Swedish Orphan Biovitrum has the worldwide rights to this product.
What is Multiferon?
The human genome consists of 13 functional genes that code for interferon-alpha.
Multiferon® is a human multi-subtype leukocyte interferon-alpha consisting of 6 alpha interferon subtypes released by human leucocytes in contrast to recombinant interferon-alpha with only one interferon subtype alpha 2a/b.
The interferon-alpha subtypes are purified from the supernatant of a culture medium of primary human leukocytes challenged with Sendai virus.
Consisting of 6 out of 12 endogenously released alpha interferons Multiferon is similar to naturally occurring alpha interferons in the body. It is highly purified, very effective and well tolerated.
This makes Multiferon® unique and very different to r-IFN.
What is Multiferon used for? Malignant melanoma:
Adjuvant treatment of high-risk patients with cutaneous melanoma, stages IIb-III, after 2 initial cycles of dacarbazine (DTIC).
Other indications:
Treatment of patients who initially respond to recombinant interferon-alpha, but for whom
treatment subsequently fails, most likely as the result of neutralising antibodies.
How is Multiferon used?
Multiferon is administered subcutaneously using a disposable injection syringe.
Dosing of Multiferon®:
Adjuvant treatment of malignant melanoma:
3 million IU three times weekly for 6 months after 2 initial cycles of DTIC 850 mg/m2 (intravenous). DTIC should be administered once every 3 weeks, as well as 3 weeks prior to starting interferon-alpha.
Second-line treatment of viral and malignant diseases:
Clinical experience is limited, but the transition from recombinant interferon-alpha to Multiferon® should not normally entail a change in dosage (IU). Adverse reactions similar to those upon introduction of recombinant interferon-alpha treatment can develop and justify a gradual dosage reduction.
If intolerance persists or recurs after suitable dosage adjustment, Multiferon® treatment should be discontinued. For subcutaneous maintenance treatment, the patient may self-administer the dose at the discretion of the physician. The injection site should be varied during the course of treatment.
How has Multiferon been studied?
In a prospective, controlled, randomized, multicenter study 252 patients with totally resected cutaneous melanoma (248 in stage II_/III and 4 in stage IV) were either treated with two cycles of dacarbazine (DTIC) followed by a 6-month treatment with 3MIU thrice weekly of Multiferon® (n=128; arm A) or received no adjuvant treatment (n = 124; arm B). After a median follow-up of 8.5 years ITT analysis showed that the difference in survival was statistically significant with respect to melanoma-related deaths (HR=0.65, C=0.46-0.97, p=0.022) and close to significance with respect to overall survival (HR 0.71, CI 0.49-1.00, p=0.052). The risk reduction of melanoma associated death, calculated by Cox proportional hazards modeling, after adjusting for identified predictive variables, was almost 50% (p=0,002). The overall efficacy of the treatment appeared to be mainly attributable to effects observed in patients with deep and/or metastasizing tumors (HR 0.60, CI 0.40-0.90, p=0.013)1.
Malignant melanoma - What benefit has Multiferon shown during the studies?
DTIC/Multiferon® so far is the only sequential setting in adjuvant interferon-alpha treatment in patients with malignant melanoma. It further represents the only adjuvant treatment approach for high risk melanoma treatment where low-dose Interferon could significantly increase overall survival in the long-term follow-up. In the high-risk (stage IIb-III) population (n=158) a significant benefit was noted for the patients receiving Multiferon® where 52% were alive at follow up and only 25% in the control group. This difference being highly significant with a p value of 0.008 (HR=0.58). Treatment was well tolerated1.
Multiferon contains:
A variety of subtypes of which some have immunologic effects that are not shared by recombinant IFN-a2 preparation and synergy between various subtypes is known to occur3. This may attribute to the beneficial clinical effect.
Ongoing/Planned Studies:
A neo-adjuvant clinical trial in malignant melanoma is currently in development to confirm efficacy, tolerability and to find biological markers relevant for the biological activity of Multiferon®.
In vitro and in vivo studies are ongoing in different indications.
Side effects:
The most frequently reported were fever, chills, sweating, fatigue, arthralgia, myalgia, headache, anorexia and nausea. Fever and fatigue are dose-related and are reversible within 72 hours of interruption or cessation of treatment.
These acute side effects can ordinarily be alleviated or eliminated by concomitantly administering paracetamol. They tend to subside with continued treatment or dosage adjustment, although ongoing treatment can cause lethargy, weakness and persistent fatigue.
Contents of container:
Each pre-filled syringe contains 3 million IU interferon-alpha per 0.5 ml as a solution for injection, ready for use.
Pack size: 6 x 0.5 ml (0.5 ml = 3 million IU)
Special precautions for storage:
Store in a refrigerator (2°C – 8°C) in the original package in order to protect from light. Do not freeze.
For single use.
Any remaining material must be discarded.
For the purpose of transport or to facilitate use, the product may be kept at room temperature (25oC or below) for up to 2 months. If not used during the 2-month period, it must not be put back in the refrigerator for continued storage. It must be destroyed.
Reference:
1: Stadler R. Acta Oncologica, 2006;45:389-399.
2: Multiferon® SPC.
3: Foster GR, Finter NB. Are all type I interferons equivalent? J Viral Hepatitis 1998;5:143-52.