Xolair Literature Review - Dissertation Example

?Xolair – Literature Review Introduction: Xolair is the trade of omalizumab which is one of the selected humanized antibody drugs used primarily for the treatment of patients with moderate to severe allergic asthma associated with them. Under the trade name of Xolair, it is known as an additional therapy aimed to improve control over severe allergic asthma and other associated problems (including those ranging from vitro reactivity and reduced lung functioning to perennial aeroallergen) within patients of various ages (Rosenwasser, 2003). The intensity, chemical properties, action mechanisms, and associated with omalizumab are all pre-generalized; however, they are controlled at the time of its manufacturing when done under the label of Xolair, and involve few specific dimensions to be identified. Further, understanding its production procedure in the raw-to-commercial forms contributes greatly towards building a theoretical relationship between its positive and negative impacts (“Xolair Fact Sheet”, 2011). Therefore, this review initiates by opening a succinct discussion regarding its origins and chemical features, which is followed by a detailed description of its production, purification, and commercialization phases. After this, some pros and cons associated with the drug are discussed, along with some secondary clinical trials that shed light on its efficacy in different age groups and dosage formulations. In the final sections of this review, a brief list of general precautions and pre-defined pharmacokinetic properties are also added to not to leave some important aspects untouched. Therefore, the reader of this review is suggested to make a close reading in order to explore relationship between different dimensions of Xolair. 2. Origins: It has been known that asthma is a type of chronic inflammatory disorder which is adapted by the patient from his or her surrounding environment. In most cases of asthmatic patients, the disease prevails almost unnoticeably and its initial phases reflects an allergic component which ultimately results in the exceeded production of immunoglobulin E (lgE) against the several environmental allergens like pollen, dust particles, wood crush, sand nits, etc. Furthermore, the produced lgE makes a bond with receptors of patient’s cellular membrane and as a reaction produce inflammatory mediators from within (“Scientific Discussion-Zolair”, n.d.). In this type of reaction, an anti-lgE is supposed to restrict the creation of bond between lgE and cell membrane receptors, in order to reduce the release of inflammatory mediators (Miller et al., 2008). It happened in 1987 at Houston, Texas, that scientists of a local pharmaceutical firm (Tenox) carefully studied the phenomenon of asthma prevalence, and came up with a laboratory prototype of an anti-lgE, which until the year 1991 was unable to get international exposure. However, in the late 1990’s, controlled clinical trials were conducted over patients with mild and severe paediatric and allergic rhinitis by the collaboration of different international pharmaceutical firms, and from the year 1996, omalizumab was made available publicly under the trade name of Xolair by different pharmaceutical firms as one of the most effective allergic asthma treatment drug, referred commonly as anti-lgE. However, despite several clinical trials and experiments over the commercial product of Xolair (and its composing omalizumab), there are still researches and developments which are being conducted in order to verify all the observable effects in different cases of asthma (“Tanox, Inc. – 2010 Company Profile”, 2010). 3. Drug Description: Xolair (or omalizumab) can be terminologically described as a monoclonal anti-body derived from recombinant chromosome (based over lG1k) which impasses particularly to mammal immunoglobulin E (or lgE). Further, its pharmacodynamics reveals that it constrains the association of lgE with cellular membrane receptors (specifically FC3Rl) over the surface of mast cells and basophils (“Omalizumab”, 2011; Rosenwasser, 2003). In DrugBank’s article, “Omalizumab”, the common properties of Xolair (or Omalizumab) are presented: a. Protein Chemical Formula: C6450H9916N1714O2023S38 b. Protein Structure: c. Drug Category: Immunomodulatory/anti-asthmatic agent d. Distribution Volume: 78 ± 32 mL/kg e. Melting Point & State: 61-71°C, liquid 4. Production Processes: Xolair can be taken as a form of glycosylated monoclonal antibody, in which the active constituent of omalizumab is represented by mammalian cells, and thus, its molecule is generated through a long fermentation process in huge bioreactors (“Omalizumab”, 2011). These cells are frequently harvested from the ovarian cells of Chinese hamsters (Rosenwasser, 2003; “Scientific Discussion- Zolair”, n.d.). This process of fermentation involves induction of energy from the oxidation procedure of multitude of organic compounds (like proteins or carbohydrates) with