Cladribine, appears effective, but cancer cases raise concerns
Merck KGaA reported late-stage data showing that its cladribine tablets significantly cut the rate of clinical relapses, disability progression and brain lesions in patients suffering from relapsing remitting multiple sclerosis, echoing preliminary data reported earlier this year.
But a handful of cancer cases in the study may raise some safety concerns for physicians that must choose cladribine over alternative therapies that have longer safety data in larger patient populations.
Merck, based in Germany, is currently leading the race to bring an oral therapy to patients with the debilitating disease and plans to use the data to file for regulatory approval in Europe and the U.S. in mid-2009. Currently, the leading MS therapies sold by Biogen Idec Inc. are once-daily injections.
"When you have the possibility to be first, you have the possibility to shape the market," said Elmar Schnee, head of Merck's pharmaceuticals business and member of its executive board, in an interview.
In January, Merck reported that the company-run trial, involving 1,326 patients and lasting two years, met its primary goal of reducing the annualized relapse rate in comparison to placebo, cutting that rate by between 55% and 58% depending on the dosage.
The full data, presented at the American Academy of Neurology meeting in Seattle, show that the relative relapse risk in cladribine was about half of that seen in patients on placebo.
Over two years, 80% of the patients in the low-dose group and 79% of those in the high-dose group experienced no clinical relapse, compared to 61% of those on placebo.
In another secondary goal of the trial, cladribine treatment cut the risk of disability progression by more than 30%. Both doses also reduced different types of brain lesions in MS patients, according to the study.
Notably, four patients in the cladribine group developed cancer during the study and another case emerged six months after the study ended. One of the patients eventually died.
There were no occurrences of cancer in the placebo arm.
The cancers were "isolated cases" in different organ systems, Merck said, and expects that ongoing studies may shed more light on the issue.
"I think this will help in trying to understand if there is, or there is not, a relationship between cladribine and the occurrence of malignancies," said Bruno Musch, head of global clinical development for neurodegenerative diseases at Merck.
"So far, there is no element to conclude that there is a relationship," he said.
Lymphopenia, a decrease in a type of white blood cells called lymphocytes, occurred more frequently in the cladribine groups - 22% of patients in the low dose and 31% in the high dose. The development was expected because the drug disrupts certain white blood cells that are thought to play a role in MS.
No related increase in patient infections was reported in the study.
Helen Yates, Chief Executive of the Multiple Sclerosis Resource Centre (MSRC) said,:
"It is very encouraging news that Cladribine seems to not only reduce relapse rate but also seems to have a positive impact on disability progression. However we would like to see the issues and concerns about the potential carcinogenic factors addressed as soon as possible so that people affected by MS can consider this treatment without the concern of cancer causing agents. Nevertheless, any oral therapy that demonstrates efficacy is very welcome as injectable therapies cause concerns and discomfort for so many"
Merck expects that it can gain approval for cladribine using only the one Phase III study, and has spoken with European and U.S. regulators about the issue.
Cladribine is taken very infrequently when compared to many MS drugs that are taken daily. In the study, patients were given two or four treatment courses in the first year, with each course being a daily pill for four to five consecutive days. In the second year, two treatment courses were administered to all patient groups.
Despite its infrequent dosing and being a pill, rather than a biologic, Merck will likely be aggressive in pricing the drug.
"I think that pricing has to be in line with the benefits that the drug brings to the patient," Schnee said. "It doesn't differ if you have an injectable or if you have a tablet."
Biogen's Avonex, the MS market leader, is currently sold for about $30,000 a year.
Although Merck is aiming to be the first oral therapy, Novartis AG is hot on its heels.
Earlier Wednesday, the Swiss drug giant said data on its own MS pill, FTY720, showed that 80% to 83% of patients remained free of relapses during the one-year study - compared to 69% of those who took Avonex.
Novartis also disclosed a patient death, highlighting concerns about the drug's safety profile. The company plans to file for regulatory approval in Europe and the U.S. at the end of 2009.
Biogen, which has a product portfolio focused on MS, is developing BG-12, an oral drug in late-stage trials with data likely in 2011.
Source: Marketwatch © 2009 MarketWatch, Inc (30/04/09)
Treatment: CCSVI both IJV ballooned 09/2010, No DMDs, Tysabri on hold after 24 Infusions, after LDN, ABX Wheldon Regime for 1 year.