 Everything you want to know about Gamunex®.
Remember, your doctor or healthcare provider is the single best source of information regarding you and your health. Please consult your doctor if you have any questions about your health, your symptoms, or your therapy.
Introduction
Clinical Evidence and Indications for Gamunex®
Efficacy
Tolerability
Safety
Reliability
Convenience
Cost/Reimbursement
Introduction
- What is Gamunex®?
- Gamunex, Immune Globulin Intravenous (Human),
10% Caprylate/Chromatography Purified, is an
advanced next-generation IGIV product from Talecris. A convenient, time-saving,
ready-to-use, liquid 10% formulation, Gamunex has
an excellent efficacy, safety, and tolerability profile.1
- Gamunex was the first completely new IGIV product
to be approved by the United States Food and Drug
Administration (FDA) in more than a decade.
back to top
- What makes Gamunex® different from other IGIV products currently on the market?
- The innovative Gamunex production process differs
significantly from traditional IGIV manufacturing
processes, which were based on decades-old technology.
- The Gamunex process results in an improved overall
product profile that better meets patients' needs.
- Key advantages with Gamunex include a high purity
profile; close to physiologic osmolality; no sugar stabilizer;
low sodium concentration; and further
reduced IgA, IgM, and albumin content. In addition,
FDA approval of Gamunex was based on
unprecedented clinical proof of efficacy, tolerability,
and safety.
back to top
- Why is the Gamunex® production process unique and better?
- We started with a clean sheet to design a completely
new manufacturing process, because the old processes
did not provide the flexibility we needed to make
the significant improvements we had in mind for
Gamunex.
- In the past, IGIV product development was simply
based on retrofitting a decades-old process. Our team identified Caprylate/Chromatography
as a gentle, yet very effective and safe, process to
purify Gamunex, resulting in enhanced quality and
reliability of the product supply.
- As part of our continuous commitment, we
built a new, state-of-the-art manufacturing facility
in Clayton, North Carolina-the only facility of
its kind worldwide-that is 100% dedicated to
producing Gamunex.
back to top
- What is Caprylate?
- Caprylate is a naturally occurring fatty acid that
has been proven to effectively, safely, and rapidly
inactivate viruses such as human immunodeficiency
(HIV-1), West Nile, SARS, hepatitis B (HBV),
and hepatitis C (HCV).
- The Caprylate viral inactivation process is gentler
than previous processes; it preserves the biological
activity of the fragile immunoglobulin proteins and
translates into a safe and effective product. Although
new to IGIV, caprylate has been used for more than
50 years as a stabilizer for human albumin.2
back to top
- Why did Talecris substitute solvent/detergent (S/D) with Caprylate in the new production process for Gamunex®?
- Using Caprylate was part of an overall redesign and
optimization of the Gamunex production process.
- Caprylate, a naturally occurring substance, is used
instead of solvent/detergent, because it inactivates
viruses in a significantly shorter period of time and is
also gentler on the fragile immunoglobulin proteins.
This results in improved protein integrity and higher
purity which, in turn, may translate into better efficacy
and tolerability
- New to IGIV, caprylate has been used for more than
50 years as a stabilizer for human albumin.2
back to top
- How does the Caprylate/Chromatography process improve product purity and reliability of supply?
- In IGIV, the manufacturing process ultimately
determines the quality of the final product. Talecris'
innovative process includes breakthrough purification
steps using Caprylate/Chromatography, a more
gentle approach than the S/D methods used in
previous-generation IGIV products.
- This gentler process gives Gamunex, Immune
Globulin Intravenous (Human), 10% Caprylate/
Chromatography Purified, greater protein integrity and
enhanced purity, which results in an excellent product
profile: effectiveness in infection prophylaxis (eg, for
primary humoral immunodeficiency [PI] patients and
in diseases such as idiopathic thrombocytopenic
purpura [ITP] requiring immune system modulation),
as well as excellent tolerability.1
- Because the process is much shorter and fully integrated,
reliability of supply also has been improved.
back to top
- How was Gamunex® tested before the FDA approved it?
- Before FDA approval of Gamunex, we conducted
the largest clinical trials program ever performed for
the licensure of an IGIV product.
- The results demonstrated the significant benefits
of Gamunex, including its excellent efficacy, safety,
and tolerability profile.
