Ofatumumab

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Articles

Refrigerated Storage

Arzerra · Novartis Pharmaceuticals

Novartis Pharmaceuticals
Arzerra
Concentrate for solution for infusion, 100mg and 1000mg

Contact Novartis in all cases where a deviation from the recommended storage conditions has occurred.

Refer to the current BNF for company contact details.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

13th June 2017
London Medicines Information Service

Lactation Safety Information

Long half-life increases risk of accumulation in breastfed infants
Low levels anticipated in milk due to the drug's properties
Avoid in preterm infants and neonates as large protein molecules may appear in colostrum

New Medicines

Arzerra · Relapsed chronic lymphocytic leukaemia (CLL) - in combination with fludarabine & cyclophosphamide

Information

Arzerra
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Launched
Launched
Launched
December 2016
Yes
Yes
Jan 18 · Novartis has announced withdrawal of ofatumumab for CLL from markets outside the US due to low numbers of patients using the treatment. The company will set up compassionate use programmes so that current patients can continue treatment. Development will continue for refractory NHL and multiple sclerosis [18].
Dec 16 · Licence change approved in EU [17].
Nov 16 · EU positive opinion for a change to the licence to include use in combination with fludarabine and cyclophosphamide for treatment of adults with relapsed CLL [16].
Aug 16 · FDA approves licence extension of ofatumumab to include use with fludarabine and cyclophosphamide for treatment of relapsed chronic lymphocytic leukaemia [15].
Jun 16 · Filed in EU [14].
Mar 16 · Filed in the US [13].
Oct 15 · Filings are now expected to take place in 2016 [12].
Jul 15 · Filings planned for 2015 [11].
Jun 15 · Novartis took over development of GSK oncology products in H1 2015 [10].
Apr 15 · Novartis plans to share COMPLEMENT 2 data with regulatory agencies to assess the potential for future filings [7].
Jun 14 · In view of negative PIII results, GSK & Genmab do not anticipate applying for a licence extension in this specific population [6].
Apr 14 · Ofatumumab has been awarded orphan drug status in the US when used as second-line therapy or greater for CLL [5].
Apr 14 · EU filing will be via the centralised procedure [2].
Nov 08 · Granted orphan designation (EU/3/08/581) by the European Commission for treatment of CLL [3].

Category

Fully humanised, high affinity monoclonal antibody targeted against CD20 cell surface antigen of B-cell membranes
Overall incidence of CLL for all ages is ~ 4.2 per 100,000 per year.
Relapsed chronic lymphocytic leukaemia (CLL) - in combination with fludarabine & cyclophosphamide
Intravenous

Further information

Yes
Suspended

Trial or other data

Jun 15 · Arzerra significantly increased PFS in the PIII COMPLEMENT 2 trial. A combination of ofatumumab, fludarabine and cyclophosphamide increased PFS by 54% compared to therapy with the latter two drugs alone (28.9 months versus 18.8 months, respectively). Also, patients receiving the drug as well as existing CLL treatments had a higher overall response rate (84% vs 68%) than fludarabine and cyclophosphamide alone, and no new safety signals were observed [9].
Apr 15 · COMPLEMENT 2 = NCT00824265 [8].
Apr 15 · Novartis announce top-line results from the PIII COMPLEMENT 2 study showing that treatment with ofatumumab plus fludarabine and cyclophosphamide significantly improved PFS in patients with relapsed CLL versus the latter two drugs alone. Also, the drug’s safety profile seemed consistent with that seen in other trials, with no new safety signals observed [7].
Jun 14 · Ofatumumab fails to meet primary endpoint in PIII study in fludarabine-refractory CLL. There was no statistically significant difference in PFS for ofatumumab vs physician’s choice of treatment - median PFS, as assessed by the Independent Review Committee, was 5.36 months for ofatumumab and 3.61 months for physicians´ choice (Hazard Ratio 0.79, p=0.267) [6].
Apr 14 · PIII NCT00824265 trial is ongoing but no longer recruiting pts [4].
Jul 13 · NCT00824265 is a PIII, open label, randomized trial of ofatumumab added to fludarabine-cyclophosphamide vs. fludarabine-cyclophosphamide combination in 352 subjects with relapsed chronic lymphocytic leukaemia. The primary outcome is progression-free-survival. The study started in Mar 09 and is due to complete Sep 17. Primary outcome data collection Jan 14 [1]

