While most drugs are studied as a way to demonstrate benefit over other treatment, this trial of what could be described as a “last-ditch” drug–Lemtrada (alemtuzumab)–was studying optimal timing. Basically, is is better to give this drug more quickly, or only after trying other treatments?
This is a very important question and while this HealthDay story seems balanced, with numerous mentions of benefits and harms, there was a noted lack of a few key details, including the potential conflicts of interest among those who are pushing for quicker use of this treatment.
Readers need reminding that the manufacturer of a drug has an extremely strong interest in getting their drug used as early as possible in a disease process and that measures of “benefit” need to correspond to this early use. While the proponents say they believe giving the drug earlier may “slow and even reverse some disease-related disability,” others may demand a higher level of proof before exposing patients to this therapy.
No mention of costs, which we consider a major oversight. As a Boston Globe story explains: “Genzyme executives said Lemtrada will be priced at $158,000 for two courses of treatment over two years.”
For MS patients, this enormous price tag was a major point of discussion when the drug was first approved. “My excitement for Lemtrada’s possibilities as a treatment that brings us close to a cure for MS is dampened by the super inflated drug charges of 900% for each vial of alemtuzamab,” wrote Laura Kolaczkowski in a piece looking at the economics of this drug.
The story describes how the researchers assessed disability levels at the start of the study and every three months for two years. By the study’s end, nearly 28 percent of those given Lemtrada had improved by at least one point on a 10-point disability test, versus about 15 percent of those receiving interferon, the researchers found.
But the story said the patients randomized to Lemtrada were “2.5 times more likely to have their thinking skills improve compared to those given interferon. And they were more than twice as likely to see improvement in their ability to move without tremor or clumsiness, the findings showed.”
We need absolute numbers to compare what the baseline levels (thinking skills, move without tremors) were, and more details on what “improvement” means here, since this description alone doesn’t tell us if patients improved a little bit, or a lot.
Additionally, this statement had us scratching our heads: “Giovannoni believes the drug could offer real relief from MS symptoms. Not only does alemtuzumab improve disability, but most patients go into long-term remission of at least five to eight years, he said.”
Where did that determination come from? The study was only for two years and nothing presented within it showed remission.
The story mentions the risk of infections (including herpes), the need for monthly blood and urine tests for four years after the last dose, the risk of developing “another autoimmune disease,” such as Graves’ disease (a thyroid disorder) and a bleeding/bruising disorder called idiopathic thrombocytopenic purpura.
We’d have preferred to see a statement that long-term harms have not been determined, but this is otherwise a satisfactory description of the harms.
Also, the drug was initially refused approval by the FDA for safety reasons, a very revealing fact that would have provided patients with some context on how serious the side effects are.
Was the study randomized? Why was the intervention group twice the size of the control group? Were the investigators and patients blinded as to treatment? These are fairly important markers of quality which were missing from this report.
We also wanted to know how “newly diagnosed” these patients were, since that was the thrust of the story. All we’re told is “For this study, Giovannoni and colleagues treated 628 patients with relapsing-remitting MS who had not responded to at least one other MS drug.” (We looked it up–and “newly diagnosed” meant anyone who had been diagnosed within the last 10 years before joining the study.)
There was no obvious disease mongering. However, industry efforts to push very intense and very expensive drugs onto less-severely-affected patients should always be viewed with a healthy dose of skepticism. Do the benefits really outweigh the risks, or is this more about expanding the patient base?
Several potential conflicts of interest were not disclosed. From other sources, including here, we see that lead researcher Dr. Giovannoni receives consulting fees from Bayer Schering Healthcare, Biogen Idec, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratoires, Teva-Aventis, Vertex Pharmaceuticals, UCB Pharma, Pfizer.
And as for the source from the National Multiple Sclerosis Society, the society reported receiving nearly $2.6 million from the drug manufacturers who funded this study (Bayer and Sanofi) in 2015.
This study was comparing the new drug against interferon beta-1a, though we don’t get any sense of how it might have fared against the whole range of MS drugs currently being used.
The story states that the drug is approved in the U.S. for patients who have failed other treatments.
The story establishes the novelty by explaining that this study showed the drug could be used in more newly diagnosed patients:
Because of serious side effects, the drug — Lemtrada (alemtuzumab) — is approved in the United States only for patients who have failed other treatments. But the authors of a new study believe giving it early may slow and even reverse some disease-related disability.
The story does not appear to rely on a news release.