To address the current emergency caused by COVID-19, several initiatives have been undertaken at the regulatory level to promote and facilitate clinical trials and early access to drugs.
In particular, the following measures have been taken to ensure early access to therapies and to accelerate and facilitate clinical trials of new drugs for the treatment of COVID-19 disease:
- procedural simplifications for clinical trials and compassionate use programs concerning drugs to be used to treat patients affected by COVID-19, provided in Law Decree No. 18 of March 17, 2020 (“Cura Italia Decree” and Article 40 of Law Decree No. 23 of April 8, 2020 (”Liquidità Decree”)[1]; and
- off-label use of specific drugs already authorized for other diseases to treat patients affected by COVID-19 at the expense of the National Health Service (NHS).
Below is a more detailed description of such measures.
1. Cura Italia Decree and AIFA clarifications re: procedural simplifications applicable to clinical trials and compassionate use programs
The Cura Italia Decree (Article 17) introduced simplifications for the submission and approval of clinical trials of drugs for COVID-19, thereby accelerating the related procedures. Procedural simplifications have also been adopted for the compassionate use of investigational drugs for patients affected by COVID-19.
In particular, the Cura Italia Decree established that, for the duration of the state of emergency:
- the Italian Medicines Agency (Agenzia Italiana del Farmaco – “AIFA”) can access all data related to clinical trials and compassionate use of drugs for patients with COVID-19 in order to improve coordination and analysis of available scientific evidence;
- the Ethics Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome will be the only ethics committee in charge of expressing an ethical opinion on all clinical trials for COVID-19 with immediate effect throughout the entire national territory; and
- the Spallanzani Ethics Committee will also be tasked with approving requests for compassionate use of drugs for patients affected by COVID-19, with drugs supplied free-of-charge by pharmaceutical companies. In particular, requests for therapeutic use programs must be sent to the AIFA (for a preliminary opinion) as well as to the Spallanzani Ethics Committee. With regard to the application to AIFA, a derogation from the deadline of fifteen days prior to the start of the program is provided.[2]
To give further details and clarifications on the procedures to be implemented for the performance of clinical trials and compassionate use above, AIFA issued a note on April 6, 2020. That note indicates the minimum requirements for clinical trial proposals and observational studies and provides clarification on compassionate use programs for drugs under the Cura Italia Decree.
In particular, with regard to the procedures to be implemented for the compassionate use of drugs, AIFA specified that the simplified procedure provided by the Cura Italia Decree can be applied only to therapeutic use programs (i.e., programs offered by pharmaceutical companies for the compassionate use of a drug in several patients, based on a predefined and identical clinical protocol). Conversely, any requests for nominal therapeutic use for patients with COVID-19 (use of a drug outside the clinical trial for individual patients, not under a defined clinical protocol) shall continue to be submitted to the ethics committees of the relevant hospitals.
Compassionate use programs currently available for the treatment of COVID-19 include one for ruxolitinib (for patients diagnosed with COVID-19 and suffering from severe/very severe lung disease).
In addition, in its note, the AIFA provided clarification on the technical modalities for filings concerning authorizations to conduct clinical trials involving drugs to treat COVID-19, as well as observational pharmacological studies (i.e., studies relating to drugs used in normal clinical practice according to authorized indications).
The updated list of ongoing clinical trials is available on the institutional AIFA website. For instance, clinical trials involving tocilizumab and remdesivir are being conducted.
2. Off-label use funded by NHS
Due to the current health emergency and the absence of valid therapeutic alternatives, AIFA has allowed off-label use at the expense of the NHS of some medicines already authorized for the treatment of diseases other than COVID-19.
These AIFA decisions were taken, in certain cases, according to Law No. 648/96, which allows, in the absence of a therapeutic alternative, to supply at the NHS’s expenses: (i) not-authorized drugs, which are being tested; and (ii) drugs to be used for a therapeutic indication different from the authorized one.
In particular, Law No. 648/96 requires that in order for a drug to be included on the list of non-authorized drugs to be reimbursed by the NHS there must be studies—at least at the phase II level—available that demonstrate the efficacy of the drug, with an acceptable risk profile in support of the indication requested.
In other cases, AIFA decisions were taken in derogation of Law No. 648/96, since the relevant conditions were not met.
3. Next regulatory steps to boost COVID-19 research
Measures adopted so far are aimed at speeding up patients’ access to potential treatment for COVID-19 while the search for proper therapy continues.
To that end, the Ministry of Health recently launched a seven million euro call for proposals to promote research. Each selected project may receive up to one million euro. The aim of the projects should be to rapidly acquire knowledge about clinical measures that help improve patients’ health and limit the spread of COVID-19, enabling its management and resolution. The areas of investigation for the call include “treatment and management of the critical patient affected by COVID-19”.
Moreover, according to the Cura Italia Decree, AIFA shall issue an additional note to establish simplified procedures for accessing all data collected during clinical trials, pharmacological observational studies, and compassionate use programs, expected to offer great value for the development of any future therapy.
[1] In particular, Article 17 of the Cura Italia Decree was repealed by Article 40 (paragraph 8) of the Liquidità Decree and replaced by Article 40 of such decree, concerning “Urgent provisions on clinical trials of drugs for the epidemiological emergency due to COVID-19”. Article 40 Decree substantially confirms the content of Article 17 of Cura Italia Decree, with the following main news: (i) Article 40 only applies to clinical trials of drugs and not also to trials regarding medical devices; and (ii) it also addresses the management of phase I clinical trials, that were not regulated under Article 17 of the Cura Italia Decree.
[2] That derogation from the fifteen-day deadline is further clarified by AIFA on its website https://www.aifa.gov.it/web/guest/-/covid-19-precisazioni-su-definizioni-di-uso-compassionevole-e-relative-applicazioni-del-decreto-legislativo-18-2020
