NDC 66621-0150 Anascorp

Centruroides (scorpion) Immune F(ab)2 (equine)

NDC Product Code 66621-0150

NDC 66621-0150-2

Package Description: 1 VIAL in 1 CARTON > 10 mL in 1 VIAL (66621-0150-1)

NDC Product Information

Anascorp with NDC 66621-0150 is a a plasma derivative product labeled by Rare Disease Therapeutics, Inc. The generic name of Anascorp is centruroides (scorpion) immune f(ab)2 (equine). The product's dosage form is injection, powder, lyophilized, for solution and is administered via intravenous form.

Labeler Name: Rare Disease Therapeutics, Inc

Dosage Form: Injection, Powder, Lyophilized, For Solution - A dosage form intended for the solution prepared by lyophilization ("freeze drying"), a process which involves the removal of water from products in the frozen state at extremely low pressures; this is intended for subsequent addition of liquid to create a solution that conforms in all respects to the requirements for Injections.

Product Type: Plasma Derivative What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Anascorp Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CENTRUROIDES FAB2 ANTIVENIN (EQUINE) 3.8 mg/mL

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.
  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Antivenin - [EPC] (Established Pharmacologic Class)
  • Passively Acquired Immunity - [PE] (Physiologic Effect)
  • Venom Neutralization - [MoA] (Mechanism of Action)
  • Antivenins - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Rare Disease Therapeutics, Inc
Labeler Code: 66621
FDA Application Number: BLA125335 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 08-03-2011 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Anascorp Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

5.1 Hypersensitivity Reactions

Severe hypersensitivity reactions, including anaphylaxis, may occur with Anascorp. Close patient monitoring for hypersensitivity
reactions and readiness with intravenous therapy using epinephrine, corticosteroids, and diphenhydramine hydrochloride is
recommended during the infusion of Anascorp. If an anaphylactic reaction occurs during the infusion, terminate administration at
once and administer appropriate emergency medical care.
Patients with known allergies to horse protein are particularly at risk for an anaphylactic reaction. Patients who have had previous
therapy with Anascorp or another equine antivenom/antitoxin may have become sensitized to equine protein and be at risk for a severe
hypersensitivity reaction.

5.2 Delayed Allergic Reactions (Serum Sickness)

Monitor patients with follow-up visit(s) for signs and symptoms of delayed allergic reactions or serum sickness (e.g., rash, fever,
myalgia, arthralgia), and treat appropriately if necessary. Eight out of 1,534 (0.5%) patients in the clinical trials exhibited symptoms suggestive of serum
sickness. (6.1)

5.3 Transmissible Infectious Agents

Anascorp is made from equine (horse) plasma, it may therefore carry a risk of transmitting infectious agents, e.g., viruses.

5.4 Reaction To Cresol

Trace amounts of cresol from the manufacturing process are contained in Anascorp. Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug
cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
A total of 1534 patients were treated with Anascorp, ranging from less than one month to 90 years old. The patient population was
comprised of 802 males and 732 females. Patients were monitored for signs and symptoms of adverse reactions, including acute
hypersensitivity reactions and serum sickness. Follow-up telephone interviews were conducted at 24 hours, 7 days, and 14
days after treatment to assess symptoms suggestive of ongoing venom effect, serum sickness, and any other adverse reactions.
Table 1 shows the adverse reactions occurring in patients across all clinical trials for Anascorp. Twenty-seven percent (421/1534) of
patients receiving Anascorp reported at least one adverse reaction.
Table 1: Adverse Reactions Reported in ≥ 1% of PatientsADVERSE REACTIONSAnascorp [N=1534] n(%)Vomiting72 (4.7)Pyrexia63 (4.1)Rash41 (2.7)Nausea32 (2.1)Pruritus31 (2.0)Headache29 (1.9)Rhinorrhea28 (1.8)Myalgia25 (1.6)Fatigue24 (1.6)Cough22 (1.4)Diarrhea20 (1.3)Lethargy17 (1.1) No patients died or discontinued study participation for severe adverse reactions.
Eight patients were considered to have serum sickness (Type III hypersensitivity); no patient manifested the full serum sickness syndrome. Three
patients were treated with systemic corticosteroids and five others received either no treatment or symptomatic therapy.
34 patients experienced a total of 39 severe adverse reactions such as respiratory distress, aspiration, hypoxia, ataxia, pneumonia, and
eye swelling. It is not clear whether these adverse reactions were related to Anascorp envenomation or a combination of both.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Anascorp.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their
frequency or establish a causal relationship to drug exposure.

