Somatropin (rDNA origin) - Omnitrope; human growth hormone, recombinant
Status - follow-on protein NDA approved in U.S.; biosimilar filing approved in EU
Organizations involved:
Sandoz AG –Manuf.; R&D; Tech.; Intl. Mark.
Novartis Pharmaceutical Corp. – USA mark.
Novartis AG – Parent
Cross ref.: See the Somatotropin (hGH) Products entry, and other somatropin product entries, particularly the entry for Genotropin (above) from Pfizer, of which this is a generic version.
Description: Somatropin or Omnitrope from Sandoz/ Novartis is a lyophilized (freeze-dried) formulation of recombinant human growth hormone (rhGH) manufactured by Sandoz AG, now the generics subsidiary of Novartis AG. It is commonly referred to as a generic version or copy of Genotropin from Pfizer; and is similarly produced using transformed Escherichia coli (E. coli). Omnitrope is substantially similar to other rhGH products, containing substantially the same hGH (somatropin), e.g., with 191-amino acids, and may become the first generic (based on approval mechanisms) biopharmaceutical approved in major markets (U.S. and/or European Union).
Omnitrope is packaged in vials containing 1.3 mg/mL powder; and as cartridges, 5 and 10 mL, containing 10 mg/1.5 mL for use in the Omnitrope Pen 10 reusable pen injector. The aqueous formulations of 5 mg/1.5 mL Omnitrope cartridge and 10 mg/mL Omnitrope® cartridge are bioequivalent to the lyophilized 5.8 mg/vial Omnitrope formulation. After powder reconstitution, 1 mL contains 1.3 mg Somatropin (corresponding to 4 IU). Excipients in the cartridges are glycine, disodium hydrogen phosphate, sodium dihydrogen phosphate dihydrate, Poloxamer 188, mannitol, phenol, Water for Injection and benzyl alcohol. Diluent vials contain benyzl alcohol (17 mg) and Water for Injection to make 1.14 mL. The product is stored at 2-8˚C (refrigerated).
Nomenclature: Somatropin, rDNA/Sandoz [BIO]; somatropin [FDA INN]; Omnitrope [TR]; somatropin (human) [CAS]; 12629-01-5 [CAS RN]; human growth hormone, recombinant [SY]; NDC 43858-700-01 and NDC 43858-701-01 [NDC]
Companies.: Omnitrope was developed and the bulk substance is manufactured by Sandoz AG, Vienna, Austria, with filling and finishing at Novartis AG, Stein, Switzerland. Sandoz is now the name adopted by Novartis AG for its generics subsidiary. Sandoz originally was an international pharmaceutical company which merged with Ciba-Geigy to form Novartis (i.e., the Sandoz corporate name has been revived).
Manufacture: The active substance bulk solution is manufactured, tested and released by Sandoz GmbH, Kundl, Austria. Active substance manufactured by Covance Biotechnology Services Inc., now Diosynth RTP, was also used during development, However, the Kundl process and product is used for commercial supplies
During development several process changes were introduced, including a transfer of production to Covance, and a later a re-transfer to Sandoz GmbH. Several improvements to the purification process were implemented at these manufacturing sites, leading to a modified downstream manufacturing process with significantly enhanced host cell protein (HCP) clearance.
FDA class: Drug NDA
Approvals: Date = 20060530; original NDA
Date = 20080128; ; NDA supplement; Indication = new strength cartridge (5 mg) of the liquid formulation for use in a new reusable injector pen, Omnitrope Pen 5
Date = 20080825; NDA supplement; Indication = new strength cartridge (10 mg/1.5 mL) of the liquid formulation for use in a new reusable injector pen, Omnitrope Pen 10
Date = 20100628; NDA supplement; Indication = treatment of children with growth failure due to Prader-Willi syndrome and for those who are small for gestational age
Date = 2010826; NDA supplement; Indication = “Prior Approval” supplemental new drug application provides for the addition of the following new indication: to treat pediatric patients with idiopathic short stature (ISS)
Date = 20110411; NDA supplement; Indication = a “Changes Being Effected” supplement adding text to the Warning and Precautions section of the package insert regarding risks of pancreatitis
Indications: [full text of the "Indications and USAGE" section of product insert/labeling; 6/2012]:
Status: A roughly chronological discussion of FDA and EU actions (or inaction) and approvals follows.
