Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See definition of “accelerated filer and large accelerated filer” in Rule 12b-2 of the Exchange Act. (Check one).
Large accelerated filer o Accelerated filer o Non-accelerater filer o Smaller reporting company x
(do not check if a smaller
reporting company)
Indicate by check mark if the registrant is a shell company (as defined in Rule 12b-2 of the Act). YESo NOx
Aggregate market value of the voting and non-voting common stock held by nonaffiliates of the registrant as of June 30, 2007, was approximately $72,300,000 (based upon the last reported sale price of $1.58 per share on June 30, 2007, on The American Stock Exchange).
There were 65,529,666 shares of common stock outstanding as of March 21, 2008.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the definitive proxy statement for the registrant’s 2008 annual meeting of stockholders to be filed within 120 days after the end of the period covered by this annual report on Form 10-K are incorporated by reference into Part III of this annual report on Form 10-K.
PART I
|
Item 1. |
BUSINESS |
SPECIAL NOTE REGARDING FORWARD LOOKING STATEMENTS
This report contains forward-looking statements within the meaning of Section 27A of the Securities Act, Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act, and the Private Securities Litigation Reform Act of 1995 that are subject to risks and uncertainties. You should not place undue reliance on those statements because they are subject to numerous uncertainties and factors relating to our operations and business environment, all of which are difficult to predict and many of which are beyond our control. These statements often include words such as “may,” “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate” or similar expressions. These statements are based on assumptions that we have made in light of our industry experience as well as our perceptions of historical trends, current conditions, expected future developments and other factors we believe are appropriate under the circumstances. As you read and consider this report, you should understand that these statements are not guarantees of performance results. They involve risks, uncertainties and assumptions. Although we believe that these forward-looking statements are based on reasonable assumptions, you should be aware that many factors could affect our actual financial results or results of operations and could cause actual results to differ materially from those in the forward-looking statements. You should keep in mind that forward-looking statements made by us in this report speaks only as of the date of this report. Actual results could differ materially from those currently anticipated as a result of a number of risk factors, including, but not limited to, the risks and uncertainties discussed under the caption “Risk Factors.” New risks and uncertainties come up from time to time, and it is impossible for us to predict these events or how they may affect us. We have no duty to, and do not intend to update or revise the forward-looking statements in this report after the date of this report. In light of these risks and uncertainties, you should keep in mind that any forward-looking statement in this report or elsewhere might not occur.
Overview
Antares Pharma, Inc. (“Antares,” “we,” “our” or “us”) is a specialized pharma product development and pipeline company with patented drug delivery platforms including Advanced Transdermal Delivery (ATD™) gels, oral disintegrating (Easy Tec™) tablets, disposable pressure assisted auto injection systems (Vibex™), reusable needle-free injection systems (VISION® and Valeo™) and disposable pen injection systems. Two of these platforms have generated FDA approved products. These platforms and products are summarized and briefly described below:
Delivery Platforms
|
Transdermal Drug Delivery Systems |
Advanced Transdermal Delivery (ATD™) |
Systemic or Topical |
|
Oral Disintegrating Tablets |
Easy Tec™ |
|
|
Parenteral Medicines |
Needle-Free Reusable Injectors (MJ Platform) Medi-Jector VISION® and Valeo™ |
|
|
Pressure Assisted Auto Injectors (AJ Platform) Vibex™ |
||
|
Disposable Pen Injectors |
||
|
Vaccine Intradermal Injectors |
||
Products
Transdermal Systems
Our transdermal systems consist of an unique formulation in semisolid
dosage forms (preferably gels) that deliver medication efficiently and minimize
gastrointestinal impact, as well as, the initial liver metabolism effect of some orally
ingested drugs. Our gels are hydro-alcoholic and contain a combination of permeation
enhancers to promote rapid drug absorption through the skin following application
typically to the arms, shoulders, or abdomen. Our transdermal gel systems provide the
option of delivering both systemically (penetrating into and through the subcutaneous
tissues and then into the circulatory system) as well as locally (e.g. topically for
skin and soft tissue injury, infection and local inflammation). Typically, the gel is
administered daily, and is effective on a sustained release basis over approximately a
24-hour period of time. Our gel systems are known as our Advanced Transdermal Delivery
(“ATD™”) gels.
Oral Disintegrating Tablets
Our Easy Tec™ oral disintegrating tablets are designed to help
patients who experience difficulty swallowing pills, tablets or capsules, while
providing the same effectiveness as conventional oral dosage forms. Our tablet features
a “disintegrant addition” that facilitates the disintegration of the oral
drug to promote quick and easy administration in saliva without water. This could play
an important role in our ability to target the pediatric, geriatric and analgesic
markets. We believe that the ability of Easy Tec™ tablets to be manufactured
without specialized equipment and their non-effervescent (highly moisture sensitive)
qualities represents several significant processing and packaging advantages over
conventional competitors. Our Easy Tec™ tablets may also be of interest to
pharmaceutical firms seeking line extensions in the marketplace. There may also be
further benefits if Easy Tec™ can be formulated with certain actives to provide
buccal absorption.
