In 2016 EMA annual report, that recently was in the spotlight of our news section, the agency seemed very proud of joint (EMA-FDA-PMDA) accelerated approval procedure existence and execution. Yet, industry also needs it to be reviewed from external point of view to consider all the risks and benefits.
Products came to market as FDA approved ones, when there is not enough clinical safety and efficacy data yet. A case with bevacizumab in breast cancer, when the drug resulted being not as safe and effective as in preliminary studies, depicts the risks of accelerated drug approval clearly. Recent publication in NEJM also points on the most fragile spot in the procedure – cost of rapidly approved drug and issues related to insurance coverage. For example, eteplirsen was given accelerated approval for use in muscular dystrophy in September 2016 based on very small increase in the production of dystrophin protein; controversy ensued about whether such increase could actually affect clinical progression of the disease. When it received the approval, the manufacturer announced a price of $300,000 per year or more, depending on the patient’s weight. One US insurer declined insurance coverage for eteplirsen completely, another agreed to cover it only conditionally.
Medicaid program tried to limit coverage for new anti-hepatitis C drugs, but that resulted in failed lawsuit for imposing allegedly improper prior-authorization requirements.
Thus, at a time when medications can cost hundreds of thousands of dollars per year, accelerated approval can lead to situations in which private payers may choose not to cover a drug, while major government payers are forced to cover the product, directing substantial tax dollars to drugs not yet shown to have clinical benefit.
Publication authors suggest several solutions. First, manufacturers could be obliged to offer additional price concessions to public insurance programs for drugs receiving accelerated approval until the confirmatory trials are completed. A portion of the drug payment could be held until drug’s efficacy is confirmed.
Second, it would be feasible to see the FDA do more to ensure that confirmatory trials conducted after receiving accelerated approval are performed in a timely fashion. Authors propose that there should be plans in place to begin confirmatory trials within 3 months after approval, with tracking of trial progress through ClinicalTrials.gov.
Finally, authors propose that all drugs that move through the accelerated-approval pathway and cost over $100,000 per year, or some other agreed-on threshold, should be the subject of formal economic impact analyses after 1 to 2 years on the market.
Accelerated drug approval procedure should certainly not be a coverage for unreasonable pharma profit, it is intended to save lives, and should be attractive to insurers. Implicating measures proposed in the article will certainly help market of unique drugs to maintain it’s attractiveness for insurers but there is still way to go in this direction.