Sandoz Inc. (and Biochemie U.S. Inc., also a Novartis subsidiary) filed an NDA with FDA in July 2003, and Sandoz/Novartis AG filed in the European Union (EU) in June 2003 seeking approval of Omintrope as what some may considered the first generic (biosimilar, biocomparable, biogeneric, follow-on) recombinant biopharmaceutical. Omnitrope was compared to Genotropin from Pfizer, the world market leader among hGH products (see related entry above). Sandoz did not file for approval of Omnitrope as a true generic drug, i.e., did not request officially allowing pharmacy substitution of Omnitrope for Genotropin (or other somatropin products). Rather, it sought approval with the abbreviated testing requirements allowed by FDA under section 505(b)(2) of drug regulations and under new EU biosimilar approval guidelines.
Sandoz submitted its NDA for Omnitrope in July 2003 as a 505(b)(2) NDA rather than 505(j), because sponsors can submit clinical data with a 505(b)(2) application. Most generic drugs are approved under 505(j) ANDA’s, and only some (several hundred) have been approved under 505(b)(2). 505 (j) ANDAs (paper NDAs) include only bioavailability studies and preclinical data showing comparability to an innovator product and incorporate by reference the innovator’s clinical trial data. However, Sandoz’s NDA included chemistry, nonclinical pharmacology and toxicology, immunogenicity data requested by FDA, and clinical trials, including bioequivalence studies with Genotropin. Sandoz reported FDA had “not needed and have not referenced or used any non-public data” to review the Omnitrope application, “and especially has not needed to rely on any data in the Genotropin section.”
Ominitrope’s NDA application sought approval under section 505(b)(2) of the Food, Drug and Cosmetic Act, which allows approval of drugs (not biologics or medical devices) based on abbreviated clinical trials (e.g., shortened/smaller or no Phase III trials) by demonstrating comparability, including bioequivalence (pharmacokinetics), to an already-approved drug(s). Several hundred generic drugs in the U.S. have been approved under 505(b)(2). The target date for FDA action on the NDA was originally in August 2004. The NDA was very controversial, including multiple lawsuits against FDA filed by current U.S. hGH marketers, and FDA stalling action on the NDA while it tried to develop broad guidelines (yet to be issued) concerning follow-on protein 505(b)(2) drug approvals.
During the NDA pendency, FDA Commissioner Dr. M. McClellan had explicitly stated that the agency has the authority to use 505(b)(2) to approve rhGH products based on less clinical data than would be required for a full NDA. The FDA defended this position in its response to citizen petitions filed by the Biotechnology Industry Organization (BIO) and several companies. FDA plans to eventually release a draft guidance document outlining the basis for approval of rhGH products (which will set precedents for other such recombinant proteins regulated as drugs).
Sandoz/Novartis applied for 505(b)(2) generic drug approval with New Chemical Entity (NCE) designation, which provides five years of marketing exclusivity. However, as shown by recent biogeneric-like approvals of hyaluronidase and other products (e.g., glucagon and calcitonin), FDA has granted approvals with NCE to each follow-on product (considering each product unique, despite approval based on an abbreviated NDA), with this market exclusivity not likely to prevent other newer somatropins (given NCE status) from being approved. Thus, NCE status may not bring any advantages, other than to allow FDA to avoid the very difficult issue of designating generic equivalence, i.e., allowing substitution of products when filling prescriptions. NCE status meand that Omnitrope is not officially substitutable for Genotropin, since it is recognized as being unique.
On Aug. 31, 2004, FDA sent Sandoz a letter stating that it was “unable at this time to reach a decision on the approvability of the [Omnitrope] application because of unresolved scientific and legal issues that relate to [the] NDA.” Sandoz noted FDA did not cite any scientific or regulatory deficiency in the NDA and did not request any additional information. [Further information about later FDA actions follows below].