Pressure Assisted Injection Devices
Our injection device platform features four distinct products: reusable
needle-free injectors, disposable pressure assisted auto injectors, disposable pen
injectors and vaccine intradermal injectors. Each is briefly described
below:
•
Reusable needle-free injectors
deliver precise medication doses through high-speed,
pressurized liquid penetration of the skin without a needle. These
reusable, variable-dose devices are engineered to last for two years
and are designed for easy use, facilitating self-injection with a
disposable syringe to assure safety and efficacy. The associated
sterile plastic disposables, needle-free syringes and adapters are
designed for use as appropriate for the drug and indication.
We have sold the Medi-Jector VISION® for use in more than
30 countries to deliver either insulin or human growth hormone (“hGH”). The
Medi-Jector VISION® employs a disposable plastic needle-free syringe,
which offers high precision liquid medication delivery through an opening that is
approximately half the diameter of a standard, 30-gauge needle. The product is
available over-the-counter (“OTC”) or by prescription in the United States
for use by patients with diabetes, and available through our partners in Europe, Japan
and Asia for hGH. To date, we believe that more than 100 million such injections have
been performed worldwide.
•
Disposable pressure assisted auto injectors
(“Vibex™”) employ the same
basic technology developed for the Medi-Jector VISION®,
a controlled pressure delivery of drugs into the body utilizing a
spring power source. Combining pressure with a tiny hidden needle
supports the design of a disposable, single-use injection system
compatible with conventional glass drug containers. The Vibex™
system is designed to economically provide highly reliable fast
subcutaneous injections with minimal discomfort and improved
convenience in conjunction with the enhanced safety of a shielded
needle. After use, the device can be disposed of without the typical
“sharps” disposal concerns. We and our potential partners
have successfully tested the device in multiple patient preference
studies. We continue to explore product extensions within this
category, including the targeting of various body sites and devices
with multiple dose, variable dose and user-fillable
applications.
•
Disposable pen injectors
are needle-based devices designed to deliver multiple
injections from multi-dose drug cartridges. The devices contain
mechanisms that specify the dose to be delivered by defining the amount
of movement by the stopper in the cartridge with each device actuation,
similar to dose control mechanisms in the Medi-Jector
VISION®. In contrast to the VISION®
reusable needle-free injectors, the cartridge drug container
is integral to the pen injector and after utilizing all the drug from
the cartridge, the entire device is then disposed.
•
Vaccine intradermal injectors
are a variation of the Vibex™ disposable pressure
assisted auto injection technology and are being developed to deliver
vaccines into the dermal and subdermal layers of the skin (a preferred
site of administration in the vaccine industry). We believe that this
proprietary device will offer easier and more rapid dosing compared
with conventional needle-based devices.
History
On January 31, 2001, we (Antares, formerly known as Medi-Ject
Corporation or “Medi-Ject”) completed a business combination to acquire the
three operating subsidiaries of Permatec Holding AG (“Permatec”),
headquartered in Basel, Switzerland. The transaction was accounted for as a reverse
acquisition, as Permatec's shareholders initially held a majority of the outstanding
stock of Antares. Medi-Ject was at that time, focused on delivering drugs across the
skin using needle-free technology, and Permatec specialized in delivering drugs across
the skin using transdermal patch and gel technologies as well as developing oral
disintegrating tablet technology. With both companies focused on drug delivery but with
a focus on different sectors, it was believed that a business combination would be
attractive to both pharmaceutical partners and to our stockholders. Upon completion of
the transaction our name was changed from Medi-Ject Corporation to Antares Pharma,
Inc.
Our Parenteral Medicines (device) division is located in Minneapolis,
Minnesota, where we develop and manufacture with partners novel pressure assisted
injectors, with and without needles, which allow people to self-inject drugs. We make a
reusable, needle-free, spring-action injector device known as the Medi-Jector
VISION®, which is legally marketed for use with insulin and human growth
hormone. Using an adapter, the liquid drug is drawn from a conventional vial into the
plastic needle-free syringe, through a small hole at the end of the syringe. When the
syringe is held against an appropriate part of the body and the spring is released, a
piston drives the fluid stream into the tissues beneath the skin, from where the drug
is dispersed into systemic circulation. A person may re-arm the device and repeat the
process or attach a new sterile syringe between injections. We have had success in
achieving distribution of our device for use with human growth hormone through licenses
to pharmaceutical partners, and it has resulted in continuing market growth and, we
believe, a high degree of customer satisfaction. Distribution of growth hormone
injectors occurs in Europe, Japan and other Asian countries through our pharmaceutical
company relationships.
We have also developed variations of the needle-free injector by adding
a very small hidden needle to a pre-filled, single-use disposable injector, called the
Vibex™ pressure assisted auto injection system. This system is an alternative to
the Vision® system for use with unit dose injectable drugs and is
suitable for branded and branded generic injectables. Recently we also developed a
disposable multi-dose pen injector for use with standard multi-dose cartridges. We have
entered into multiple licenses for these devices mainly in the U.S. and Canada with
Teva Pharmaceuticals.