- The robust clinical data for Gamunex demonstrate
that different production methods might lead to
different clinical outcomes, as Gamunex showed
surprising positive differences in the trials compared
with Gamimune N, 10%, Immune Globulin
Intravenous (Human).2
back to top
Clinical evidence and indications for Gamunex®
- What clinical trials were performed with Gamunex®?
- The trials supporting licensure of Gamunex were
unprecedented in many ways. No clinical trials of
this size and design have ever been performed in
IGIV history.
- We conducted the first licensure-relevant, randomized,
double-blind, controlled, statistically powered,
head-to-head therapeutic equivalence IGIV trials for
PI and ITP. The trial program included 7 trials and
more than 350 patients2:
2 pharmacokinetic trials, 4 efficacy and tolerability trials, 1 rapid-infusion trial.
- The Gamunex studies have provided unprecedented
proof of efficacy, safety, and tolerability. Gamimune
N, 10%, Immune Globulin Intravenous (Human),
a market leader in the United States, was the comparator
in many of these trials.
- The trials were designed to demonstrate that
Gamunex is at least as effective, well-tolerated, and
safe as Gamimune N, 10%, but the results showed a
consistent trend toward better efficacy for Gamunex.2
back to top
- What is Gamunex® approved for in the United States?
- In the United States, Gamunex is indicated as
replacement therapy for PI disorders in which impairment
of antibody-forming capacity has been shown,
such as congenital agammaglobulinemia, a common
variable immunodeficiency; X-linked immunodeficiency
with hyper IgM; Wiskott-Aldrich syndrome;
and severe combined immunodeficiencies.1
- Gamunex also is indicated in ITP to rapidly raise
platelet counts to prevent bleeding or allow a patient
with ITP to undergo surgery.1
back to top
Efficacy
- How do the Gamunex® clinical evidence findings compare with those of Gamimune® N, 10%?
- Based on an unprecedented, randomized, double- blind, comparative, therapeutic-equivalence clinical trial program versus Gamimune® N, 10%, Gamunex® presents exceptional clinical proof of an IGIV product's efficacy and tolerability.
- Gamunex® is at least as efficacious as Gamimune® N, 10%.
- Gamunex® demonstrated a consistent trend (in part, statistically significant) of enhanced efficacy in both primary humoral immunodeficiency (PI) and idiopathic thrombocytopenic purpura (ITP).1
back to top
- Are all IGIVs equally effective?
- No. As with all biological products, the manufacturing
process defines the product profile. Because each IGIV
product is manufactured differently, the effectiveness
and tolerability of each IGIV may be different as well.
- The Gamunex trial program, for the first time,
provides evidence that different manufacturing
methods may result in different clinical outcomes.
- In addition, a recent patient survey by the Immune
Deficiency Foundation confirmed that patients
perceive differences between IGIV products, such
as differences in product effectiveness (efficacy) and
tolerability (side effects).
back to top
Tolerability
- How well is Gamunex® tolerated?
- Gamunex provides excellent tolerability.1 The PI trial
for Gamunex reported a low incidence of adverse
events.3
- The trial results further showed Gamunex is
well tolerated even at the higher doses required
for ITP therapy.1
- The most common side effects noted during the clinical
trials included headache, vomiting, fever, nausea,
rash, and back pain. More than 90% of those adverse
events were mild to moderate and transient. No serious
adverse events such as thromboembolic events, renal
failure, decreased cardiac output, or aseptic meningitis
were observed during the trial.
back to top
- Were serious adverse events observed in the licensure-relevant trial program?
- Previous reports with IGIV products grouped as a
class have indicated an increasing incidence (up to
5%) of serious adverse events associated with IGIV
therapy.4
- However, under the highly controlled conditions
of the Gamunex trial program involving more
than 2000 doses administered to more than 350
patients-testing its tolerability in anti-infective
and immunomodulatory diseases over a wide range
of dosing regimens-no serious adverse events, such
as thromboembolic events, renal failure, decreased
cardiac output, or aseptic meningitis, were observed.
back to top
- Is Gamunex® safe for IgA-deficient patients?