On Oct. 4, 2004, the Australian Therapeutic Goods Administration approved Omnitrope – the first approval of the product anywhere. This approval is officially not a biosimilar- or generic-type approval. Approval was supported by preclinical data and a single small Phase III trial that compared Omnitrope to Genotropin from Pfizer. Sandoz claimed its studies demonstrated pharmacokinetic, pharmacodynamic and safety features similar to Genotropin, including bioequivalence in a Phase I trial with an undisclosed number of subjects. The Phase III trial was conducted in Warsaw, Poland, in children with proven insufficient secretion of pituitary growth hormone received Omnitrope (n = 44) or Genotropin (n = 45), with similar results for both products. Omnitrope recipients were followed for 21 months and, according to Sandoz, experienced “clinical effects similar to those reported for currently marketed hGH products.” The Australian product insert/label describes a 24-month trial in 169 children treated with two doses compared to 40 untreated controls. Unlike all U.S. and EU approval to date for somatropin products, which involved trials for each approved indication, the Australian label includes children Turner’s syndrome and chronic renal insufficiency that Sandoz had not studied in trials. Despite Australian drug authorities emphasizing that this was not a biosimilar/generic approval, Sandoz’s press release reported this as “the first product to be developed as a biosimilar and to be approved for clinical use in Australia,” and similarly referred to it as a “biosimilar” in a letter to Austrian physicians and in marketing pieces. Austrian authorities have accepted the European Community guidelines for biosimilars, but have not used these as the basis for any product approvals.
Sandoz and the European Medical Evaluation Agency (EMEA) were involved in a complex dispute over Omnitrope, much of which has not been reported publicly. The EU application received a positive recommendation from the Committee for Proprietary Medicinal Products (CPMP), EMEA, EU, on June 26, 2003. In its limited public disclosure, EMEA stated, “The benefits of Omnitrope have been demonstrated by efficacy results obtained with the liquid formulation, supportive clinical studies performed with a lyophilized formulation, and the results mentioned in the literature for other, well-known, growth hormone containing products. It is concluded that the efficacy of Omnitrope parallels that of other growth hormone containing products.” EMEA also recognized that the comparability testing program for Omnitrope ““has taken into account the nature of the molecule, the knowledge of the mode of action of the molecule and the experience with growth hormone in clinical use.” The application included abbreviated clinical trials data for which prior consultations with EMEA, starting in 2000, had indicated would be sufficient to support EU approval.
However, the European Commission (EC) subsequently refused to approve the application, with EMEA and/or the Commission apparently unexpectedly having changed approval criteria for Omnitrope, and/or delaying the application due to controversial aspects. Sandoz received a formal letter regarding this rejection on Nov. 13, 2003, with the application sent back to CPMP for reconsideration. An EU spokesman cited “certain procedural issues” as the cause of rejection. Sandoz/Novartis filed a lawsuit on Jan. 14, 2004, in the European Court of First Instance asserting that the EC improperly refused to issue an approval and requesting that the court force the EC to approve Omnitrope.
This was the first time ever that EC had not followed CPMP/EMEA recommendations for product approval. Sandoz/Novartis has not disclosed the details of the contents of its application, but the EU application presumably paralleled that of its Australian application (discussed above). Although Sandoz reports that it followed all EMEA guidelines, suggestions and procedures, the novelty of the first approval of a product under EU biosimilar regulations likely caused the delays in its EU approval. EMEA published a guidance document for biosimilar approvals in early 2004. The rejection/delay in the EU was somewhat unexpected and ironic, since most European governments, themselves, provide health care and pharmaceuticals to their populations, unlike the U.S. with its variety of private and public sector insurers, and these countries have been very eager to decrease their pharmaceutical costs through generic competition. [See discussion about EU approval below].
In April 2004, Genentech Inc., manufacturer and marketer of the Nutropin brand of somatropin, filed a citizen’s petition with FDA objecting to the agency’s plans to implement 505(b)(2) generic (follow-on protein) drug approvals for certain recombinant proteins, based on the premise that FDA review of any generic application would, by necessity, involve comparison with the innovator/pioneer product’s applications, which would involve violation of confidentiality and illegal usage and taking of the original applicant’s proprietary product and process information. The petition contends that FDA cannot legally use proprietary data from another company’s NDA (or BLA) to approve a biogeneric/follow-on protein, and that it is impossible to review a biogeneric without using this data, e.g., that it is impossible to approval Omnitrope without using Genentech’s or other current U.S. marketer’s application. Genentech alleged that pioneer/innovator product companies need to be formally included in FDA’s deliberations, and that the process needs to be more open/public, including given companies formal notice of the use of proprietary data and the right to seek legal remedies (which would substantially delay or block a biogeneric filing).
