As we age, facial tissue loses volume and elasticity resulting in the ageing process we see. Gradually, our skin becomes duller and more irregular and we develop lines and wrinkles. Marks that previously did not matter such as acne scars and open pores become more apparent.

A healthy diet, regular exercise, good skin care, confidence and a positive outlook on life all help us to look good for our age. But, as the years pass, it may be that a little extra help is needed to restore vitality.

In addition to everyday skincare practice including cleansing and moisturising, other options are available to help maintain healthy looking skin There are procedures that relax lines and wrinkles to help slow down formation of permanent marks, others that refill deeper lines and areas that have lost their fullness with time. Other techniques remove the dull outermost layers of skin to encourage new skin layers to develop. The modern approach is based on combining the best options for you as an individual to provide results that help you look and feel good

Skin acts as a tough protective barrier against infection and damage and it also forms a central aspect of our appearance. The strains placed on the skin as it performs its barrier function can eventually affect the living cellular elements of the skin which are responsible for maintaining this complex structure. The cells, called dermal fibroblasts, that make the structural matrix of skin by producing collagen, hyaluronic acid and elastin become depleted and the remaining cells become less active. The result is that this broken down matrix is not replaced in sufficient quantity to maintain skin thickness and tone. There are many skin products that aim to replace some of this lost matrix by injecting collagen or hyaluronic acid and these treatments are suitable for filling large specific lines or wrinkles and instant results are possible. But these corrections do not affect the micro-architecture of the dermis and do not affect the overall tone of the skin.

Advances in science now make it possible to replace the lost dermal fibroblasts themselves by careful injection. This procedure is conducted by a specialised doctor skilled in this approach.

VAVELTA® is based on many years of scientific research and the most up to date knowledge of ageing skin. VAVELTA® is a suspension of human dermal fibroblasts for injection, when injected into the skin they are intended to rejuvenate the structural matrix of the skin.

After being injected, the cells take their time to become established and results are expected to be gradual, subtle and targeted at general skin quality and rejuvenation. The matrix is expected to be produced in the same way that it is naturally produced in the skin and is not, therefore, manufactured or artificial. No other procedure is available that offers this approach of matching your skin’s structure The results may take a number of weeks or even a few months to become apparent, but the beauty of this approach is that the skin should improve gradually as the new cells become integrated and established and have their effect on your own skin structure. The intention is to improve the texture, tone and elasticity of the skin to provide a more youthful appearance.

The fibroblasts used in VAVELTA® are young, high quality, healthy cells from a donor source. The use of new cells is expected to give your skin the best possible chance of rejuvenation. They are grown and extensively tested in a purpose built laboratory licensed by the Human Tissue Authority (HTA) and authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK to manufacture investigational medicinal products for human use.

The manufacturer is Intercytex, a British company which specialises in skin and hair regeneration. This company is at the forefront of advances in research and product development for both medical and aesthetic applications. Experience and knowledge has shown us that fibroblasts do not appear to cause any immune response. More than 200,000 individuals have received donor or “allogeneic” fibroblasts for various medical conditions

The procedure involves a local anaesthetic cream being applied to the identified areas of the face (some practitioners may use an injectable anaesthetic for sensitive areas). The cells are then administered as a series of injections approximately one centimetre apart using a very fine needle. The injection is very shallow to place the cells just under the topmost layer of the skin where they would normally be found. There may be some mild discomfort which is quite usual. The procedure may take up to two hours and afterwards you may have some swelling or redness at the injection sites which will fade over the following days.

More than one treatment will probably be necessary to achieve and maintain the desired result. How long the effects last will depend on the condition of the skin and the way it changes over time as it continues to age.

For advice on the number of administrations and the best areas for injection you should have a detailed discussion with your doctor

FAQ - Vavelta

Why do lines and wrinkles occur and what happens to the skin when it ages?
Lines and wrinkles occur in particular locations on the face, neck and hands in response to repeated muscular action, sagging under the force of gravity, excessive exposure to sun, smoking, heat and cold and chemical agents present in the environment.

