Translation of a-t 2025; 56: 47

Not a matter of course – ineffective medications should be removed from the market

Approved medicinal products must be "safe and effective". If the data situation changes as a result of new findings on risks, these are communicated where applicable in the form of dear healthcare professional letter or they lead to market withdrawal. But what happens if the benefit of an approved medicinal product cannot be proven by current, conclusive studies despite descriptions of effectiveness that had been accepted by the authorities in the past? Probably nothing, because subsequent doubts about the effectiveness are not one of the statutory reasons for approval to be withdrawn.¹ Once marketing authorisation had been granted, despite insufficient evidence of the benefit of injections of inactivated streptococci (STROVAC) for urinary tract infections and despite a subsequent negative study, the competent Paul Ehrlich Institute does not see this as a legally permissible reason to request that the provider conducts an efficacy study (a-t 2024; 55: 54). Just under 50 years ago, the US drug authority, the FDA, initially classified phenylephrine per os, which was said to alleviate the symptoms of a blocked nose in cold medicines, as "safe and effective".² Based on an assessment of the current knowledge, the authority no longer considers the peroral sympathomimetic to be effective.^2,3 Even at doses higher than those recommended, it does not differ from a placebo in terms of alleviating a blocked nose (a-t 2023; 54: 70). Regulatory measures are expected in the US from the second half of 2026.⁴ Late, but still. The European Medicines Agency, EMA, however, is not carrying out any activities with the aim of reassessing the effectiveness of peroral preparations containing phenylephrine,¹ one million packs of which are sold in Germany each year, predominantly GELOPROSED (60%) and WICK DAYMED Kombi, OTRICOMPLEX and DOREGRIPPIN. In response to our question about providers taking measures themselves, they refer to the positive assessment at the time of the approval and to the responsibility of the authorities.^5,6 Another problem is accelerated approvals, the goal of which is to meet an unmet medical need but which can be done on the insubstantial basis of surrogate criteria or interim results. If there is no evidence of a benefit in confirmation studies, the approval is by no means automatically withdrawn. The COX-2 inhibitor celecoxib (ONSENAL) was approved using an accelerated procedure for patients with familial adenomatous polyposis without proof of protection against bowel cancer or in rarer cases surgery. Pfizer only gave up the EU approval eight years later when a benefit could still not be proven.⁷ Premature approval can even prevent the necessary confirmation studies from being conducted if study participants reject a placebo citing the existing approval.⁸ If medicinal products for which no viable evidence of effectiveness is able to be obtained even after years, which is certainly common with cancer drugs, for example,⁹ this can mean avoidable adverse reactions occurring, potentially effective therapies being withheld and resources being wasted, in addition to giving patients and prescribers false hope. Long-term marketing without evidence of effectiveness serves the commercial interests of the provider but not of the health of those treated. Legal framework conditions that provide for official measures or the withdrawal of an accelerated approval – for example in case of justified suspicion of ineffectiveness – if the confirmation data are not submitted within a defined period of time would contribute significantly to preventative consumer protection. Drug authorities should also use accelerated approval procedures less frequently and return to robust evidence requirements,¹⁰ –Ed.

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