In May 2004, Pfizer Corp., manufacturer and marketer of Genotropin brand of somatropin, filed a citizen’s petition with FDA requesting immediate denial of the NDA for Omnitrope. Objections included allegations that FDA could not possibly fully evaluate and approval Omnitrope without using Genotropin data proprietary to the company. Pfizer also filed protests with European Union authorities concerning their consideration of Omnitrope and use of its proprietary information.
In late June 2004, Sandoz responded to Pfizer and other vocal critics that recombinant glucagon from Novo Nordisk A/S, marketed as GlucaGen (entry #166) had already set a precedent for approval of a recombinant product based on limited bioequivalence studies. GlucaGen was approved in June 1998 based primarily on studies showing bioequivalence to animal-derived glucagon and a small safety study in healthy volunteers, along with references to the scientific and medical literature. Sandoz/Novartis’ response included accusing Pfizer of having “unclean hands,” because it submitted into the public record (FDA public docket) a copy of a confidential Sandoz draft protocol for a trial comparing Omnitrope and Pfizer’s Genotropin. Sandoz/Novartis also noted that Pfizer’s allegations that Genotropin and Omnitrope are two distinct products was based on a typographical error in this draft document misstating the molecular weight of Omnitrope hGH with a 1,001 daltons (1 kDa) difference between the products, such that Omnitrope hGH would have to be composed of only 184 amino acids, rather that hGH’s 191.
In Sept. 2004, Sandoz received notice from FDA that the it was unable to reach a decision on whether to approve Omnitrope. This came after FDA had extended the PDUFA date (target decision date) by 90 days. FDA had completed its review of Omnitrope, and did not identify any deficiencies in the application. However, FDA was unable to render a decision “due to uncertainty regarding scientific and legal issues,” and probably political concerns, too, while its overdue follow-on protein regulations remained similarly unresolved or in limbo. This (in)action conflicted with FDA statements that it has the legal authority under 505(b)(2) of the Food, Drug and Cosmetic Act to approve abbreviated applications for biopharmaceuticals regulated as drugs, such as somatropin or insulin, that are substantially similar to marketed drugs. FDA delayed its originally planned release of draft guidelines for follow-on protein approvals until summer 2005 (still yet to be released), and FDA signalled that is would prefer to wait to act on Omnitrope and follow-on protein guidelines to allow Congress to resolve related issues.
On Jan. 17, 2006, Sandoz filed suit (Sandoz Inc. v. Michael Leavitt, Secretary of Health and Human Services, case no. 05-1810) in U.S. District Court (Washington, DC) seeking a summary judgment to force FDA to render a decision concerning the NDA for Omnitrope. Sandoz contended that if the court does not compel the FDA to act, it would give the agency “effectively unlimited discretion” in how it handles drug applications, and “The agency’s unusual silence in managing the Omnitrope NDA review is without any statutory foundation and if let unredressed threatens to undermine all notions of administrative regularity.” The suit sought to force FDA to either approve or disapprove Omnitrope within 10 days of the judgment, to rule that Section 505(b)(2) can be used as a regulatory pathway for biologic drugs, and to force the FDA to approve Omnitrope unless the agency can cite a valid reason for not approving the drug. FDA is required to act on an NDA within 180 days, but often ignores such timelines when politically sensitive issues are involved.
On April 13, 2006, the U.S. District Court judge ruled in favor of Sandoz/Novartis’ suit seeking to force FDA to render a decision regarding the Omnitrope NDA. The judge ruled that Novartis is “entitled to an end to this marathon round of keep-away and soon;” that FDA “asks the court to excuse its delay, accept governmental mediocrity and vitiate the statute’s mandatory language,” [regarding requirements for 180 turnaround on NDAs]; and that FDA “has identified no compelling reason for this court to excuse its delay.” The judge did not rule on FDA precedents and policies concerning follow-on protein drugs. With 505(b)(2) regulations well-established, FDA having the authority and already setting precedents for approval of recombinant therapeutics under this, and with Pfizer almost certainly having filed an application showing comparability to Genotropin, including in clinical trials, FDA had no basis to not approve the NDA.