Wrinkles are often present in areas of particularly thin skin such as around the eyes, between the nose and corners of the lips or between the eyebrows and in locations which are particularly mobile or are moved repeatedly in the same direction. As skin ages it becomes less cellular, thinner and more prone to fine wrinkles.

What are scars and why do they form?
Scars are formed when the dermis is damaged by accidental trauma, disease or for example skin conditions such as acne or surgery. The body forms new collagen fibres to mend the damage resulting in a scar. These may be produced to excess and in a less organised way, resulting in skin with a different texture and quality than the surrounding tissue.

Some scars have a sunken or pitted appearance when underlying structures supporting the skin (i.e. fat or muscle) are lost. Some surgical and acne scars have this appearance. Scars known as contractures result when scars cross joints or skin creases at right angles and the fibres of the scar shorten. These are common after burns and often result in pain and reduced mobility.

What is the extracellular matrix?
The extracellular matrix of the skin is a complex network of fibrous and non-fibrous materials that contribute to the structure and appearance of the skin. The fibres are mainly formed from collagen and elastin and in between these fibres, can be found a variety of large molecules such as proteoglycans and hyaluronic acid.

The extracellular matrix is synthesised and assembled by cells including fibroblasts and keratinocytes to produce a structure that withstands the mechanical and physical forces imposed on the skin.

What is collagen?
Collagen is made by fibroblasts. It is a tough, insoluble protein found throughout the body in the connective tissues that hold muscles and organs in place.

In the skin, collagen supports the epidermis (the outermost layer of skin) making it durable and elastic. Collagen forms a meshwork of fibres and is a key contributor to the structure and texture of skin. As collagen in the meshwork breaks down, it is replaced and repaired by new collagen secreted by fibroblasts.

With age, the number of fibroblasts declines as does their ability to make collagen. In addition, agents (such as metalloproteases or MMPs) that destroy collagen increase, particularly in response to sun exposure. Chronically sun damaged skin has a lower collagen content compared to skin that has not been exposed to the sun This decline in collagen is exacerbated by a reduction in the skin's ability to repair collagen and as the collagen volume and integrity diminishes the meshwork begins irretrievably to break down. This manifests itself in the form of wrinkles and roughened texture.

What is VAVELTA and what is it used for?
VAVELTA is a suspension of human dermal fibroblasts (skin cells or HDFs) in cell storage medium, for injection into the skin. Fibroblasts are responsible for the production of collagen. Injected into the skin, they are intended to repair and restructure the extracellular matrix. VAVELTA has been designed for use in skin damaged by scarring and the ageing process.

How does VAVELTA work?
VAVELTA introduces collagen-secreting skin cells or human dermal fibroblasts (HDFs) the skin's extracellular matrix, by injection into the dermis. The HDFs may lay down new collagen and other extra cellular matrix within the dermis.

Where can VAVELTA be used?
VAVELTA can be used for skin imperfections and scars caused by illness, trauma or surgery and for facial wrinkles.

What are the restrictions on using VAVELTA?
It should not be given to:
" under 18 years of age,
" who has previously experienced a severe reaction to VAVELTA or is known to be allergic (hypersensitive) to any of its ingredients,
" who is pregnant or planning pregnancy within the next three months
" breast feeding
" taking regular immunosuppressive therapies (e.g. chemotherapy or steroids such as prednisolone)
" with a history of keloids (thick scars)
It must not be given to anyone who is allergic to bovine (cow) or porcine (pig) products as VAVELTA may contain trace amounts of these products. VAVELTA must not be given to anyone allergic to gentamycin or amphoteracin B. as these antibiotics are used in the production process.

What is the minimum/maximum age for patients?
The minimum age for receiving VAVELTA is eighteen and the maximum age will depend on the condition of a patient's skin.

Can VAVELTA be used in a patient who is a heavy smoker/drinker?
Yes, although careful consideration to the implications of lifestyle on the condition of the patients overall health and skin should be a priority.