- Individuals with severe, selective IgA deficiencies
(serum IgA <0.05 g/L) who have known antibody
against IgA (anti-IgA antibody) should only receive
Gamunex with utmost cautionary measures due
to the risk of severe immediate hypersensitivity
reactions, including anaphylaxis.5
- No experience is available on tolerability of
Gamunex in subjects with selective IgA deficiency,
since they were excluded from participation in the
clinical trials with Gamunex.
back to top
- Is Gamunex® safe for patients with diabetes, renal disease, or decreased cardiac output? How well is Gamunex® suited for children or elderly patients?
- The composition of an IGIV product may affect tolerability.
Each step in the manufacturing process
provides an opportunity to introduce product differences,
resulting in different product composition.
Consequently, currently available IGIVs vary in
terms of osmolality, sodium concentration, and sugar
content, as well as product formulation and concentration.
The knowledge of differences in product features
may be important for patients with certain risk
factors. For example, in patients with decreased cardiac
output, vascular disease, or renal dysfunction, as
well as neonatal patients or the elderly, fluid volume
may be an issue.
- Therefore, the use of a product formulated at a 10%
concentration will reduce the infused volume by one
half compared with a 5% concentrated product.
Gamunex is a volume-saving, 10%, ready-to-use liquid
formulation available in the United States.1
Clinical considerations for fluid-restricted
patients (patients with decreased cardiac
output, young children, or elderly patients):
Gamunex is a 10% concentration, which
translates into half the fluid volume of
standard 5% IGIV products.1
- Sodium concentration also varies widely in IGIV
preparations. Concerns have been raised about the
possible association of increased sodium concentration
and significant adverse events, including thromboembolic
events. Reconstituting certain lyophilized
products to higher concentrations may lead to excess
sodium concentrations (up to ~2%).6
- Another important product feature is osmolality.
Reconstituting lyophilized products to a higher
concentration to reduce volume load may lead to
an osmolality that exceeds the physiologic range of
285 mOsm/kg to 295 mOsm/kg. IGIV solutions
with osmolalities that significantly exceed the physiologic
range may contribute to the risk for development
of an adverse event, such as a renal event or
thromboembolic complication.6
Clinical considerations for patients at risk
for thromboembolic events: Gamunex
has a close to physiologic osmolality of
258 mOsm/kg and contains only trace
amounts of sodium.1
- The addition of sugar to IGIV products as a stabilizer
to prevent IgG aggregate formation is thought to
be a cause of some serious adverse events. In compiled
reports of episodes of renal failure in response
to IGIV, 90% were attributed to products containing
sucrose, and 8% to glucose- or maltose-containing
products.7
- Gamunex is sugar-free. Because Gamunex is formulated
at a low pH, which prevents aggregate formation,
there is no need for the inclusion of an additional
sugar stabilizer.1
Clinical considerations for pre-/diabetics
or patients with renal disease: Gamunex
contains no sugar. Glycine, an amino acid,
is used as a stabilizer.1
- Patients should be aware of the diverse features of each
IGIV product in relation to their own risk profile to
minimize the risk of IGIV-related adverse events.
- It is important to understand many patients may fall
into more than 1 risk category with regard to the
development of adverse events. Therefore, the
combination of product features must be carefully
considered to identify the IGIV that is the most
appropriate match for the individual patient.
back to top
- Are there any drug interactions with Gamunex®?
- Antibodies in Gamunex, Immune Globulin
Intravenous (Human), 10% Caprylate/
Chromatography Purified, may interfere with the
response to live virus vaccines, such as measles,
mumps, and rubella. Therefore, use of such vaccines
should be deferred until approximately 6 months
after Gamunex administration.1
back to top
- Is Gamunex® compatible with other IV solutions?
- Gamunex is not compatible with saline. If dilution is
required, Gamunex may be diluted with 5%
dextrose in water (D5/W).1
back to top
Safety
- Is Gamunex safe?