On May 30, 2006, Sandoz/Novartis received FDA approval (NDA) for Genotropin under under Hatch-Waxman Act-derived section 505(b)(2), the same regulations that have been used for approval of hundreds of generic drugs. Although the approval was based on comparisons with Genotropin, FDA did not grant therapeutic equivalence, the ability to substitute Omnitrope for Genotropin and/or other marketed somatropins. Somewhat paradoxically (with approval based on comparisons), as it had with other recent 505(b)(2) generic drug approvals of biopharmaceuticals, FDA granted Omnitrope New Chemical Entity (NCE; New Molecular Entity), designating it as new and unique, with this including six months of market exclusivity concerning approvals during this period. This exclusivity, as with other recent similar approvals, is rather meaningless, since each such generic drug approval of biopharmaceuticals by FDA has granted this, so none of the products’ approvals would effectively bar subsequent approvals during the exclusivity period.
In Jan 2007, lyophilized powder form of Omnitrope was launched in the U.S. by Sandoz..
With its approval, FDA class:ified Omnitrope as “BX” (insufficient data to determine therapeutic equivalence) in its Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).
On April 18, 2005, Sandoz/Novartis received European Union MAA approval for Omnitrope. The European Medicines Agency’s Committee on Medicinal Products for Human Use (CHMP) had issued a positive opinion recommending approval of Omnitrope on Jan. 27, 2006. [Recall that in June 2003, the CPMP (Committee’s name at that time) recommended that the European Commission grant approval for Omnitrope, but the Commission refused]. Novartis is launching Omnitrope in the EU as quickly as it can negotiate prices country-by-country, starting with Germany and Austria. The reference medicinal product for this approval was Genotropin from Pfizer (formerly Pharmacia), originally authorized in the EU in 1988. The EU supported Pfizer’s claims that Omnitrope is similar (biosimilar) to Genotropin. As required for a Similar Biological Medicinal Product application, the dossier contained a full quality Module 3 and reduced non-clinical and clinical Modules 4 and 5, with the required elements of the comparability exercise/trials, respectively as required by the EU CHMP guidelines. The active ingredient of Omnitrope complies with the Ph. Eur. Monograph Somatropin Bulk Solution and is compared with the Ph. Eur. standard (somatropin CRS).
The EU approved indications: are “Growth disturbance due to insufficient secretion of growth hormone and growth disturbance associated with Turner syndrome or chronic renal insufficiency. Growth disturbance (current height SDS < -2.5 and parental adjusted SDS < -1) in short children born small for gestational age (SGA), with a birth weight and/or length below -2 SD, who failed to show catch-up growth (HV SDS < 0 during the last year) by 4 years of age or later. Prader-Willi syndrome (PWS), for improvement of growth and body composition. The diagnosis of PWS should be confirmed by appropriate genetic testing. Replacement therapy in adults with pronounced growth hormone deficiency.” An Omnitrope liquid pen system has been available in Europe since spring 2007.
In April 2007, in “The FDA’s assessment of follow-on protein products: a historical perspective,” Nature Reviews Drug Discovery, published online on April 13, 2007, FDA rationalized its prior biogeneric/follow-on protein-like approvals. Regarding Omnitrope, FDA noted, “ Omnitrope was the first recombinant human-growth hormone product approved by the FDA under an abbreviated approval pathway. The approval relied on, among other things, physicochemical, pharmacokinetic, pharmacodynamic and clinical data comparing Omnitrope with Genotropin, a recombinant growth-hormone product approved in 1985. The clinical comparative data were from two controlled trials (6-month and 3-month durations) in 86 paediatric subjects (89 subjects enrolled; 86 subjects completed the 6- and 3-month trials) that directly compared Omnitrope and Genotropin for the treatment of growth failure due to inadequate secretion of endogenous growth hormone (pediatric growth-hormone deficiency). In addition to these comparative data, the FDA reviewed certain non-clinical pharmacology data specific to Omnitrope: an additional controlled trial supporting the safety and effectiveness of a reformulated version of Omnitrope for injection (the marketed version) and liquid Omnitrope in pediatric growth hormone deficiency (involving the same 86 subjects as in the comparative studies), and safety data from a 24-month uncontrolled trial in 51 subjects that provided support for Omnitrope’s long-term safety and confirmation of an acceptable level of immunogenicity (for further details, see the FDA response to the Omnitrope citizen petition).The comparative data established that the active ingredients in Omnitrope and Genotropin have highly similar structures and Omnitrope and Genotropin have highly similar pharmacodynamic and pharmacokinetic parameters, as well as similar clinical performance (safety and effectiveness) in a growth-hormone-deficient pediatric population. The comparative data permitted the FDA to rely, in part, on its finding that Genotropin is safe and effective to support its conclusion that Omnitrope is safe and effective for the same indications:, including indications: (paediatric and adult) for which Omnitrope was not studied.”
