Compassionate Use Program

CUP is an arrangement that manufacturers can use to make a medicinal product available for a group of patients, prior to the marketing authorisation (MA) approval.

Requirements for Compassionate Use

A CUP can only be initiated after NOMA has assessed and approved the application. The manufacturer of the relevant medicinal product applies for this approval.

The following conditions/requirements must be met:

• The medicinal product in the program is intended exclusively for patients with chronic, life-threatening, long-term, or severely debilitating diseases.
• The medicinal product in the program is only for patients who cannot participate in ongoing studies and who do not benefit from treatments involving medicinal products with existing marketing authorisation.
• Adequate documentation must be available to demonstrate the efficacy and safety of the medicinal product, with a benefit-risk profile considered overwhelmingly positive for the target patient group.
• The applicant must have submitted a marketing authorisation application and/or be conducting ongoing clinical trials for the relevant product.

Overview of current and discontinued programs

NOMA publishes information about the medicinal products included in CUP. This includes details on the active substance, trade name, indication, and the name of the manufacturer.

CUP available for patients

CUP available for patients

Active substance	Indication	Date of approval	Responsible for the CUP
Belantamab mafodotin (GSK2857916) 2.5 mg/kg / 1.9 mg/kg solution for IV infusion	Multiple myeloma	2025-01-28	GSK Norway Contact person: Janne Beheim Mobile: +47 99 27 24 89 E-mail: janne.x.beheim@gsk.com
Obnitix	Grade II-IV acute Graft versus Host Disease (aGvHD) following allogeneic stem cell transplantation (alloHSCT)	2025-03-19	Medac Addresse: Hyllie Boulevard 34 | 215 32 Malmö, Sweden Contact person: Annette Dahlberg Phone: +46 76 112 03 79 E-mail: a.dahlberg@medac.se
Nimorazole tablets, 500 mg	Squamous cell Cancer of the Head and Neck (SCCHN)	2016-12-01	Afyx Therapeutics Contact person: Pernille Træholt  Email: RA@afyxtx.com Phone: (+45) 7174 7174