- Yes, Gamunex is safe. The demonstration of a
plasma-derived product's viral safety is an important
precondition to gaining regulatory approval from
agencies such as the US FDA, the Canadian Health
Authority, and the Paul Ehrlich Institute in
Germany.2
- In fact, the Gamunex production process is based on
a new safety paradigm that increases the margin of
pathogen safety. By starting from scratch, our
scientists had a unique opportunity to combine
purification, stabilization, and viral inactivation and
removal procedures into a single integrated process,
shortening the production time by over 60%. We
introduced Caprylate, which inactivates viruses in a
significantly shorter period of time than solvent/
detergent treatment. The result is a well-balanced
combination of 2 viral inactivation and 3 viral
removal steps, as well as 2 prion removal steps. And
we went one step further by ensuring these steps
are mechanistically different, therefore increasing the
likelihood that the widest possible range of
pathogens-including those as yet unknown-is
eliminated during Gamunex production. In addition,
the Gamunex process has been tested for its robustness.
Pathogen inactivation is tested beyond the established
range of manufacturing parameters to ensure
that variations in any of these processing parameters
do not affect the levels of pathogen reduction.2
back to top
- How has the Gamunex viral elimination program
been tested?
- We have introduced a new paradigm in safety
evaluation to assess the viral reduction capacity
of its Gamunex process. It has 3 cornerstones2:
-Fast and very effective viral inactivation with
caprylate
-Robustness testing of all relevant safety steps
(with its effectiveness validated outside normal
production range)
-Assessment of mechanistic independence of viral
reduction steps
back to top
- Where does Talecris get the plasma used for its production
of Gamunex?
- Talecris uses only plasma collected from donors at
FDA-licensed facilities in the United States.2
back to top
- What tests are performed before plasma is processed at
Talecris' manufacturing site in Clayton, North Carolina?
- Talecris performs extensive screening and testing
of donors, as well as applies inventory hold and
look-back.
- All plasma is tested for HIV-1 and HIV-2, HBV,
and HCV. Talecris incorporates nucleic
acid testing/polymerase chain reaction (NAT/PCR)
testing for HIV, HBV, HCV, and Parvovirus B19.2
back to top
- Has Gamunex been tested against new and emerging
viruses, such as SARS and West Nile?
- Talecris Biotherapeutics has confirmed its plasma collection and manufacturing processes have been shown to significantly remove and/or inactivate enveloped viruses, including West Nile virus. Since the caprylate and low pH portions of the Gamunex manufacturing process have been shown to inactivate every enveloped virus tested thus far, there is reasonable assurance that the agent that causes SARS (an enveloped virus) would be inactivated as well.2
back to top
- What safety steps are implemented in the manufacturing
process to eliminate potential viruses and prions in the
source plasma?
- The Gamunex manufacturing process incorporates 2 separate virus inactivation steps and 3 virus removal steps.
- The Gamunex Process, Talecris' new Caprylate/ Chromatography-based production process, also has been carefully evaluated for its prion removal capacity.2 The Gamunex manufacturing process incorporates 2 prion removal steps.
back to top
- How safe is Gamunex from prions (suspected cause of
mad cow disease)?
- Talecris has performed extensive evaluations and significant
data has been generated, demonstrating the ability
of the Gamunex manufacturing process to remove
prions. As with any plasma-derived product, Gamunex
theoretically carries the risk of transmitting
prions/transmissible spongiform encephalopathy
(TSE) agents (Creutzfeldt-Jakob disease). Because of
their resistance to typical methods of pathogen inactivation,
the reduction of prions/TSE agents in a
manufacturing process presents a unique challenge. The Gamunex package insert states that several of the individual production steps in the Gamunex manufacturing process have been shown to decrease TSE infectivity of an experimental model agent. These studies provide reasonable assurance that low levels of TSE agent infectivity, if present in the starting material, would be removed.
back to top
- What is Talecris doing about the potential for
product tampering?
- Responding to recent concerns about product tampering
of intravenous products, Gamunex is the only
product that utilizes shrink-banding for enhanced
tamper-evident packaging.2
- The shrink-band is designed as a clear plastic wrap,
imprinted with the company logo, covering the neck
and lid of the bottle. The shrink-band comes with a
pull-tab for easy removal. If tampering has occurred,
the shrink-band will be broken or loosened, and the
disruption will be obvious to the naked eye. If a disruption
in packaging is identified, the product
should not be opened or used.2
back to top
Reliability
- Will supply be an issue for Gamunex®?
- Consistent and reliable supply of this lifesaving therapy is of utmost importance. Talecris has addressed this issue with a variety of measures and investments:
- We built a totally new, dedicated production facility for the manufacture of Gamunex®, a facility that meets or exceeds current Good Manufacturing Practices (cGMP) standards.
