June 19, 2012 4:55 pm
This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com
Celgene’s (NASDAQ:CELG) cancer blockbuster Revlimid (lenalidomide) will face reimbursement challenges in Europe if approved for wider use, experts told Biopharm Insight.
Revlimid was approved in 2005 for previously treated patients with multiple myeloma (MM), a cancer of plasma cells in the bone marrow, in combination with generic dexamethasone.
Since approval, physicians have debated the benefit of Revlimid as a frontline, or first-line induction therapy in MM. Celgene is currently in regulatory discussions for a extended label. The drug is also gaining traction as a maintenance therapy, for which the company is also seeking approval.
Although the drug has been clinically proven as a valuable first-line therapy for MM, and as a second line combination agent, pricing and a lack of survival benefit will likely create push-back from EU payors if approved for wider use.
Celgene did not return comment.
Revlimid’s off-label use in frontline MM therapy has been adopted as standard of care, and the drug is readily reimbursed in the US despite a lack of approval in this setting, said one oncologist. In the EU, clinicians cannot access Revlimid outside of a clinical trial for frontline use, he said, adding they are waiting to use it earlier but it is very expensive.
Celgene has three pivotal studies (MM-015, IFM 0502 and CALBG) ongoing and has reported interim efficacy results that demonstrate additional benefit in newly diagnosed multiple myeloma patients as a frontline therapy.
The overall risk-benefit profile is still in question since myeloma is a chronic disease, making the management of toxicity an important consideration, one oncologist said. However, Revlimid has demonstrated quality of life and a progression-free survival (PFS) benefit, she noted.
There is a definite PFS benefit but there was not an OS improvement in the MM-015 trial or IFM study, the first oncologist said. While CALGB did show a benefit in certain subgroups, the data was “highly worked,” he claimed.
Furthermore, one of the most frequently used therapies for multiple myeloma, Takeda’s (TYO:4502) Velcade, increased OS when used as an induction and maintenance therapy compared to conventional induction and thalidomide maintenance treatment, the first oncologist said.
This news service previously reported the IFM study is expected to eventually show Revlimid has an OS advantage.
OS is always the gold standard and should be demonstrated for complete adoption into the clinic, the second oncologist said. Demonstration of a PFS benefit with so many third- and fourth-line options is not as impressive, she added.
EU reimbursement authorities are now increasingly looking for a statistically significant OS benefit, said one reimbursement expert. Even if the company gets approval as first-line therapy, reimbursement will only come once survival data is achieved, he added.
A second reimbursement expert said at the current annual price of EUR 60K, Revlimid will have challenges as first-line therapy over thalidomide and Velcade -- which are much cheaper alternatives at EUR 8K-16K, and are dose-dependent.
Celgene has made an agreement with local agencies, putting a ceiling on the cost per-patient per-lifetime and many payors agreed to just one year, the second reimbursement expert said. Extending the label just increases this population, and given the current austerity measures, local EU authorities will be reluctant to pay for it, he said.
To show an OS benefit is not easy and takes a lot of data and time, a third reimbursement expert said. In this current environment, regulators are cautious to reimburse oncology drugs without OS data, the third expert added. The level of benefit required differs country to country, he noted.
A fourth reimbursement expert said obtaining reimbursement in the UK will be the most difficult. Other EU reimbursement authorities are often influenced by key opinion leaders (KOLs), and he highlighted the German Authority, The Federal Joint Committee (G-BA) and the French National Authority for Health (HAS), as examples.
If KOLs push for first-line use, it could impact reimbursement discussions, the same expert said. KOLs are an integral part of the process, although pricing is likely to stand in the way in this case, he added.
The European Health Technology Assessment (HTA) will debate how statistically significant a survival benefit has to be, whether it is one week, one month or a year, and the cost-benefit, said the first reimbursement expert. If anything, Revlimid will likely be limited to certain populations showing the greatest benefit from earlier use, he added.
Revlimid’s lack of benefit in patients over 75 years of age in the MM-015 trial -- patients were 65 years and older -- is likely attributable to the general frailty of the group, the first oncologist said. The European Medicines Agency (EMA) may include a label restriction for use in elderly patients, he added.
It is important to balance the risk-benefit assessment for each patient, the first oncologist said, as Revlimid as a first-line therapy is not the best option for everyone.
The MM-015 trial will form the basis of the EMA’s decision, he said, and the FDA is expected to follow suit.
Phase II data shows a benefit of Revlimid when given upfront and in a continuous fashion, as 75% patients who stayed on treatment had disease-free survival over two years, the first oncologist noted.
This data has been submitted for publication, and three publications are expected this year – namely the MM-015, IFM 0502 and CALBG trials, he said.
Celgene has a market cap of USD 31bn
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