CUP no longer available for new patients

CUP no longer available for new patients

Active substance	Indication	Date of approval	Responsible for the CUP
Sipavibart   (AZD3151) 150 mg/mL solution for injection	Pre-exposure prophylaxis of COVID-19 for immunocompromised individuals	10.04.2024	AstraZeneca Nordic
Elranatamab (PF-06863135) 40mg/ml	Multiple Myeloma (MM)	02.02.2023 Ended: January 2024	Pfizer AS
Glofitamab (AG42296) 5 mg/ml solution for iv infusion	Relapsed / refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL), transformed Follicular Lymphoma (tFL) or Primary Mediastinal B-Cell Lymphoma (PMBCL)	20.05.2021	Roche Norge AS
Tebentafusp (IMCgp100) 0.2mg/mL solution for infusion	HLA-A*02:01 positive patients with unresectable or metastatic uveal melanoma	16.01.2022 Ended: May 2023	Immunocore, Ltd.
Mosunetuzumab (AG42295) 1 mg/1 mL, 10 mg/10 mL og 30 mg/30 mL	Relapsed / Refractory Follicular Lymphoma (R/R FL)	14.10.2021. Ended: 2022-	Roche Norge AS
Pevonedistat (TAK-924/MLN4924 10 mg/ml consentrate for solution for iv infusion)	Higher risk myelodysplastic syndromes (HR-MDS), or low blast acute myelogenous leukemia (LB- AML)	25.08.2020	Takeda
Risdiplam (RO7034067)  60mg, mixture	Spinal muscular atrophy (SMA)	08.05.2020	Roche Norge AS
Zanamivir 10mg/ml Infusion bag.	Hospitalised patients severely ill with influenza infection	25.02.2011	GlaxoSmithKline Research & Development Limited, United Kingdom
Polatuzumabvedotin, 140mg concentrate for infusjon	Relapsed or refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL)	01.02.2019	Roche Norge AS
Entrectinib capsules, 100mg, 200mg	Solid Tumors harboring a NTRK Gene Fusion or Patients with Non-Small Cell Lung Cancer (NSCLC) harboring a ROS1 Gene Fusion (AG40852)	07.03.2019	Roche Norge AS
Quizartinib tablets, 20mg and 30mg	Relapsed or Refractory Acute Myeloid Leukemia (AML) with FLT3-ITD mutations	12.03.2019	Daiichi Sankyo Inc.
Lorlatinib tablets, 5mg, 25mg, and 100mg acetate solvate tablets or as 25mg or 50mg free base tablets	Advanced non-small cell lung cancer (NSCLC) with an ALK or ROS1 gene rearrangement	05.09.2018	Pfizer Norge AS
Brigatinib tablets, 90 mg and 180 mg	ALK positive Non-Small Cell Lung Cancer	20.04.2018	Takeda Pharmaceuticals AS,
Emicizumab, 150 mg/1 ml	Hemophilia A and FVIII Inhibitors	01.11.2017	Roche Norge AS
Orcrelizumab, 300 mg intravenous infusion	Primary Progressive Multiple Sclerosis (PPMS)	07.06.2017	Roche Norge AS
Pembrolizumab, intravenous infusjon 2 mg/kg	Metastatic Melanoma	09.09.2014	MSD Norge AS
Ibrutinib capsules, 140mg	Relapsed or Refractory Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma with Deletion 17p	06.05.2014	Janssen-Cilag AB
Cobimetinib (GDC- 0973) 20 mg	advanced/metastatic BRAFV600 mutation-positive melanoma	25.06.2015	Roche Norge AS
Combination regimen of trametinib and dabrafenib. Dabrafenib 150 mg Trametinib 2 mg	BRAF activating mutation- positive metastatic melanoma	22.08.2015	GlaxoSmithKline (GSK) AS, Oslo
Daclatasvir, 60 mg	Chronic hepatitis C	23.06.2014	Bristol-Mayers Squibb AS
Boceprevir	Hepatitis C	05.05.2011	MSD
Abiratrone	Metastatic Advanced Prostate Cancer	19.11.2011	Jansen Cilag
Crizotinib (PF- 02341066)	Cancer (Positive ALK- fusion)	13.10.2011	Pfizer
Aflibercept	Metastatic Colorectal Cancer (mCRC)	28.09.2011	Sanofi

Application for CUP

Cover letter

There is no dedicated application form for CUP. The necessary information (as described below) must be included in the cover letter.

 

Information on clinical trials for the medicinal product

Information must be provided regarding the clinical trials that have been conducted or are ongoing for the relevant product. If previous studies have been conducted in Norway, please reference the EudraCT number and/or EU-CT number, along with NOMA's reference number.  

Information on application for Marketing Authorisation (MA)

Information about the Marketing Authorisation must be included in the cover letter. In the case that the application has been submitted, the reference number and the date of submission should be provided. This information can be included in the cover letter.

Justification

A justification must be provided for the use of compassionate use, explaining why patients cannot be adequately treated with approved medicinal products. Additionally, it must be clarified why there is a compassionate use program in place, and not a clinical trial.

Safety monitoring

The application must contain a description on how adverse reactions will be recorded and reported.

Protocol (project plan)

There are no formal requirements on the content of a protocol for a CUP. ICH E6 R3 (GCP)(External link), Appendix B can be used as a guideline.

Informed consent sheet

There are no formal requirements for the content of the patient information for a CUP.  The template for information sheets used in clinical trials, published by REK(External link), can be used as a guideline.

Labelling

An example of the labelling intended for use in the CUP must be included with the application. Medicinal product in CUP should be labelled as medicinal products in clinical trials.