On April 20, 2009, Health Canada approved Omnitrope, the first version of a previously approved recombinant biologic drug to be approved by Health Canada under Subsequent Entry Biologics (SEB; biosimilar) regulations.
Medical: The weekly dose should be divided over 6 or 7 days of subcutaneous injections.
Benzyl alcohol, a component of Omnitrope Cartridge 5 mg/1.5 mL and the diluent for Omnitrope® for injection 5.8 mg/vial, has been associated with serious adverse events and death, particularly in pediatric patients,.including “gasping syndrome."
Trials: See discussion above of trials used to support approval in Australia. Sandoz/Novartis conducted preclinical and clinical studies, including trials comparing Omnitrope with Genotropin from Pfizer Corp., with on trial considered a Phase III trial. Sandoz conducted more testing than wouqld be needed for generic approval of most small molecule drugs. This included a small Phase III trial compared Omnitrope and Genotropin treatment in children with growth hormone deficiency, but not for other hGH-approved indications:. Two open label efficacy trials were also included in the NDA –a trial comparing the two drugs and a trial in which Omnitrope was substituted for Genotropin. A 2-week cross-over pharmacokinetics/pharmacodynamics study was also conducted in 24 healthy patients.
Market: As with other generic (biosimilar, biocomparable, follow-on protein, etc.) biopharmaceuticals in development and/or marketed in internationally (where lack of patent protection allows), Omnitrope is marketed at a discount relative to existing products. Industry analysts had projected, at best, a discount of up to 30% relative to innovator brands. This discount is much less than the ~50% or more discount for most generic drugs (small molecules, usually manufactured inexpensively by synthetic means). Besides higher manufacturing costs compared to most generic drugs, in the U.S., EU and perhaps other countries, Sandoz/Novartis will likely be required to conduct expensive post-marketing studies.
Sandoz generally sells Omnitrope at a ~25% discount relative to other hGH products. Overall unit sales of hGH products have increased steadily since launch of Omnitrope, but market penetration has been minimal.
In the U.S., Omnitrope was launched in 2006 with about a 30% discount relative to leading somatropins. Discounts widened to ~40% in 2008, with leading competitors actually raising their prices (and probably providing discounts not reported through WAC or other mechanisms).
In 2009, Omnitrope worldwide sales were reported to be $127.6 million in 2011 and about $60 milion in 2009.
Total 2008 sales of Omnitrope were estimated by one published market study to be $30 million.
The 2007 Average Wholesale Price (AWP) is $1,708.00 for 8 5.8 mg vials.
In March 2008, upon its U.S. launch, the Omnitrope Pen 5 with liquid cartridge was being sold at $33.65/mg, which is about 35% less than the published price for Genotropin, the comparator reference product, and other leading recombinant growth hormones..
Omnitrope is being sold at an 25% discount in Australia, relative to Genotropin, suggesting a similar discount will be implemented upon launch in the U.S. and European Union. Sandoz submitted this 25% discounted price to the Schedule of Pharmaceutical Benefits for the Australian government’s reimbursement program.
Although the expected discounted price of Omnitrope will help it rapidly gather market share with minimal marketing, it will not be a major product for Pfizer, the largest pharmaceutical company in the world. There are too many competing products, further competition from other biogeneric versions can be expected, and it is used primarily for orphan indications:. However, Omnitrope will be profitable and will give Sandoz/Novartis visibility and a reputation as a pioneer in biogenerics. However, Omnitrope could probably have been approved in the U.S. and EU years ago and for comparable or less cost (considering Sandoz’ legal fees), if the company had simply conducted the usual Phase III trials and filed a full NDA (avoided its 505(b)(2) filing)..
