Janssen announced that bortezomib, a treatment for adults with multiple myeloma, is now licensed in the UK for subcutaneous administration within its licensed indications.

This provides an alternative to intravenous administration, the route of administration for which this medicine was initially licensed and which can still be used.

Bortezomib is the first of the class of anti-cancer drugs known as proteasome inhibitors.

Commenting on the approval of bortezomib for subcutaneous administration, Professor Graham Jackson, Consultant Haematologist at NCCC, Freeman Hospital, Newcastle Upon Tyne, said: “The subcutaneous route of administration for bortezomib is an advance that could confer important benefits in a clinical setting. It offers the potential for reduced time in the clinic, making it more convenient for both healthcare professionals and patients alike. Subcutaneous administration could also be particularly beneficial for those patients with poor venous access, those with pre-existing peripheral neuropathy, or those at high risk of developing peripheral neuropathy.”

By eliminating the need for repeated intravenous access and/or insertion of a long-term central venous device, and there being no need to dress the injection site, subcutaneous administration could save on staff nurse time.

Subcutaneous injections are administered at 2.5 mg/mL (3.5 mg bortezomib reconstituted with 1.4mL normal [0.9%] saline) to limit the volume injected.1,4 This is a higher concentration of bortezomib to that used intravenously, which means that the same amount of medication is delivered through a smaller volume.

Myeloma is the second most common type of blood cancer, representing about 15% of all blood cancers in the UK5 and 1.5% of all cancers (about 3 in every 200). Just under 4,800 people in the UK are diagnosed with myeloma each year.6

Eric Low, Myeloma UK Chief Executive said "Today’s decision by the European Commission to approve the use of subcutaneous Velcade in Europe is good news. It is now important that clinical practice across the UK changes in a timely and effective manner to ensure that myeloma patients benefit from subcutaneous Velcade as soon as possible’’.

The approval is based on results from a randomised, phase 3, open-label, international trial conducted in 222 bortezomib-naïve patients with relapsed multiple myeloma, the results of which were published in the Lancet Oncology in May 2011. This pivotal study clearly showed that subcutaneous bortezomib was non-inferior in terms of efficacy compared with intravenous administration, with an improved safety profile. Patients receiving bortezomib subcutaneously achieved a 4-cycle overall response rate (ORR; complete response [CR] plus partial response [PR]) of 42% and CR of 6%, while patients receiving bortezomib intravenously achieved an ORR of 42% and a CR of 8%.4

Peripheral neuropathy is a well known, and for some patients treatment-limiting, side-effect of bortezomib, and subcutaneous administration was seen to significantly reduce bortezomib-related peripheral neuropathy. In the subcutaneous arm of the trial, 6% of patients experienced peripheral neuropathy of grade 3 or higher, compared with 16% in the intravenous arm (p=0.026). In the subcutaneous arm, 38% of patients experienced peripheral neuropathy of any grade, compared with 53% of patients in the intravenous arm (p=0.044).

Grade 3 or worse adverse events were reported in 84 (57%) patients in the subcutaneous group versus 52 (70%) in the intravenous group; the most common were thrombocytopenia, neutropenia and anaemia. Serious adverse events were reported in a similar proportion of patients. Overall rates of gastrointestinal disorders; respiratory, thoracic, and mediastinal disorders; and nervous system disorders were 10% or more lower with subcutaneous than with intravenous bortezomib, as were the rates of diarrhoea and peripheral sensory neuropathy.

Subcutaneous administration was well tolerated at the site of injection. Nine of 147 (6%) patients had one or more subcutaneous injection-site reaction reported as an adverse event, which resulted in a bortezomib dose modification in two (1%) patients (discontinuation or dose withholding). From the investigator-reported local injection-site questionnaire, the most common reaction was redness (in 84 of 147). Two of 147 (1%) patients in the subcutaneous group had severe injection-site reactions. All reactions resolved completely in a median of 6 days.

Janssen is committed not only to finding new and innovative medicines, but also new ways of delivering those medicines that might be more convenient or better tolerated for patients. By offering a more convenient method of administration and a reduced incidence of peripheral neuropathy, we believe the subcutaneous administration of bortezomib will make a positive difference to patients and to those caring for them.

Source: Janssen