Evidence based evaluations

Arzerra · Relapsing-remitting multiple sclerosis - subcutaneous formulation

Information

Arzerra
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)
Feb 20 · US Food and Drug Administration (FDA) have accepted the company’s Supplemental Biologics License Application for ofatumumab for multiple sclerosis [17].
Feb 20 · Filed in EU via centralised procedure [16].
Oct 19 · Novartis announce plans to file in Q4 2019 [15].
Sep 19 · Novartis plans to file for regulatory approval in the US by the end of the year. Arzerra will carry a different brand name if it’s approved in MS [14].
Dec 18 · Filings still planned for 2019 according to company pipeline [11].
Dec 16 · Filings planned for 2019 [9].
Sep 16 · PIII clinical trials (NCT02792218 and NCT02792231) initiated in the US; estimated primary completion June / July 2019 [7].
Mar 16 · Genmab (originator) reports that Novartis aims to start PIII trials for this indication in the second half of 2016 [6].
Jan 16 · In Aug 15, Novartis said ofatumumab is PIII ready, but to date, PIII studies have not started [4,5]
Aug 15 · Novartis has bought the remaining rights to Arzerra from GSK in a deal worth up to $1 billion; they previously only acquired rights to the drug’s cancer indications. Under the terms of the agreement, Novartis will make an initial payment of $300 million to GSK, with a further $200 million being payable following the start of a PIII study in MS by Novartis. The company may also pay up to $534 million in milestone payments to GSK, who are entitled to royalties of up to 12% of net sales of the drug in autoimmune conditions [4].

Category

Fully humanised, high affinity monoclonal antibody targeted against CD20 cell surface antigen of B-cell membranes
MS usually starts in early adult life; female to male ratio is 3:2. For those with a family history, 4% of people with a first-degree relative will develop the condition [2]. Estimated population in the UK (2012) is about 107,000 with a pronounced northward gradient: prevalence per 100,000 is about 140 in Wales, 165 in England, 174 in N. Ireland and 212 in Scotland.
Relapsing-remitting multiple sclerosis - subcutaneous formulation
Subcutaneous

Further information

Yes
To be confirmed

Trial or other data

Sep 19 · Two identical design, flexible duration (up to 30 months) PIII comparative trials (ASCLEPIOS I and II , NCT02792218 and NCT02792231) met their primary endpoints with ofatumumab demonstrating superiority vs teriflunomide in patients with relapsing forms of multiple sclerosis. Patients on ofatumumab had a reduction in annualised relapse rate (ARR) by 50.5% (0.11 vs. 0.22) and 58.5% (0.10 vs. 0.25) vs teriflunomide (p<0.001). Additionally, ofatumumab showed a relative risk reduction of 34.4% (p=0.002) in 3-month confirmed disability progression and 32.5% (p=0.012) in 6-month confirmed disability progression in pre-specified pooled analyses [13,14].
Dec 18 · Timelines for completion of ASCLEPIOS I & II remain unchanged [12].
Nov 17 · ASCLEPIOS I & II trials are still recruiting and due to complete collection of primary outcome data May 19 [10].
Sep 16 · ASCLEPIOS I trial = NCT02792218; ASCLEPIOS II trial = NCT02792231 [10].
Sep 16 · NCT02792218 and NCT02792231 are double-blind, double-dummy randomised controlled trials of subcutaneous ofatumumab once every four weeks vs. teriflunomide once daily; primary outcome is annualised relapse rate up to 2.5 years. Estimated enrolment is 900 for each study and the estimated primary completion dates are June and July 2019 [7].
Mar 15 · PIII trials expected to begin in 2015 [3].
Oct 13 · Top-line results from P2 study (n=232). Treatment was with 3mg, 30mg or 60mg oftatumumab every 12 weeks, or 60mg every 4 weeks, or placebo followed by 3mg ofatumumab at week 12. The primary objective of the study was to determine whether ofatumumab given subcutaneously reduces the number of new T1-weighted gadolinium-enhancing brain lesions (active brain lesions) over a period of 12 weeks, as compared with placebo, in subjects with RRMS: There was a clear separation from placebo in subjects treated with all doses of ofatumumab compared to subjects treated with placebo [p = 90% reduction in the cumulative number of new T1 gadolinium enhancing lesions for all cumulative doses of ofatumumab >= 30 mg [1].

Evidence based evaluations