Chest tightness, palpitations, rash and pruritus.

8.1 Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Anascorp. It is also not known
whether Anascorp can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Anascorp should be given to a pregnant woman
only if clearly needed.

8.3 Nursing Mothers

It is not known whether Anascorp is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when
Anascorp is administered to a nursing woman.

8.4 Pediatric Use

Seventy-eight percent of the patients enrolled in the clinical studies were pediatrics subjects(1204/1534), with ages ranging from less than one
month to 18.7 years of age. Patient age groups were as follows: < 2 years of age, 29%, 2 to 5 years, 37%, 5 to 18 years, 34%. The
efficacy and safety of Anascorp is comparable in pediatric and adult patients.

8.5 Geriatric Use

Specific studies in elderly patients have not been conducted, Anascorp was administered to 77 patients over the age of 65 years
with comparable efficacy and safety to the overall patient population.

11 Description

Anascorp [Centruroides (Scorpion) Immune F(ab')2 (Equine) Injection] is a sterile nonpyrogenic, lyophilized, polyvalent preparation of equine immune globulin F(ab')2 fragments,
manufactured from plasma of horses immunized with with venom of
C. noxius, C.l. limpidus, C.l. tecomanus, and
C.s.suffusus. The product is obtained by pepsin digestion of horse plasma to remove the Fc portion of immune globulin, followed by fractionation and purification steps.
The F(ab')2 content is not less than 85%, F(ab) content is not more than 7%, and the product contains less than 5% intact immunoglobulin.
Each vial of Anascorp contains 45-80 milligrams of sodium chloride, 4.3 - 38.3 milligrams of sucrose, and 6.6-94.9 milligrams of glycine as stabilizers. Trace amounts of pepsin, cresol (< 0.41 mg/vial), borates (< 1 mg/vial) and Sulfates (< 1.7 mg/vial) may be present from the manufacturing process.
Each vial contains no more than 120 milligrams of protein and will neutralize at least 150 LD50 of Centruroides scorpion venom in a mouse neutralization assay.
The manufacturing procedures that contribute to the reduction of risk of viral transmission include pepsin digestion, ammonium sulfate precipitation/heat treatment
and nanofiltration.

12.1 Mechanism Of Action

Anascorp is composed of venom-specific F(ab')2 fragments of immunoglobulin G (IgG) that bind and neutralize venom toxins, facilitating
redistribution away from target tissues and elimination from the body.1

12.3 Pharmacokinetics

Eight clinically healthy volunteers (6 males and 2 females, age: 17 to 26 years) received a bolus intravenous dose of 47.5
mg of Centruroides (Scorpion) Immune F(ab’)2, (Equine) Injection. Blood samples were collected till 504 hours (21 days)
and pharmacokinetic parameters were estimated by non-compartmental analysis which are summarized in Table 2.
Table 2. Pharmacokinetic parameters of scorpion antivenomParametersMean ± sdAUC(0-∞)(µg•hr/mL)706 ± 352Clearance (mL/hr)83.5 ± 38.4Half-life (hrs)159 ± 57Vss (liters)13.6 ± 5.4

