LAVIV
November 15, 2011 zhion@zhion.com    
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LAVIV is the first FDA approved cellular therapy to treat the wrinkles of the laugh lines of the smile lines. LAVIV is unlike
the facial fillers made of hyaluronic acid or calcium hydroxylapatite. The Miami Institute in Brickell is the first practice in
South Florida to start using this novel treatment. The cost for LAVIV treatment is between $3,000 and $3,500. (11-2011)

Proprietary Name: LAVIV®

Established (USAN) Name: azficel-T

Indication: LAVIV® is indicated for improvement of the appearance of moderate to severe nasolabial fold wrinkles in
adults.
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LAVIV Product description

The active ingredient in azficel-T is autologous cultured fibroblasts. The fibroblasts are cultured, using standard
methodologies, from three 3-mm punch biopsies (dermal and epidermal layers) taken from a patient’s post-auricular
area. Fibroblasts, due to their proliferative nature, expand more rapidly in culture than the other dermal cell types
present, such as keratinocytes. Fibroblasts represent more than 98% of the final product. Following in vitro expansion,
the fibroblasts are harvested and quality control tests are performed. The cell suspension is cryopreserved in protein-
free media containing DMSO at a defined cell concentration. When required for clinical use, a dose of cells is thawed,
washed, formulated to 1.0–2.0 x 107 cells/ml and shipped to the clinical site at 2-8°C by overnight delivery for use within
24 hours of final formulation. The cells are injected intradermally into the nasolabial folds in three separate doses given
four to six weeks apart.

No preclinical studies were conducted with azficel-T.

Approximately 1100 subjects received azficel-T at 110 clinics during the 4-year period when the product was marketed
in the US (see section 2 Background above). The applicant states that no serious adverse events were reported during
this time. Considering this previous commercial experience in humans, and due to the lack of an appropriate animal
model for wrinkles, no preclinical studies using azficel-T were necessary.

LAVIV Efficacy
The co-primary efficacy endpoints for the two pivotal trials were:

Proportion of subjects with at least a two-point improvement, from baseline to six months post-treatment, in wrinkles in
both nasolabial folds, using the Evaluator Wrinkle Severity Assessment, a blinded, live assessment using a 6-point
ordinal scale (Lemperle scale).

Proportion of subjects with at least a two-point improvement, from baseline to six months post-treatment, in the Subject
Wrinkle Assessment, a global 5-point self-assessment of the lower part of the face.
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LAVIV DOSAGE AND ADMININSTRATION
For autologous intradermal injection only Only healthcare providers who have completed a Fibrocell-approved training
program should administer LAVIV. Inject LAVIV at 0.1 milliliter per linear centimeter into the nasolabial fold wrinkles. The
recommended treatment regimen is three treatment sessions at 3-6 week intervals.
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LAVIV SAFETY ISSUES
The safety and efficacy of LAVIV for areas other than the nasolabial folds have not been established.
The efficacy of LAVIV beyond six months has not been established.

CONTRAINDICATIONS
Allogeneic use
If LAVIV is administered to a patient who is not the individual whose skin was used to produce the LAVIV, serious
immunological reactions can occur. Each vial of LAVIV has a unique patient identifier to assist in ensuring that there is
no mismatch.
Severe Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis, can occur in patients with known hypersensitivity to the
ingredients in LAVIV. Do not use LAVIV in patients allergic to gentamicin, amphotericin, dimethyl sulfoxide (DMSO), or
material of bovine origin.
Active Infection
Injecting LAVIV into areas with skin infections can lead to local or systemic infection.

LAVIV SIDE EFFECTS
The most common Laviv adverse side effects, occurring in ≥ 1% of patients who received LAVIV, were injection-site
redness, bruising, swelling, pain, hemorrhage, edema, nodules, papules, irritation, dermatitis, and pruritus. (6)
Adverse Laviv side effects occurring in fewer than 1% of trial subjects were acne, facial or eyelid edema,
hypersensitivity or decreased skin sensation at the injection site, post-procedural discomfort (headache, toothache, and
jaw pain), herpes labialis, hyperpigmentation at the injection site, injection-site ischemia, basal cell cancer, and
leukocytoclastic vasculitis.

LAVIV WARNINGS AND PRECAUTIONS
Hypersensitivity reactions can occur with LAVIV.
LAVIV can cause bleeding and bruising at the treatment site.
Vasculitis has occurred following treatment with LAVIV.
Herpes labialis has occurred following treatment with LAVIV.
Basal cell cancer has occurred following treatment with LAVIV.
Keloid and hypertrophic scarring may occur following post-auricular skin biopsies or LAVIV injections.
Patients with genetic disorders affecting dermal fibroblasts or formation of normal collagen matrices may have an
abnormal response to LAVIV.
Immunosuppressed patients, or those who undergo chemotherapy for malignancies or receive immunomodulatory
therapies for autoimmune diseases, may have an increased susceptibility to infection and difficulty healing from LAVIV
treatments.
Employ universal precautions when handling LAVIV. Patients undergoing procedures associated with LAVIV are not
routinely tested for adventitious viruses.
Sterility tests are not completed when LAVIV is shipped to the clinic.

Pregnancy: No human or animal data. Use LAVIV only if clearly needed.
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SOURCES:
1. Summary Basis for Regulatory Action, Date: June 20, 2011, BLA/ STN#: 125348/0
2. Highlights of Prescribing Information,
FDA website, November 16, 2011
3. New Facial Filler Available in Miami
NBC Miami, Nov 9, 2011