Appeal type: Drugs
Decision: Unfavorable

We decided that the Plan does not have to pre-approve RADICAVA. You asked the Plan to pre-approve RADICAVA. You say that the requested RADICAVA is medically necessary. The Plan denied your request. The Plan says the requested RADICAVA is not medically necessary. The Plan must follow Medicare rules. The rules say that Medicare pays for a drug or biological only if it is safe and effective and otherwise reasonable and necessary. We asked our physician reviewer to carefully review the case file and apply the relevant Medicare rules to determine if the Plan was correct in denying the request to pre-approve RADICAVA. Our reviewer says that the requested RADICAVA is not medically necessary. Our physician reviewer found in this case the member has been prescribed RADICAVA for ALS. The drug has been approved by the FDA for use specifically in
patients with ALS. There were 3 major pre-market studies of RADICAVA. RADICAVA failed to show benefit in the first two trials of the drug. It was only the third trial in which a benefit of the drug was seen, and that third trial had specific indications for entry. In the first two trials (MCI-186-J16 and MCI-186-18) the authors concluded that, "No difference between edaravone (RADICAVA) and the placebo treatment was discerned in this exploratory study in patients with more advanced ALS". The drug was found to confer no benefit in patients who did not fall within the defined subgroup and such patients were excluded from the latter studies. This is also reflected within the Food and Drug Administration (FDA)-approved labeling for the drug.
The inclusion criteria was determined based on sub-group analyses of the prior two studies of the drug. It was in this third trial where RADICAVA was found to be safe and effective. In study number 3 (MCI-186-J19), subjects had to meet the following inclusion criteria: The patients had definite or probable ALS for up to 2 years and, were able to work or perform housework or were independently living but unable to work. Patients also had to have an ALSFRS-revised (ALSFRS-R) score change by -1 to -4 points during the 12-week pre-observation period, had a score of at least 2 on all 12 items of ALSFRS-R, and a forced vital capacity (FVC) of at least 80%. In this study of patients with ALS (N = 134), treatment for 24 weeks (6 cycles) with edaravone (RADICAVA) compared with the placebo significantly lessened functional decline as evaluated by the revised ALS functional rating scale score (ALSFRS-R; -5.01 versus -7.5). Edaravone (RADICAVA) was also associated with significantly lower decline in total modified Norris scale scores (-15.91 versus -20.8) and lower deterioration in quality of life (ALS assessment questionnaire, 17.25 versus 26.04). This study was the only one in which there was found to be a benefit from the use of RADICAVA. The enrollee's clinical information provided does not place her into the populations in which the drug has been shown (by current literature to be of benefit/utility). The member is noted to have a scores on the ALFRS-R below 2. In this setting, the drug is not reasonably expected to be of benefit/utility. Furthermore, the member's FVC is also reduced below 80%--another indication that suggests inferior outcomes with the use of the medication. In this setting and based on available literature it cannot be concluded that RADICAVA would be effective for the management of this enrollee's condition (it would have no effects on the course of the disease). We looked at this physician's review, the file, and Medicare rules. Based on this information, we decided that Medicare rules for coverage of RADICAVA have not been met. Therefore, we decided that the Plan does not have to pre-approve RADICAVA.