In June 2010, Sandoz/Novartis announced changes to OmniSource, the support program for patients taking Omnitrope, replacing the Sandoz Access program with what it called a more extensive range of programs, higher-value reimbursement and expanded insurance features. Sandoz noted that patients could save up to $3,000 per year in out-of-pocket costs for Omnitrope prescriptions through the "Save As You Grow" program.
In June 2010, the National Institute for Health and Clinical Excellence (NICE), U.K., recommended approval of Omnitrope for treatment of child growth deficiencies. Somatropin is the only active treatment approved for children who are not growing normally, so the decision to fund use on the NHS will be welcome by those affected. At the time, the seven versions of somatropin approved for the NHS were: Pfizer's Genotropin; Eli Lilly's Humatrope; Novo Nordisk's Norditropin SimpleXx; Ipsen's NutropinAq; Merck Serono's Saizen; Ferring's Zomacton; and Omnitrope, the only follow-on biologic.
Companies involvement:
Full monograph
255 Somatropin, rDNA/Sandoz
1.1 Pediatric Patients
Omnitrope (somatropin [rDNA origin] injection) is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone (GH).
Omnitrope [somatropin (rDNA origin) injection] is indicated for the treatment of pediatric patients who have growth failure due to Prader-Willi Syndrome (PWS). The diagnosis of PWS should be confirmed by appropriate genetic testing [see Contraindications (4.2) and Warnings And Precautions].
Omnitrope [somatropin (rDNA origin) injection] is indicated for the treatment of growth failure in children born small for gestational age (SGA) who fail to manifest catch-up growth by age 2 years.
Omnitrope [somatropin (rDNA origin) injection] is indicated for the treatment of growth failure associated with Turner syndrome.
Omnitrope (somatropin [rDNA origin] injection) is indicated for the treatment of idiopathic short stature (ISS), also called non-growth hormone-deficient short stature, defined by height standard deviation score (SDS) ≤ -2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means.
1.2 Adult Patients
Omnitrope® (somatropin [rDNA origin] injection) is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:
Adult Onset (AO): Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
Childhood Onset (CO): Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.
Patients who were treated with somatropin for growth hormone deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for growth hormone deficient adults. Confirmation of the diagnosis of adult growth hormone deficiency in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.
Nomenclature:
Somatropin, rDNA/Sandoz [BIO]
somatropin [FDA INN]
somatropin (human) [CAS]
12629-01-5 [CAS RN]
hGH [SY]
human growth hormone, recombinant [SY]
rhGH [SY]
Omnitrop [TR Europe]
NDC 43858-700-01 and NDC 43858-701-01 [NDC]
molecular weight (kDa) = 22
FDA Class: Drug NDA biogeneric follow-on protein 505(b)(2)
Year of approval (FDA) = 2006
Date of 1st FDA approval = 20060530
(in format YYYYMMDD)
Biosimilars/biobetters-related U.S. Patents: | expired (Orange Book); approved as 505(b(2) generic drug, no biosimilars possible; 2004 arbitrarily used as expiration date |
U.S. Patent Expiration Year: | |
U.S. Biosimilars Data Exclusivity Expiration: | |
U.S. Biosimilars Orphan Exclusivity Expiration: | |
U.S. Biosimilars Launchability Year: | 2004 |
U.S. Biobetters Launchability Year: | 2004 |
Biosimilars/biobetters-related EU Patents: | approved as biosimilar, no biosimilar versions possible; 2004 arbitrarily used as expiration date |
EU Patent Expiration Year: | 2004 |
EU Biosimilars Data Exclusivity Expiration: | |
EU Biosimilars Orphan Exclusivity Expiration: | |
EU Biosimilars Launchability Year: | |
EU Biobetters Launchability Year: | 2004 |
Index Terms:
biopharmaceutical products
Biorex-70 resin
growth hormones
hormones
recombinant DNA
Escherichia coli (E. coli)
benzyl alcohol
disodium hydrogen phosphate
glycine
lyophilized (freeze-dried)
sodium dihydrogen phosphate
4D5 murine hybridoma cells
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
BHK-21 (C-13)
EU200 Currently Approved in EU EU777
UM001 Marketed Product in US
US200 Currently Approved in US US777
EM001 Marketed Product in EU
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