- We developed a new production process, caprylate/chromatography-based Gamunex® Process, that is easier to manage and minimizes the complexity and related trade-offs of current industry standards in IGIV production.
- All production equipment in the new facility is dedicated to Gamunex® production.
- Two separate production lines for Gamunex® ensure a consistent supply.
- The facility is fully automated to reduce the potential for operator error and to maintain batch-to-batch consistency.
back to top
Convenience
- What concentration is Gamunex®?
- Gamunex is a volume-saving, 10%, ready-to-use, liquid
formulation.1
back to top
- What are the storage conditions for Gamunex?
- Gamunex offers a long shelf life. Product may be stored for 36 months at 2°C to 8°C (36°F–46°F), and product may be stored at temperatures not to exceed 25°C (77°F) for up to 6 months anytime during the 36-month shelf life, after which the product must be immediately used or discarded. Do not freeze. Do not use after expiration date.1
back to top
- What is the recommended infusion rate
of Gamunex?
- Gamunex should be infused at an initial rate of 0.01
mL/kg/min (1 mg/kg/min) for the first 30 minutes.
If well tolerated, the rate may be gradually increased
to a maximum of 0.08 mL/kg/min (8 mg/kg/min).1
back to top
- How does the overall infusion time of
Gamunex compare with other brands?
- The overall infusion time is defined by its concentration
and maximum labeled infusion rate. Gamunex
compares very favorably through its combination
of a fast infusion rate (up to 0.08 mL/kg/min) and
its 10% formulation.1
- But this Gamunex convenience advantage does not
come at the cost of excess osmolality or high sodium
concentration, which may lead to an increase in adverse
events, as seen when some lyophilized products are
dissolved with less diluent to make a more highly
concentrated product.8
- The Gamunex clinical trials have demonstrated excellent
tolerability at any infusion rate up to
0.08 mL/kg/min.1
back to top
Cost/Reimbursement
- What reimbursement support does Talecris, manufacturer of Gamunex, provide?
- To ensure access and reimbursement for most
patients, Talecris is working with third-party payers,
such as Medicare, Medicaid, the Federal Supply
Schedule (FSS), insurance carriers, and others.
- Please review the reimbursement information on this website and consult your specific insurance carrier
to determine the status of reimbursement for
Gamunex, Immune Globulin Intravenous (Human),
10% Caprylate/Chromatography Purified.
- If you have additional questions related to reimbursement
or need reimbursement support, please contact
our Reimbursement Helpline at 1-877-TBR EIMB (827-3462)
back to top
Remember, your doctor or healthcare provider is the single best source of information regarding you and your health. Please consult your doctor or healthcare provider if you have any questions about your health, your symptoms, or your therapy.
†Gamimune N 10%, Immune Globulin Intravenous (Human)
Please contact us for more information or with any specific questions you may have.
Please see full Prescribing Information including boxed WARNING.
References
- Gamunex full Prescribing Information.
- Data on file, Talecris Biotherapeutics.
- Roifman CM, Schroeder H, Berger M, et al. Comparison of the efficacy
of IGIV-C, 10% (Caprylate/Chromatography) and IGIV-SD,
10% as replacement therapy in primary immune deficiency. A randomized
double-blind trial. Int Immunopharmacol. 2003;3:1325-1333.
- Nydegger UE, Sturzenegger M. Adverse effects of intravenous
immunoglobulin therapy. Drug Saf. 1999;21:171-185.
- Ballow M. Intravenous immunoglobulins: clinical experience and
viral safety. J Am Pharm Assoc. 2002;42:449-459.
- Gelfand E, Goldsmith J, Lederman H, Primary Humoral
Immunodeficiency: Optimizing IgG Replacement Therapy, IDF
Clinical Focus, October 2003, Issue 11.
- Renal insufficiency and failure associated with immune globulin
intravenous therapy-United States, 1985-1998. MMWR Morb
Mortal Wkly Rep. 1999;48:518-521.
- Siegel J. Intravenous immune globulins: therapeutic, pharmaceutical,
and cost considerations. Pharm Pract News. 2001;28:11-13.
©2006 Talecris Biotherapeutics
|
