FDA places a partial hold on all venetoclax clinical trials for multiple myeloma (MM) patients
Usually the USA leads the way in drug approval and availability (if not affordability), of novel agents, but this time the United Kingdom, by their regulatory authorities approving more liberal and in my mind, more appropriate indications for the use of venetoclax (the American brand name is VENCLEXTA) in chronic lymphocytic leukemia, is the leader. But they still could have done better
In the USA, here is the one and only indication approved by the FDA. This text is taken directly from the package insert for venetoclax.
- VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.
In the United Kingdom, approval of new drugs is done through the National Institute of Health and Care Excellence with the lovely acronym of NICE.
The regulators in England make no pretense that their decisions are dependent on anything more than the cost/benefit ratio.
From the outside, it certainly appears that approvals are sometimes delayed as a tactic to negotiate lower prices from the pharmaceutical companies. Lower the cost of drug acquisition and the cost/benefit ratio improves. Patients needing the medicine immediately are the losers in this game.
NICE has recently decided that venetoclax should be funded through the government’s health services to treat CLL patients in England in the absence of 17p deletion or TP53 mutation who have failed both chemo‑immunotherapy (CIT) and a B-cell receptor (BCR) inhibitor.
This is a broader indication than in the USA where it is not approved in the absence of 17p deletion and that more liberal UK approval is most welcomed. Still, why must NICE force every patient without 17p deletion to fail CIT before being offered venetoclax. For many patients, CIT is not the best choice, but is now part of the required path to venetoclax in the UK for those without a 17p deletion.
Venetoclax has also been recommended by the UK cost regulator for those with CLL who carry the 17p deletion or TP53 mutation and who are either unsuitable for or have failed a BCR inhibitor.
This is a little different and more restrictive compared to the USA, where the only requirement for those with 17p deletion is to have ”received” a prior therapy, making it easier for those patients to get the drug.
Of course, any drug can be used off-label, but due to its high cost, it will be a challenge with venetoclax to get insurance or the government to cover it beyond the approved indications.
Clinical trials are often the best to go to gain access to new medications and this path has several advantages in this particular circumstance:
- Venetoclax may be only available in clinical trials in countries where it has not yet been approved.
- The venetoclax and any other drugs in the trial are usually free. This is particularly critical in the USA.
- Venetoclax is often being used in combination with other medication such as obinutuzumab or ibrutinib in trials. Early research with admittedly small numbers of patients has demonstrated improved outcomes over single agent venetoclax.
- Monitoring is close in trials and the doctors are usually more experienced in the use of a novel agent, such as venetoclax.
Here is a link to an article on the UK approval.
http://www.pharmatimes.com/news/abbvies_venclyxto_now_available_through_cdf_1207179
One of the critical details in that article is the almost casual mention of the chilling fact that most patients who eventually require treatment for their CLL (at least 70% of us will need treatment at some time) will eventually fail that treatment.
Venetoclax is a powerful and effective next step, helping about 80% of the most difficult-to-treat patients, but its durability is still a hot area of research.
We are still looking for that knockout punch in CLL.
Brian Koffman, MD 10-24-17
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