What is the VAVELTA procedure?
The VAVELTA procedure refers to the specialist technique associated with the administration of VAVELTA. VAVELTA must only be administered by experienced physicians, well-trained in selecting appropriate patients and expert in the use of intradermal injection techniques e.g. plastic surgeons, dermatologists and other doctors who specialise in aesthetic medicine.

VAVELTA is injected directly into the skin using a fine gauge needle, under local anaesthesia. It is a minimally invasive procedure.

Is the procedure painful?
VAVELTA is injected into the skin directly into the area being treated so a local anaesthetic such as lidocaine gel will be administered beforehand to prevent significant discomfort in most patients.

Is VAVELTA available from a general practitioner?
VAVELTA is only available from a small number of highly trained specialists within the UK - members of the VAVELTA Clinical Practice Group. These doctors are all plastic surgeons, dermatologists or specialists in aesthetic medicine.

Is there a list of doctors that are offering VAVELTA?
There are a limited number of medical practitioners who are offering VAVELTA in the UK and only members of the VAVELTA Clinical Practice Group can use the product. A full list of contact details will be made available on the website shortly.

What results can you expect?
Results are dependent on the individual. Where human dermal fibroblastsbegin to lay down collagen within the dermis, VAVELTA may provide a gradual improvement in the quality and texture of the skin. Repeat procedures may be undertaken as required.

How long will any results take to be apparent?
It takes time for the injected cells to start producing collagen and stimulate changes in the extracellular matrix and so the time for any results to appear will vary from patient to patient.

How long does VAVELTA last?
Long term clinical information is not yet available, so it is not possible to say how long any effects will last.

How many times will a patient need VAVELTA?
If patients wish to re-treat an area or treat a new area then a further procedure may be undertaken. It will vary from patient to patient and a qualified practitioner will be able to advise patients appropriately.

What are the possible side effects?
There may be some side effects with VAVELTA, although not everyone experiences them. Very common side effects include immediate pain and discomfort at the injection site; this may be associated with transient redness, swelling, itching and/or tenderness, bruising or skin discolouration lasting for several days.

VAVELTA may also cause a delayed reaction at the injection site commencing approximately one week following injection. This is a relatively frequent event and may include redness, swelling and itching. These symptoms may persist for several days before resolving spontaneously.

There is the very rare risk of a generalised allergic reaction to any of the components of VAVELTA. There is also the theoretical risk of permanent swelling, nodule formation and skin discolouration at the injection site. This type of reaction should be reported immediately.

Will I be able to return to work straight after the procedure?
Patients may need to take a day or so off work immediately after the procedure and should consider whether the possibility of experiencing redness, swelling and itching one week after the procedure will affect their ability to work. Make up can be used as necessary 24-48 hours after the procedure.

How much will VAVELTA cost?
The cost of VAVELTA will vary from patient to patient depending on the area treated, the results required and the patient's own response, which may vary from individual to individual. Please consult your medical practitioner for a more detailed breakdown of costs.

Is VAVELTA on the market; is it being sold?
It is commercially available in the UK to a limited group of specialist physicians and we expect to launch it in other European countries in the future.

Is VAVELTA on the market in the US?
In the future VAVELTA may be available in the US but at the current time it is not available in the US. Further clinical trials carried out IN the US as per FDA requirements will also be required.

Is it possible to distribute VAVELTA in other countries?
Not at the moment. It is only available in the UK via a select group of practitioners. Longer term, it will depend on individual country regulations for cell therapy.

Where do human dermal fibroblasts come from?
The cells are derived from human, neonatal foreskin removed during routine circumcision and freely donated

How many foreskins are required?
One foreskin will be the source of tens of thousands of cell cultures.

Were do the donor cells come from?
The HDFs come from donors in the US.

What are the benefits of using these cells?
An advantage of using donor fibroblasts is that neonatal cells are young and metabolically active. The process of growing and manufacturing these cells can also provide a high quality, "off the shelf" product manufactured to rigorous standards.

