Calomist

Approval Date
July 27, 2007

Release Date
December 2007

Product
Calomist

Company
Fleming

Class
Hematinic

Indication
Maintenance of Vit. B₁₂ concentrations afternormalization with IM Vit. B₁₂ therapy in patients with Vit. B₁₂deficiency who have no nervous system involvement.

Active Ingredient
Cyanocobalamin 25micrograms/spray; nasal spray.

Agency Roster
S&R Communications Group (professional)

MarketingStrategy/Execution
Calomist is the firstand only FDA-approved, once-daily vitamin B12 nasal spray for patients withvitamin B12 deficiency. The marketing message for Calomist centers on ease ofuse and therapeutic effect; competitive products are multiple dosed or injectedand must be administered in a physician’s office. Fleming, which developed the product as an alternative to ongoingB12 injections, has a small, 30-person sales force and will market the drug topotential high-prescribing specialists, including gastroenterologists,nephrologists and endocrinologists. To extend its promotional reach, Flemingreached a deal with Hawthorn Pharmaceuticals, whose 135 reps will seek todetail some of the same specialists but mainly the larger physician base ininternal medicine. Fleming is committing to professional print media, as well.At this time, there are no plans for DTC advertising, said Max Draughn,president and CEO of Hawthorn.

The Market

Also in the Pipeline(according to Adis R&D Insight)
No competitor compounds in phase III or pre-registration, US

Recent MM&M Coverage

S&RCommunications Group

Pharmacology
Vitamin B₁₂ is essential for cell growth andreproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Rapidlydividing cells (e.g., epithelial cells, bone marrow, myeloid cells) have thegreatest requirement for Vit. B₁₂. It is also essential for theconversion of methylmalonate to succinate and for the synthesis of methioninefrom homocysteine. In the blood, Vit. B₁₂ is bound to transcobalaminII (a carrier protein) and is distributed to tissues and stored primarily inthe liver and bone marrow. A deficiency of Vit. B₁₂ in the bodyprevents tetrahydrofolate from being regenerated and results in functional folatedeficiency. Vit. B₁₂ may also play a role in sulfhydryl-activatedenzyme systems associated with fat and carbohydrate metabolism and proteinsynthesis.

Clinical Trials
A trial involving 25 Vit. B₁₂ deficient patientswas conducted to assess the efficacy and safety of Calomist. Prior toenrollment, all subjects were required to have normal Vit. B₁₂levels with intramuscular Vit. B₁₂₁₂ deficiency could not be confirmed. The 24remaining patients were stabilized on intramuscular Vit. B₁₂ therapyand given once daily (50mcg) intranasal dosing with Calomist for 8 weeks. Theserum Vit. B₁₂ concentrations were within the target range (>200ng/L)and slightly higher than those seen 2 to 4 weeks after administration ofintramuscular Vit. B₁₂; the mean serum Vit. B₁₂ level wasabout 570ng/L at week 8 of the trial. Twenty-three of the 24 patients received50mcg of Calomist daily for the duration of the trial and one patient requireddoubling of the Calomist dose from 50mcg to 100mcg daily during the last weekof the study because of declining Vit. B₁₂ concentrations. injections. One of the 25patients dosed with Calomist was excluded from the efficacy analyses because adiagnosis of Vit. B.

Adverse Reactions
Rhinorrhea, nasopharyngitis, arthralgia, dizziness, headache,nasal discomfort, pain, bronchitis, rash.

Adults
Not for newly diagnosed Vit. B₁₂ deficiency.Initially 1 spray in each nostril daily (50micrograms/day); if responseinadequate, may increase to twice daily dosing (100micrograms/day). Renal orhepatic impairment: may require increased dosing or frequency.

Children
Not recommended.

Precautions
Avoid in Leber’s disease. Vit. B₁₂ concentrationsshould be normal prior to treatment; switch to IM injections if levels are lowor decline. Nasal pathology; defer until nasal symptoms subside. Infections,uremia, concurrent iron, folic acid deficiency; may blunt therapeutic response.Obtain hematocrit, reticulocyte count, Vit. B₁₂, folate, and ironlevels prior to and during treatment. Monitor potassium and platelet countduring intense megaloblastic anemia treatment. Pregnancy (Cat.C). Nursingmothers.

Interactions
Iron supplements or bone marrow suppressants (e.g.,chloramphenicol) may blunt therapeutic response. Antibiotics, methotrexate,pyrimethamine may interfere with lab tests. Do not use for Schilling Test.