European Medicines Agency committee. Yesterday, the Committee for Medicinal Products for Human Use (CHMP) issued a formal recommendation against approval of the Marketing Authorization Application (MAA) of Qsymia (Qsiva) in the European Union.
Several American doctors were hoping that Qsymia would also get rejected in the US, but earlier this year the FDA approved Qsymia and to the surprise of many, the REMS program put in place was much more lenient than many had hoped for. Before Qsymia's approval many wrote to FDA warning it of dangers of Qsymia, but these calls fell on deaf ears.
At the same time, there may have been lobbying by powerful hedge funds and political powers who back Vivus, possibly the same group who were lobbying against Arena Pharmaceuticals' (NASDAQ: ARNA) Belviq (and who all turned out to be wrong when the FDA decided to side with science and not Wall Street's fiction, and approved Belviq). A large number of people, including doctors and patients, demanded FDA's approval of Belviq.
After approval of Qsymia in the US, some American doctors were appalled by what they viewed as an irresponsible decision by the FDA. One of the key risks of Qsymia is birth defects. Dr. Daniel P. Lopez, M.D., F.A.C.O.G., an obstetrician and gynecologic surgeon in Los Angeles, in a recent posting blasted the FDA for their approval of Qsymia. Dr. Lopez cited a survey reported on WebMD.
Dr. Lopez wrote: "A survey reported on WebMD "2 in 5 Women Don't Use Birth Control: Many Women Mistakenly Believe They Can't Get Pregnant" reveals that many women don't use contraception and the ones that do don't use it properly:
- 43% of women who had been pregnant had one or more accidental or unintended pregnancy
- About 50% of these women report that at least one of these pregnancies may have been caused by birth control failure, such as a broken condom.
- One in 10 women on birth control reported a perceived failure in the past year.
This makes the lack of FDA compulsory pregnancy testing in the Qsymia REMS even more disconcerting. Despite the physicians asking the patients to use birth control while on Qsymia they will still have a high percentage of patients who will get pregnant while on the drug. Shame on you FDA."
Europe saw through the hype and rejected Qsymia. In a press release, Vivus indicated the reasons as:
"due to concerns over the potential cardiovascular and central nervous system effects associated with long-term use, teratogenic potential and use by patients for whom Qsiva is not indicated."
Europe's strong wording against what some social media participants have called a “toxic cocktail” -- phentermine/topiramate combo drug Qsymia -- should be a wake up call for the FDA to at least reject Vivus' recent request to make an already too lenient REMS program even easier.
FDA would allow refractory heterozygous FH trial, but AEGR also must do high risk HeFH trial, and may need clinical outcomes trial. AEGR has not pursued any of these options, at least in part due to financial constraints.
• including patients with 300 LDL mimics the severe refractory HeFH population and shifts risk/benefit (untreated HoFH have LDL 650 mg/dL) -this would be a REMS issue
• safety, but not effiacy data for weeks 56 through 78 have been submitted to the NDA
• It seems unclear whether lomitapide would be approved for patients with liver related abnormalities based on clinical pharmacology comments - what portion of the market would this represent?
• 24/28 patients (86%) had 10% increase in % hepatic fat (absolute points, see figure below) - patients with diabetes or alcohol consumption were excluded from study but have greater risk of steatosis. 26% missing data - may be biased and missing subjects with large amounts of fat at follow-up. appears reversible (not always), at least after short term use
• substantial fat accumulation even in the clinical trial with lower risk patients at lower doses of 2.5-10 mg.
• investigators were not blinded to LDL levels - potential bias source