the help of an endogenous electron-accepting entity, which usually is an organic compound. After the process of fermentation, the obtained omalizumab complex is purified by counteractive chromatographic procedures, and ultimately, is concentrated through paired ultra-filtration mechanism. This concentration yields a product which after successive trials is commonly commercialized under the trade name of Xolair (“Omalizumab”, 2011). The above mentioned specifics of production of omalizumab as Xolair are presented below: 4.1. Drug Development: The development of omalizumab is carried out in a batch fed suspension cell culture, which is a three step process: 1. Seed Train Step: Within this step, a continued provision of mammalian cells is made under a specific pressurized environment through the seed train. 2. Inoculum Train Step: Within this step, the cell population is expanded by the provision of inoculum train, in order to introduce it into the production culture. 3. Production Step: In this step, the chemical product is obtained (“Scientific Discussion- Xolair”, n.d.). In order to provide the seed train, a container or vessel from the preserved cell bank is defrosted and the culture is extended under selective pressure within the bioreactors. With this, an incessant process of continuous sub-cultivation of cells is used to maintain the seed train (within a selective medium). To provide inocula for omalizumab production cultures, a portion of the seed train cell population is expanded by serial subcultivations using non-selective medium in stainless steel bioreactors of increasing volumes. The manufacturing culture is initiated by transporting cells into a bioreactor holding non selective and serum free production medium. Other acute parameters are managed and regulated during the entire cell culture processing procedure, and collective media to be inducted are passed through a sterile filter of dimensions less than 0.22?m. Through this, several production groups are imitated from a single seed train, and subsequent to the production procedure, the culture fluid having omalizumab is alienated from the cells by centrifugation. Also, at this stage, it can be be held refrigerated before the purification for a pre-defined period that is vindicated adequately by assessing the state of culture (“Scientific Discussions- Xolair”, n.d.). 4.2. Drug Purification: The purification procedure of Xolair as omalizumab consists of three significant chromatographic stages. The first stage employs immobilised protein-A attraction based chromatography; the second one presents cation (negative) exchange chromatography; and the third stage comprises of anion (positive) exchange chromatography. The obtained solution from this process of chromatographic elution is concentrated further by subsequent filtration procedures, and the yielded produce is taken as the substance for storage. For storage purposes, the omalizumab formulated drug substance is filtered (through the same 0.22?m sterile filter) and packed into massive stainless-steel tanks, which are usually aimed to make the storage and transportation procedures longer and compatible enough to cope at extremely low temperatures, that is, less than -10°C. More specifically stating, the yielded purified drug is stored at temperatures ranging from -10°C to -20°C until further procedures of finished commercialized product are taken out (“Omalizumab”, 2011; “Xolair Fact Sheet”, 2011). 4.3. Commercial Finalizations: As a commercial product for asthma treatment, omalizumab is produced in the form of a sterilized lyophilised precipitate (or powder), which is what we call Xolair. The omalizumab stored as bulk under the above mentioned temperatures is in the form of liquid solution which is filtered at 0.2?m into a steam-sterilised filling tank. Then under sterilized conditions, this solution is packed by weight into sterile and depyrogenated 5ml vials and moderately stoppered with lyophilisation corks. These vials are lyophilised following a cycle of controlled conditions of temperature, pressure, and time. After the completion of lyophilisation cycle, the solution is turned into a fine powder, and the vial corks are fully seated under nitrogen in the sterile chamber and are then removed for capping purposes. This marks the completion of a single batch of lyophilised solution of omalizumab, ready for commercial uses. In the meantime, the approval limits of the manufactured batches are used to monitor critical values involved in the process of drug development, and each and every unit is analysed and evaluated for its stability and reactiveness (“Omalizumab”, 2011; Rosenwasser, 2003).. This process is almost as is employed by different commercial drug manufacturers who commercialize omalizumab either as Xolair or as any other product related to the treatment of asthma. Furthermore, this procedure is considered to be highly intricate as the mechanism needed for its core process automation and engineering is extremely complex, and for this reason, there are very few manufacturers which actually produce this drug on commercial basis. Also, since the manufacturing procedure is high-tech as well as complex, therefore, the cost of Xolair is relatively higher than other anti-lgE compounds (Smith et al., 2008). 