An example of regulatory and HTA misalignment around UMNs: Polivy for diffuse large B-cell lymphoma in France
The absence of a shared understanding of UMNs can lead to inconsistent decisions or priorities between stakeholders, leading in turn to delays or barriers to development. We suggest that such a misalignment explains at least some of the experience of Polivy (polatuzumab vedotin) under France’s Temporary Use Authorisation (ATU) scheme.
The primary objective of the ATU is accelerated patient access to promising medicines not yet covered by a marketing authorisation in France, particularly in areas of recognised UMN. To achieve faster access, promising medicines are made available through the ATU before they are granted European Medicines Agency marketing authorisation and before an HTA reimbursement decision is made. There is an evidence generation element in the ATU, but in contrast to “coverage with evidence generation” schemes such as the UK’s Cancer Drugs Fund, this is not a primary objective of the ATU and the data generated through the scheme are not typically a critical element of the HTA
Polivy—a first-in-class treatment for diffuse large B-cell lymphoma, a rare but fatal condition—was accepted into the ATU on the basis of a phase Ib/II study [7, 8] and authorised for use by the European Medicines Agency [9]. However, France’s HTA agency, the Haute Autorité de Santé (HAS), subsequently rejected Polivy for reimbursement on the basis of the same package of evidence submitted to the ATU [10]. The HAS judged that Polivy “did not provide a sufficient medical benefit or public health benefit to justify a place in the treatment of adult patients …” [10]. It is notable that HAS’s judgement did not reference value for money and appears to be based entirely on perceived health benefits.
There is considerable overlap in the criteria for ATU eligibility and HAS reimbursement: both emphasise relative efficacy/effectiveness and safety, disease severity and rarity, and the availability of alternative therapies [11, 12]. However, ATU deemed Polivy to be promising enough in addressing a recognised UMN to grant accelerated access, whilst HAS saw essentially the same evidence as insufficient to justify a place in treatment. This outcome suggests an important misalignment in understanding between two closely related agencies that should, in principle, be working in concert. Similar misalignment between regulators and assessors has been noted elsewhere, [13] and represents a key barrier to effectively addressing UMNs.