14 Clinical Studies

The efficacy of Anascorp was assessed in a prospective double-blind randomized placebo-controlled study, four open-label studies and one retrospective
study in various treatment settings in the United States and Mexico, where scorpion envenomation is common. A total of 1534 patients
ranging from less than one month to 90 years old were treated. The majority of patients (78%, 1204/1534) were pediatric, ranging
from less than one month to 18.7 years of age. Male (52.3%) and female patients (47.7%) were equally represented. Treatment
success was determined by resolution of clinically important signs of scorpion envenomation within four hours of starting infusion.
The randomized placebo study enrolled 15 subjects, eight to the Anascorp treated group and seven to the placebo. The symptom
resolution success rate was 100% for the Anascorp treated and 14.3% for the placebo group.
A retrospective hospital chart review provided historical data from envenomated patients (N=97) who did not receive antivenom but were treated with sedatives and supportive
care for symptoms of envenomation. These data were used as a historical control for expected outcomes in the absence of antivenom treatment. The historical controls were
pediatric patients admitted to two pediatric intensive care units between 1990 and 2003 for the treatment of scorpion envenomation
with supportive care only. The proportion of patients that required intensive care
support four hours after intensive care unit admission, and the overall duration of the intensive care support requirement were calculated.
Overall, 95-100% of patients were relieved of systemic signs associated with scorpion envenomation in less than four hours after
initiating Anascorp treatment. In the historical control database, only 3.1% of patients experienced relief of symptoms within 4 hours of hospital
admission.
In 1396/1534 patients the mean time from start of Anascorp infusion to resolution of clinical signs and symptoms of envenomation
was 1.42 hours (0.2 to 20.5 hours). Pediatric patients generally experienced a slightly faster time to resolution (1.28 ± 0.8 hours)
compared with that of adult patients (1.91 ±1.4 hours). The time to resolution of symptoms was not affected by use of sedatives
(474 patients who received sedatives resolved in 1.49 ± 1.1 hours and 922 patients who did not receive sedatives resolved in 1.38 ±
0.9 hours).

15 References

1. Krifi M.H, Savin S, Debray M, Bon C, Ayeb M.E, Choumet V. Pharmacokinetic studies of scorpion venom before and after antivenom immunotherapy.
Toxicon, 2005; 45: 187–198.2. Curry SC, Vance MV, Ryan PJ, Kunkel DB, Northey WT. Envenomation by the scorpion Centruroides sculpturatus, J Toxicol
Clin Toxicol , 1983-1984; 21(4-5): 417-49.3. Gibly R, Williams M, Walter FG, McNally J, Conroy C, Berg RA. Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion
envenomation. Ann Emerg Med,1999;34(5):620-5.4. Vasquez H, Chavez-Haro A, Garcia-Ubbelohde W, et al., Pharmacokinetics of a F(ab’)2 scorpion antivenin in healthy human volunteers, Toxicon,
2005;46: 797-805.5. Boyer LV, Theodorou AA, Berg RA, Mallie J. Antivenom for Critically Ill Children with Neurotoxicity from Scorpion Stings.
N Engl J Med,2009;360:2090-8.

16 How Supplied/Storage And Handling

  • Anascorp is supplied as a sterile lyophilized preparation in a single-use vial. When reconstituted, each vial contains not more than 24 milligrams per milliliter of protein, and not less than 150 mouse LD50 neutralizing units.Each carton NDC 66621-0150-2 contains 1 vial of Anascorp NDC 66621-0150-1.Store at room temperature (up to 25 ºC (77 ºF)). Brief temperature excursions are permitted up to 40 ºC (104ºF).DO NOT FREEZE.Discard partially used vials.

17 Patient Counseling Information

Advise patients to contact the physician or emergency department immediately if they experience any signs and symptoms of delayed
allergic reactions or serum sickness up to 14 days following hospital discharge. Symptoms include rash, pruritus, joint pain,
arthralgia, fever, lymphoadenopathy, and malaise.
Manufactured by:Instituto Bioclon S.A. de C.V.Mexico D.F., Mexicowww.bioclon.com.mxManufactured for:Rare Disease Therapeutics2550 Meridian Blvd., Suite 150Franklin, TN 37067www.raretx.comU.S. License No. 1860RDT Part No. Anascorp PI003PACKAGE LABEL

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