4.4. Product Specifications: The product specifications for Xolair are sufficiently vindicated as maximum of the critical procedures used for drug analysis are identical to the norms of pharmaceutical industry. More specifically, the effectiveness, strength, and concentration of Xolair are kept parallel to the common drug substance-test approaches. Further, there is only a single manufacturer to which product name Xolair is patented, and that is Genentech, Inc. A subsidiary of this pharmaceutical firm named as Genentech Vacaville also produces and distributes omalizumab under the product name of Xolair. Both of these manufacturing sites develop Xolair in two basic formulations for commercial purposes i.e. 75mg and 150 mg. The fundamental products specifications of both formulations indicate that the batch-to-batch consistency of manufacturing process succinctly presented above are in accord with the conventional procedures of drug substance analysis (“Xolair Fact Sheet”, 2011). 5. Registration: Xolair (or omalizumab) has been registered and permitted by United States Food & Drug Administration (FDA) for applications on adults, and on children around 12 years of age and older, who possess mild or extreme persistent asthmatic conditions, or have a positive skin test revealed, or are in vitro reactivity to a perennial aeroallergen, or affected by the usage of steroids in associated conditions (“Xolair (omalizumab)”, 2011). 5.1. Treatment/Application Guidelines: As mentioned before, the application of Xolair (omalizumab) is proved to be medically necessary for the treatment of moderate to severe asthma related to allergies (in all ages over 12 years), whose indicators are not sufficiently eliminated by steroids. Further, “Xolair (omalizumab)” indicates that the intended applicator must fulfil all of the following conditional criteria in order to have Xolair used as a treatment: 1. Should be aged above or around 12 years. 2. Should have a positive skin test reaction to perennial aeroallergen. 3. Should have such levels of asthmatic conditions which are out of steroidal controls (2011). 6. Global Sales: This data regarding the global sales of Xolair is taken as-is from Genentech’s web archives: Xolair Sales – USD Million Year Q1 Q2 Q3 Q4 Year Total 2008 $ 117 $ 129 $ 136 $ 135 $ 517 2007 $ 111 $ 120 $ 121 $ 120 $ 472 2006 $ 96 $ 106 $ 108 $ 117 $ 428 2005 $ 68.6 $ 82.1 $ 81.4 $ 95.5 $ 327.6 2004 $ 30.0 $ 43.7 $ 53.9 $ 60.9 $ 188.5 2003 - - $6.8 $ 18.5 $ 25.3 Source: (“Xolair Historical Sales Facts”, 2011) 7. Action Mechanisms: The basic action mechanism of Xolair is identified as its activity of binding the IgE to the highly identical IgE receptor, i.e., Fc&RI, over the exterior of mast cells and basophils. It causes decline in surface bound IgE on Fc&RI bearing cells, which limits the degree of release of mediators of the allergic response. Further, the treatment with Xolair also decreases the amount of Fc&RI receptors on basophils in certain atopic patients. Actually, omalizumab is considered to limit the set of free IgE existing to interrelate with effector-cells and to diminish the ensuing allergic reactions in atopic patients. Through this, omalizumab also constitutes complexes of limited size with IgE and thus decreases the free IgE levels within (Miller et al., 2008). In some cases, omalizumab can intrude within the allergic cascades by either developing complexes with IgE to avoid the build-up of effector cells, or by assisting off-loading of mast cells and basophils by catching IgE as it dissociates from the receptor, or simply by demodulating Fc&RI as a thru-reaction of the decrease in open IgE levels (Smith et al., 2008). 7.1. Associated Benefits: The essential clinical trials of Xolair as an add-on therapy in patients with allergic asthma; specifically those who have on-going symptoms (despite the use of moderate to high-dose inhaled steroids and bronchodilators), verified a comparative decrease of 48% to 58% in the number of protocol?defined asthma exacerbations per patient. Further, patients treated with Xolair are found to be able to attain superior drops in steroid dose usages i.e. 75% to 83% dose reduction, with even greater number of asthma affected patients treated with Xolair being able to completely discontinue steroid uses, which are common in asthmatic diseases. Moreover, enhancements in these endpoints are not at the cost of additional rescue medication use – an indication that rescue medication is significantly reduced in patients who are treated with Xolair (Rosenwasser, 2003). Also, few verifiable and supportive clinical trials of Xolair establish that in asthmatic patients, reliant on on extraordinary dosage of inhaled-steroids, the treatment with omalizumab-based Xolair permitted for a significant reduction in inhaled-steroid use without an increase in asthmatic exacerbations. Finally, in patients with excessively persistent asthmatic symptoms, the subsequent doses of Xolair caused a 61% reduction in the base rate of clinically significant asthma exacerbations over the period of 12 months (“Xolair Fact Sheet”, 2011). 