Why are the cells not rejected?
Allogeneic (i.e. sourced from an unrelated donor) HDFs behave as though they are autologous (i.e. sourced from and applied to the same person) and typically do not stimulate an immune response. They are described as "immune silent".

Over 200,000 individuals have already been treated with donor or allogeneic fibroblasts for a variety of medical conditions over the last decade without immunological problems.

This position is backed by a number of published papers. This information can be found in The use of allogeneic dermal papilla (DP) fibroblasts in regenerative medicine by Janet Hardin-Young PhD in March 29, 2004

Why aren't the proteins produced by the cells rejected?
The allogeneic fibroblasts that we use for VAVELTA are immune-silent as are the proteins that they produce.

Are the cells free from contamination?
Donors are screened for an extensive number of viral contaminants including HIV-1, HIV-II, hepatitis B and C, HTLV-1, HTLV-2 and West Nile Virus and all screening results must be negative for the cells to be used. An extensive list is available for further information from Intercytex. Regular and rigorous testing and quality control measures are implemented during the multiplication of the fibroblasts to ensure there is no known contamination.

Does VAVELTA contain any bovine products?
VAVELTA contains a minute quantity of fetal bovine serum use in the growth process. If a patient is known to be allergic to bovine products, they should not be given VAVELTA.

Have the cells in VAVELTA been modified in any way?
Although the cells are cultured in media, they are not engineered or changed in any way.

Could these cells become cancerous or cause other negative medical outcomes?
There have been no apparent issues with the use of a marketed skin substitute for leg ulcers where over 200,000 administrations of HDFs have taken place without evidence of problems of this kind.

What is the clinical evidence to support the use of this treatment?
A Phase I trial, consisting of a placebo-controlled safety and tolerability study in ten healthy volunteers, was completed. Each subject received a course of three injections given into the skin of the upper arm. VAVELTA was shown to be very well tolerated; no serious adverse events were reported and all adverse events were transient and resolved without treatment.

A Phase II dose-escalation trial of VAVELTA in nasolabial folds has now been completed. In this trial six subjects received a low dose of product. A second group of ten subjects was then treated with a higher dose expected to be used in the final product. All subjects have been followed out to six months post-treatment with the following results to date:
" Wrinkle severity scores improved by at least one grade in 12/16 (75%) patients
" Mean investigator satisfaction score 7.6/10
" Range 4.4-9.8, median 7.8
" Mean patient satisfaction score 7.8/10
" Range 1.5-10, median 8.5

A second Phase II trial for the use of VAVELTA has been completed in ten subjects with acne, varicella and other scarring who have been followed out to six months post-treatment with the following results to date:
" Investigator satisfaction score
" Mean 6.3
" Median 6.2 (range 5.1-7.4)
" Subject satisfaction score
" Mean 6.8
" Median 6.6 (range 4.6-8.5)
No serious adverse events or unexpected adverse events have been observed in either study.

How many patients have received VAVELTA?
More than 50 patients have received VAVELTA for a range of indications including post peel scarring, contractures, facial rejuvenation, acne scarring and a range of other scar types.

What are the other potential uses of VAVELTA?
Human dermal fibroblasts have already been used in the treatment of chronic wounds such as venous leg ulcers and diabetic foot ulcers and are in clinical studies for a wide number of indications, including burns contractures and to replace skin and promote healing.

What are the regulatory guidelines surrounding the marketing and use of VAVELTA?
VAVELTA is regulated under Directive 2004/23/EC on setting the standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells.

As such, Intercytex, the company that invented VAVELTA, is licensed by the Human Tissue Authority.

VAVELTA is also regulated as a "tissue engineered product" in Europe.

Under the Advanced Therapies Regulation, which came into force on 30 December 2007 and will apply from 30 December 2008, tissue engineered products will ultimately be regulated as medicinal products. However, tissue engineered products already on the European Community market on 30 December 2008 have until 30 December 2012 before they have to comply with the medicines regulatory framework.

