This article is provided to FT.com readers by Pharmawire—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.pharmawire.com
--------------------------------------------------------------------------------------------------------
Celgene’s attempt to gain European approval for Revlimid based on a single-arm clinical study is a risky move and should be studied in active-controlled clinical trials, physicians interviewed by Pharmawire said.
They noted that the European Medicines Agency (EMEA) prefers that new drugs for conditions where available treatments already exist be tested in an active-controlled study. The study drug can be checked against the current standard of care to make sure it is on par. The physicians also said the EMEA encourages the testing for both medical and ethical reasons.
In the US the FDA approved in September 2005 Lenalidomide Celgene Europe (the name of Revlimid indicated for MDS) for the treatment of patients with transfusion-dependent anemia associated with low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality.
Michael Kosorok, director of biostatistics at the University of North Carolina in Chapel Hill said that single-arm studies are not enough to measure a drug’s efficacy. Revlimid’s use in the treatment of patients with MDS should be confirmed by studies where the drug has been compared to treatments already approved for the indication.
Kosorok added that the results of Revlimid’s single-arm study that Celgene submitted for regulatory approval cannot be compared to other studies. Only studies comparing these drugs head-to-head could determine whether one is more effective than the other. The nuances of individual clinical trials such as study duration, patient population (treatment naïve or treatment resistant patients) and wash-out periods makes it impossible to compare Revlimid’s efficacy to other treatments for MDS (such as MGI’s Dacogen, Pharmion’s Vidaza, erythropoietin stimulating agents and growth factors).
While the EMEA is in favour of companies running randomized studies and comparing drugs head-to-head, there are situations where creating control groups is not so easy, said Dr Frank Giles deputy director of the cancer therapy and research center at the University of Texas Health Science Center. Recruitment for a large scale study can be problematic because the number of affected population is limited. It is estimated that there are approximately 10,000 – 20,000 new cases of MDS in the US each year.
Giles explained that Vidaza and Dacogen had only recently been approved for MDS at the time the company designed the study which could explain why they had not been included in a control arm. Still, Celgene could have designed a study comparing Revlimid to erythropoietin and growth factors, since they have traditionally been used to treat MDS, Giles suggested.
European doctors worry that when new drugs are not compared with the standard of care, patients’ well-being is placed at risk, said Dr Pavel Mohr a physician at Prague Psychiatric Center who has also worked in the US. Successful placebo-controlled trials of new drugs are usually enough to get a green light from the FDA, Mohr said, however, the regulatory environment in Europe is different and the EMEA would like to see that the efficacy of a new drug parallels those already on the market with positive results confirmed.
Still, the debate about how high to raise the bar for drug approval among physicians, biostatisticians and regulatory officials will always continue, said Dr Seema Singhal a physician at Northwestern University in Chicago. Insistence on running clinical trials which are both lengthy and costly, can delay the approval of drugs for conditions where little if any treatments are available. Singhal mentioned that if a drug is approved based on a single-arm clinical study, post-market clinical studies are vital to measure rare adverse events along with efficacy.
Peak sales of Lenalidomide are expected to generate USD 3.248bn in 2012.
Celgene has a USD 22.34bn market cap.
--------------------------------------------------------------------------------------------------------
For more information or to inquire about a trial please email sales@pharmawire.com or call Americas: +1 212-500-1384 or Europe: + 44 (0)20 7059 6251