7.2. Associated Side Effects: Almost all the clinical trials that have been conducted to date suggest that Xolair should always be introduced under the presence of an expert, since a highly dangerous allergic reaction known as anaphylaxis has had happened in some cases of asthmatic patients being treated with Xolair (“Xolair Fact Sheet”, 2011; Miller et al., 2008). The anaphylaxis is referred as a life threatening condition, which ultimately can lead to patient’s death as well if caused on higher intensities. More specifically, it has been observed that signs of breathlessness, excessive coughing, chest-tension or discontinued breathing, extremely low blood pressure, faintness, rapid/weak heart-beating activity, nervous anxiety, or feeling of depression right after the application of Xolair are associated symptoms of various intensities of anaphylaxis (Miller et al., 2008). Furthermore, some other side effects associated with persistent usage of Xolair include reddening and itching of skin, feeling of warm skin, minor swelling on throat or tongue along with gullet stiffness, change in voice tone, and trouble swallowing food items. It is also to be mentioned here that these symptoms or side effects have no particular timing found to be associated with them for their appearance, and it could take several hours or just few minutes to have these side effects become observable by the patient (“Xolair Fact Sheet”, 2011). 8. Reflections from Specific Clinical Trials: 8.1. Allergic Asthma: The prime target of Xolair is conventionally thought (and proved to be) the allergic asthma, and its different forms in patients of different ages (D’Amato et al., 2004). For this reason, a study conducted a trial over 1136 patients ranging from 12 to 76 years of age, and all of them were randomized to receive either subcutaneous placebo or omalizumab-based Xolair every two to four week period (Busse et al., 2001). More specifically, the Xolair doses were centred on body weight and on zero IgE levels. The yielded results showed that around 542 patients (86%-88%) experienced no asthmatic exacerbations in the allocated period, in contrast to 70%-77% of placebo fed patients in the stable-steroid stage. Further, during the 12-week steroid-taper phase, some 79% to 84% of Xolair patients had no exacerbations in comparison to 68% of placebo treated patients. Furthermore, another study based on conducting the clinical trial of Xolair over allergic asthmatic patients below 12 years of age obtained that it had comparably effective results for children as well, in contrast to those children who were treated over steroids (Cowen et al., 2009). 8.2. Occasional Allergic Rhinitis: In order to assess the efficacy of Xolair for occasional or seasonal allergic rhinitis, a study assessed some 536 patients aging between 12 and 75 years with a scalar threshold of 2 year disease history lying under mild or extreme seasonal allergic rhinitis. At this point, the mild to extreme symptoms of occasional allergic rhinitis can be defined as a condition of a patient having sneezing, itchiness, running or stuffy nose, wet or reddened eyes, and itchy throat (Chervinsky, 2003). In this manner, 137 patients were randomly assigned to receive Xolair’s 150 mg formulation, 129 were assigned to receive 75 mg formulation, while 136 randomly received placebo hypodermically just before their usual season of allergy. The primary efficacy endpoint was the average daily nasal symptom severity score ranging between 0 and 3. The obtained results showed that nasal symptom severity scores were significantly lower in patients who had 150 mg of Xolair, than in those who received placebo i.e. 75% than 98%, respectively. Further, a significant relationship was witnessed between IgE level drop and nasal symptoms (“Xolair (omazimuab)”, 2011). Also, rhinitis specific feature of scores were steadily superior in patients who received 150 mg of Xolair, as compared to those who had 75 mg dosage or had placebo, and this pattern did not fall in the top allergy season. Although, it was also additionally found that the large placebo effect makes the true effect of Xolair in treating seasonal allergic rhinitis, which is quite difficult to determine in terms of statistics (Corren et al., 2004). 