It has been claimed that the UK has become a "testing ground for untrialled medicines", has VAVELTA been appropriately studied prior to launch in the UK?
The regulation of healthcare products is a complicated and evolving. The pilot clinical studies completed to date suggest that VAVELTA is well tolerated but further studies in larger groups are required to confirm these results. No unexpected adverse effects have been reported and those that occurred were transient and resolved without treatment. The efficacy shown to date indicates that VAVELTA is worthy of further clinical examination. VAVELTA is only available to a small number of suitably qualified physicians within a clinical practice group, applications to be a member of this group can be made to Intercytex. Further clinical studies are also ongoing. The company is taking a very ethical and responsible approach to the development and marketing of VAVELTA.

Is there a procedure for patients and doctors who have queries about VAVELTA?
Intercytex has a dedicated Customer Services team in place to handle a wide range of enquiries (supply, invoicing and medical training etc)

Will there be a training programme for those who wish to offer VAVELTA?
Intercytex will be providing extensive training to strictly qualified medical practitioners who already practice aesthetic medicine: dermatology, plastic/reconstructive surgery.

Is VAVELTA a type of mesotherapy?
No. Mesotherapy is a non-surgical treatment using multiple injections of pharmaceutical or homeopathic medications, plant extracts, vitamins, and other ingredients into the subcutaneous fat. VAVELTA uses live skin cells injected into the dermis.

Is VAVELTA the same as Isolagen?
VAVELTA is quite distinct from Isolagen, because it uses donor cells not the patient's own cells. It is therefore available "off the shelf" and does not require a patient biopsy or the specialised storage of a patient's cells. A further advantage of using donor cells is that these "neonatal" cells are very young and active, which may increase the chance of laying down collagen into the skin tissues.

Can patients who have had Isolagen have VAVELTA?
Yes. Donor cells are used instead of the patient's own cells. In other words, a sample of the patients' cells is not required. At the current time we are advising a gap of a year after the last treatment with Isolagen. Advice should be sought from a member of the Clinical Practice Group.

Why is VAVELTA different from Isolagen?
VAVELTA is different to Isolagen in that it uses donor cells (i.e. it is allogeneic) and not the patient's own cells (autologous). It is therefore more readily available "off the shelf" and does not require a patient biopsy and the specialised storage of patients' cells with linked quality control implications. A further advantage of using donor fibroblasts is that very young, neonatal cells are used, which may increase the chance of laying down collagen into the skin tissues.

Can Intercytex succeed when Isolagen withdrew from the UK?
Intercytex is a different company, with different research and development, manufacturing and supply chain capabilities and a highly credible and experienced management team. The company believes that it will be able to deliver well tolerated and effective products as a result. Intercytex has a number of cell based products in development for the regeneration of skin and hair based on many years experience of growing these cells and developing products that are now available worldwide.

Please visit www.intercytex.com to learn more about Intercytex and the clinical development programme.

What are the differences between VAVELTA and fillers?
Fillers such as hyaluronic acid are designed to treat specific lines and wrinkles and replace lost volume and their effects can last from three to six months. For facial use, VAVELTA introduces human dermal fibroblast into the extracellular matrix with the aim of laying down new collagen within the dermis. Fibroblasts produce extra cellular matrix components that form the basis of new skin, induce additional fibroblasts from surrounding tissues to migrate into the area and produce enzymes and inhibitors to remove debris and remodel tissue

What is the difference between VAVELTA and BOTOX (VISTABEL)?
BOTOX gives the appearance of rejuvenation by the relaxation of the skin's underlying musculature and its effects can last from three to six months but it does not reverse the changes in the extracellular matrix.

VAVELTA is a suspension of live HDFs which may lay down new collagen within the dermis and a may even stimulate the existing fibroblasts to increase collagen production. Its effects can be longer-lasting and are aimed at improving the texture and quality of the skin.

May I have VAVELTA if I already have been using fillers or BOTOX?
Yes, but patients are advised to wait twelve months after having filler in the exactly the same locality. A member of the Clinical Practice group will be able to advise on the treatments had previously and required results.