Old but unfortuntely still actual
The German IQWiG Confuses Enrollment Criteria with Mechanism of Action
In Germany, the Institute for Quality and Efficiency in Health Care (IQWiG) provided the scientific evaluation of IPE. It claimed that IPE was not compared to a maximally optimized LDL-C lowering therapy called the accurate comparator therapy (ACT), making it impossible to isolate its efficiency (see annex 23). It stands alone in this assertion, as it is contradicted by IPE's approval by all major regulatory agencies. The IQWiG appears to have erroneously conflated the REDUCE-IT trial's requirement that all patients be on statin therapy with LDL-C lowering itself, mixing up enrolment criteria with the mechanism of action. Rationality dictates that drugs should be tested based on their biological targets or mechanisms of action, not according to enrolment criteria, which only define the targeted population. IPE does not pursue LDL-C lowering.
IQWiG’s request that LDL-c therapy be maximized only makes sense when evaluating a drug intended to further lower LDL-C levels beyond what existing therapies can achieve. In contrast, IPE, as any non-LDL-C lowering drug, provides cardiovascular benefits independent of further LDL-C reduction. These drugs are compared to their own benchmarks. For example, a new anti-hypertensive drug is benchmarked against the best current blood pressure-lowering treatment but not against an LDL-C lowering therapy. If a drug, like IPE, is the first in its category it has to be compared to a placebo and not to an optimized LDL-C lowering therapy.
In clinical trials like REDUCE-IT, contrary to IQWiG’s assertion, ensuring standard medication consistency across groups (e.g., LDL-C lowering, blood pressure-control, diabetes treatment) is sufficient to isolate the new drug's specific effects. This is standard practice. Trials testing SGLT2 inhibitors, GLP-1 receptor agonists, colchicine, or Rivaroxaban did not require strict LDL-C control as now requested only for IPE, yet cardiovascular benefits were evident.
This lack of understanding from the IQWiG’ committee in charge of the assessment is bewildering and has two consequences.
IQWiG's Self-Inflicted Impossibility:
Imposing this irrelevant ACT criterion would unduly restrict icosapent ethyl (IPE)'s application, limiting its use to patients with extremely low LDL-C levels, should a new trial adhering to their requirements ever be conducted. This would be really absurd and a major waste for patients given its proven efficiency at any LDL-C level below 100 mg/dl.
Double Standard:
No non-LDL-C lowering drug has ever been restricted to this extremely low LDL-C levels.
A scandal in the making?
The Federal Joint Committee (G-BA), Germany's top healthcare decision-making body, cannot contradict the EMA's approval of Vazkepa, but it can set its price based on perceived cost-effectiveness. By setting remarkably low prices for Vazkepa, comparable to those of mere supplements, the G-BA effectively endorsed the deeply flawed IQWiG's assessment of icosapent ethyl's value, making economically unfeasible for Amarin to promote Vazkepa. This has led to Amarin's justified refusal to accept these terms, resulting in unnecessary delays.
Delays in drug approval are normal, yet unreasonable delays are indefensible. The longer these extraneous delays persist, the higher the risk of pointless deaths and CV events. It is imperative that the German agency act promptly to rectify its misunderstanding of Vazkepa efficacy.
Bullish