8.3. Perennial Allergic Rhinitis: A study aimed to identify the efficacy, safety, and tolerability of Xolair in the limited treatment of patients with perennial allergic rhinitis with moderate to severe symptoms in a randomized, double-blind trial identified that patients in the group having Xolair had a 69% reduction in the average daily nasal severity in contrast to 49% of the placebo treated patients. Furthermore, some symptoms associated with PAR were controlled in this activity in 28% of the studied patients in the Xolair group, as compared to the10% of patients in the placebo-treated group. Moreover, in both study groups, Xolair significantly reduced anti-histamine usage per month, in comparison with placebo. However, the study also concluded that some large scale studies are required to confirm the results of these limited trials, which were conducted over a relatively smaller number of patients (Heil et al., 2010). 8.4. Type-I Hypersensitivity: A study employed a randomized trial that assessed 84 patients with a history of immediate hypersensitivity to peanut. The anti-IgE humanized monoclonal antibody in doses of less-than-equal to 150mg or placebo were given hypodermically every four weeks for four doses, with a food challenge given two to four weeks after the last dose. The anti-IgE significantly increased the oral-food-challenge threshold versus placebo. It was also obtained within the screening period that, some patients underwent a double-blind oral food challenge with either peanut flour or wheat flour, while patients who reacted to less than or equal to 150 mg of peanut flour and not wheat flour were found to be randomized to Xolair or placebo for 20-22 weeks (Smith et al., 2008). 8.5. Chronic Urticaria: Chronic idiopathic urticaria has an autoimmune-basis, and is usually triggered by flowing antibodies alongside the highly attractive IgE receptors (Fc&R1) most commonly, and less commonly against IgE. Therefore, for this particular reason, the medical literature also reports successful treatment of chronic urticarial patients with omalizumab or Xolair (Smith et al., 2008). 8.6. Atopic Dermatitis: There are several reports on anti-IgE therapy in patients with atopic eczema and although some describe favourable treatment results, and these are not consistently reported in all studies (“Xolair Fact Sheet”, 2011; D’Amato et al., 2004; “Xolair (omazimuab)”, 2011). 9. Patient’s Safety Precautions: a. As mentioned earlier that Xolair can cause anaphylaxis as its side effect upon excessive usage, and hence, patient’s associates and doctors should always lookout the patient for some time in private for symptoms of anaphylaxis after treating with Xolair. Also, if patients have signs or symptoms of anaphylaxis, they should immediately tell their doctors, and these patients must not receive Xolair if they have ever had an allergic reaction to it. In clinical studies, variety of cancer types including breast, skin, prostate, and parotid were reported in more patients who received Xolair as compared to other patients who had not (Smith et al., 2008). b. Xolair should not be taken as a substitution for the asthmatic medicines that patients are taking already.  Further, asthmatic patients should not make alteration to their other asthmatic medications unless their doctor tells them (Miller et al., 2008; D’Amato et al., 2004) . c. Few patients on Xolair can have an irregular surge in eosinophils in their blood or tissues, which occasionally causes an irritation of vessels leading to rash, deteriorating of respirational indicators, heartbeat irregularities, and sometimes headache and physical-weakness (“Xolair (omalizumab)”, 2003; D’Amato et al., 2004; Heil, 2010). d. Some patients with subsequent doses of Xolair might experience joint inflammation and inflamed lymphomas (“Scientific Discussion- Xolair”, 2011). 10. Pharmacokinetic Features of Xolair: Following pharmacokinetic features have been identified for adults as well as adolescent patients: 10.1. Absorption: Xolair (all formulations) is found to be absorbed with a normal unconditional bioavailability of 0.62. More specifically, after a single subcutaneous dose in adult or adolescent asthmatic patients, omalizumab is found to be absorbing slowly, and reaches peak serum absorptions in a week or so (Smith et al., 2008; Rosenwasser, 2003). 10.2. Elimination: Elimination or clearance of active omalizumab is followed by IgG clearance along with its binding procedure that takes place with IgE. 10.3. Distribution: Omalizumab in Xolair constitutes complexes of limited volumes with IgE in vitro. More specifically stating, the evident volume of distribution of Xolair within asthmatic patients after subcutaneous dosages is found to be varying between 110 and 50 millilitres per kilogram (Busse et al, 2001). 