Assessment of the benefit-risk ratio

Unless described in the CUP protocol, a benefit-risk assessment must be included in the cover letter, highlighting the risks associated with using the CUP medicinal product in relation to the potential benefits for the targeted patient group participating in the CUP. The benefit-risk assessment for the patient population should be based on a compilation of results from clinical studies conducted for that indication.

 

Documentation of the medicinal products

• Clinical and Preclinical Documentation: Investigator's Brochure.
• Quality Documentation: If the application involves the use of a new active substance or a new formulation of an authorised active substance, quality documentation related to this must be included with the application.
• Overview of Clinical Trials: A summary of completed and ongoing clinical studies must be provided. The studies should be identified using NOMA's reference number (if studies have been or are being conducted in Norway) and the EudraCT number and/or EU-CT number.

Contact information

The following contact details must be provided in the application: Name (CUP contact person), Company, Address, Phone Number, and E-mail Address. This information will be made available on NOMA's website; please refer to the Overview of current and discontinued programs (please see above).

 

Financing the medicinal product

The pricing of medicinal products included in a CUP is to be agreed upon between the pharmaceutical manufacturer, the treating institution, and, if applicable, the pharmacy. Medicinal products provided through a CUP must be free of charge for the patient.

Authorisations import and manufacturing

The import of medicinal products for a CUP follows the same regulatory requirements as the import of other medicinal products. Import is carried out by entities holding import authorisation or by hospital pharmacies that can import by virtue of being a pharmacy. Within the EEA, only import authorisation is required, whereas outside the EEA (third countries), a manufacturing authorisation is also necessary.

Manufacturing authorisation is granted by NOMA and requires, among other things, that the importer has a Qualified Person (QP) responsible for ensuring that professional requirements related to both the medicinal product and its transportation are met and to oversee compliance with professional standards for imports from countries outside the EEA.

Assessment and approval

There is no statutory deadline for NOMA's assessment of these applications. NOMA aims to respond to CUP applications within 35 days. 

The application must meet the requirements of compassionate use program and include all required documentation for the review process to begin (see above).

Decisions on CUP applications are taken by NOMA in accordance with § 2-8 in the Norwegian Regulation on Medicinal Products.

NOMA may impose a time limit or other conditions on the approval of a CUP. If an extension is needed beyond the approved timeframe, an application for the extension must be submitted.

There is no fee for Compassionate Use Program applications.  

Follow-up after the approval of a CUP

List of participating patients

The treating physician must maintain a list of patients included in the program. This list should be continuously updated as new patients are enrolled.

Adverse reaction recording and reporting

Adverse reactions in a CUP must be reported in the same manner as for marketed products. See Regulation (EC) No 726/2004, Article 24(1) and Article 25.

Substantial amendments

If the applicant wishes to make substantial amendments to the protocol, the amendment must be submitted for approval by NOMA. Substantial amendments are defined as those likely to have a substantial impact on patient safety or physical/mental integrity, or on the quality and safety of the investigational medicinal product. The same principles as for amendments to clinical trials apply. If NOMA does not object to the amendment within 35 days, the application is considered approved.

Reporting

The applicant must annually submit a status report to NOMA. The report must include the number of patients included in the program, an assessment of the risk-benefit ratio for the product in the program, and a line listing of all serious events.

Marketing authorization obtained for the medicinal product

When a medicinal product used in a compassionate use program (CUP) receives marketing authorization and pricing, the marketing authorization holder must send updated information to the DMP within 30 days about the planned end date or whether the CUP should be continued for patients who benefit from the treatment. Patients already included in a compassionate use program may continue in the program after the medicinal product has received marketing authorisation and pricing approval if the treating physician deems this necessary for the patient.

New patients may be included until the medicinal product has been priced and is commercially available in Norway. ​Please, also see website Nye Metoder for information (only available in Norwegian).

Termination

NOMA can terminate a CUP if it is deemed necessary, for safety reasons or following other relevant considerations.