11. Summary: Xolair (trade name of omalizumab) is a humanized IgG1 monoclonal antibody that specifically interacts with human immunoglobulin E (IgE), with melting points varying between 61 and 71°C, belonging to the category of immunomodulatory or anti-asthmatic agents (Smith et al., 2008). Xolair is produced by three stage process, involving a continued provision of mammalian cells under specific pressurized environment through the seed train, expansion of cell population through the provision of inoculum train, in order to introduce it into the production culture, and finally, development of commercial drug after careful storage and sterilization procedures (“Scientific Discussion- Xolair”, n.d.). In its commercial format, it is a sterilized grey/white lyophilized powder enclosed within a disposable vial which is rebuilt with sterile water, and is provided as a subcutaneous inoculation. Its action mechanism is identified as the activity of binding the IgE to the highly attractive Fc&RI, over the exterior of mast cells and basophils (Busse et al., 2001). Through this, it causes decline in surface bound IgE on Fc&RI bearing cells, which in turn limits the degree of release of mediators of the asthmatic allergic responses to relieve the condition of patient. As a primary drug used for the allergic asthma, subsequent clinical trials of Xolair suggest that it is equally effective and significant reliever in disorders like persistent allergic asthma, seasonal allergic rhinitis, perennial allergic rhinitis, type-I hypersensitivity, chronic urticarial, and atopic dermatitis, for both adults and children around 12 years of age (Chervinsky et al., 2003; Corren et al., 2004; Cowen, 2009). However, its efficacy is found to be varying (in comparison to that of adults) in the case of adolescents and pregnant women. On the other hand, the drug has some serious side effects associated with it, which comes usually under the umbrella of respiratory organ malfunctioning, skin itching, blood flow variations, throat stiffing, and nasal flows. Also, it is said to be the direct motivator of anaphylaxis, which is a serious allergic disorder that leads to abnormal reactions and excessive pain in abdomen, chest, nerves, or fever, skin irritation, coughing, and ultimately to patient’s death in some cases. Therefore, the subjects of Xolair are always advised to take precautionary recommendations in their mind, as the usage of Xolair is not based on short-durations, and this specific drug is a long-term reliever of the asthmatic allergies. Finally, Xolair’s pharmacokinetic features suggest that it’s absorption rate is slower (which is due to the intrinsic feature of slower absorption associated with omalizumab), it is cleared with the clearance of IgG through latter’s bond with IgE, and distributes slowly – in both adult and adolescent patients of asthmatic allergy (Smith et al., 2008; “Xolair (omalizumab)”, 2003). List of References Busse, W., Corren, J. & Lanier, B.Q. (2001): Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma, Journal of Allergy & Clinical Immunology, Vol. 108(2). Retrieved From: Accessed on: 6th May, 2011. Chervinsky, P., Casale, T. & Townley, R. (2003): Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis, Annals of Allergy, Asthma & Immunology, Vol. 91(2). Retrieved From: Accessed on: 5th May, 2011. Corren, J., Diaz-Sanchez, D. & Saxon, A. (2004): Effects of Omalizumab, a humanized monoclonal anti-IgE antibody, on nasal reactivity to allergen and local IgE synthesis, Annals of Allergy, Asthma Immunology, Vol. 93(3). Retrieved From: Accessed on: 8th May, 2011. Cowen, M. (2009): Benefits of Omalizumab Confirmed in Patients with Persistent Severe Allergic Asthma, MediaWire News. Retrieved From: Accessed on: 4th May, 2011. D'Amato, G., Liccardi, G., Noschese, P., Salzillo, A., D'Amato, M. & Cazzola, M. (2004): Anti-IgE monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases, Current Drug Targets & Inflammatory Allergy, Vol. 3 (3). Retrieved From: Accessed on: 8th May, 2011. Heil, P.H., Maurer, D., Klein, B., Hultsch, T. & Stingl, G. (2010): Omalizumab Therapy in Atopic Dermatitis: Depletion of LgE does not improve the clinical course – A Randomized, Placebo-Controlled and Double Blind Pilot Study, Journal der Deutschen Dermatologischen Gesellschaft, Vol. 8 (12). Retrieved From: Access on: 8th May, 2011. Miller, C.W.T., Krishnaswamy, N., Johonston, C. & Krishnaswamy, G. (2008): Severe Asthma and the Omalizumab Option, Clinical and Molecular Allergy, Vol. 6 (4) Retrieved From: Accessed on 8th May, 2011. Omalizumab, Drug Bank’s 2011 Online Archives. Retrieved From: Accessed on: 3rd May, 2011. Rosenwasser, L.J. & Nash, D.B. (2003): Incorporating Omalizumab into Asthma Treatment Guidelines: Consensus Panel Recommendations, Continuing Education Credit, Vol. 28 (6). Retrieved From: Accessed on: 4th May, 2011. Scientific Discussions – Xolair, European Medicines Agency, n.d. Retrieved From: Accessed: 4th May, 2011. Tanox, Inc. – 2010 Company Profile, Reference for Business. Retrieved From: Accessed: 6th May, 2011. Xolair (omalizumab), United Healthcare (Oxford) 2011 Archives. Retrieved From: Accessed: 7th May, 2011. Xolair (omalizumab), Pulmonary-Allergic Drugs Advisory Committee Meeting’s 2003 Archives. Retrieved From: Accessed on: 5th May, 2011. Xolair Fact Sheet (Xolair for Subcutaneous Use), Genentech 2011 Archives. Retrieved From: Accessed on: 5th May, 2011. Xolair – Historical Sales Facts (USA & Global), Genentech, 2011 Archives, Retrieved From: Accessed on: 8th May, 2011. Read More