Our Pharma division is located in Basel, Switzerland, where we develop
pharmaceutical products utilizing our transdermal systems. Our first transdermal and
oral disintegrating tablet products were developed under Permatec’s name in the
mid-1990s. Permatec’s research efforts moved away from the transdermal patch
field and focused on transdermal gel formulations, which allow the delivery of
estrogens, progestins, testosterone and other drugs in a gel base without the need for
occlusive or potentially irritating adhesives. Several licensing agreements with
pharmaceutical companies of various sizes have led to successful clinical evaluation of
our formulations. In 2006 the FDA approved our first transdermal gel product for the
treatment of vasomotor symptoms in post-menopausal women. We are also developing our
own transdermal gel-based products for the market and have initiated a pivotal safety
and efficacy trial for Anturol™, our oxybutynin transdermal gel product for
overactive bladder.
We believe that our transdermal gels minimize first pass liver
metabolism, gastro intestinal effects and skin erythema. Other advantages include
cosmetic elegance and ease of application as compared to transdermal patches and have
potential applications in such therapeutic markets as hormone replacement, overactive
bladder, osteoporosis, cardiovascular, pain management and central nervous system
therapies. We also believe that our proprietary ODT tablets can enable delivery of
certain drugs orally in the area of opioid analgesia and nonsteroidal anti-inflammatory
drugs.
We operate in the specialized drug delivery sector of the pharmaceutical
industry. Companies in this sector generally leverage technology and know-how in the
area of drug formulation and product development to pharmaceutical manufacturers
through licensing and development agreements while continuing to develop their own
products for the marketplace. We also view many pharmaceutical and biotechnology
companies as collaborators and primary customers. We have negotiated and executed
licensing relationships in the needle-free devices segment in the U.S., Europe and
Asia, the auto injector segment in the U.S. and Canada, the transdermal gels segment
(several development programs in place worldwide, including the United States and
Europe) and the Easy Tec™ ODT segment worldwide. In addition, we continue to
market our re-usable needle-free devices for the self administration of insulin in the
U.S. market through distributors and have licensed our technology in the diabetes and
obesity fields.
We are a Delaware corporation. Principal executive offices are located
at Princeton Crossroads Corporate Center, 250 Phillips Boulevard, Suite 290, Ewing, New
Jersey 08618; telephone (609) 359-3020. We have wholly-owned subsidiaries in
Switzerland (Antares Pharma AG and Antares Pharma IPL AG) and the Netherland Antilles
(Permatec NV).
Industry Trends
Based upon experience in the industry, we believe the following
significant trends in healthcare have important implications for the growth of our
business.
When a drug loses patent protection, the branded version of the drug
typically faces competition from generic alternatives. It may be possible to preserve
market share by altering the delivery method, e.g., a single daily controlled release
dosage form rather than two to four pills a day. We expect branded and specialty
pharmaceutical companies will continue to seek differentiating drug delivery
characteristics to defend against generic competition and to optimize convenience to
patients. The altered delivery method may be an injection device or a novel oral or
transdermal formulation that may offer therapeutic advantages, convenience or improved
dosage schedules. Major pharmaceutical companies now focus on life cycle management of
their products to maximize return on investment and often consider phased product
improvement opportunities to maintain competitiveness.
Major pharmaceutical companies market directly to consumers and
encourage the use of innovative, user-friendly drug delivery systems, offering patients
a wider choice of dosage forms. We believe the patient-friendly attributes of our
transdermal gels, ODT tablets and injection technologies meet these market
needs.
We believe transdermal gel formulations offer patients more choices and
added convenience with no compromise of efficacy. Our ATD™ gel technology is
based upon so-called GRAS (“Generally Recognized as Safe”) substances,
meaning the toxicology profiles of the ingredients are known and widely used. We
believe this approach has a major regulatory benefit and may reduce the cost and time
of product development and approval.
Other industry trends include the increasing difficulty in getting drugs
approved by the FDA as well as the continuing need to demonstrate long term safety thus
resulting in longer time lines to approval. Thus dosing and specifically minimum
effective dose is becoming an ever increasing trend.
Many drugs, including selected hormones and protein biopharmaceuticals,
are degraded in the gastrointestinal tract and may only be administered through the
skin, the lungs or by injection. Pulmonary delivery is complex and has recently been
commercialized for limited therapeutic proteins intended for systemic delivery.
Injection therefore remains the mainstay of protein delivery. The growing number of
protein biopharmaceuticals requiring injection may have limited commercial potential if
patient compliance with conventional injection treatment is not optimal. The failure to
take all prescribed injections can lead to increased health complications for the
patient, decreased drug sales for pharmaceutical companies and increased healthcare
costs for society. In addition, it is becoming increasingly recognized that
conventional needles and syringes are inherently unreliable and require special and
often costly disposal methods. Industry expectations are that improvements in protein
delivery systems will continue to be accepted by the market.
In addition to the increase in the number of drugs requiring
self-injection, recommended changes in the frequency of injections may contribute to an
increase in the number of self-injections. Biosimilar drug legislation
continues to gather momentum in Congress. In order to differentiate
biosimilars, novel patented delivery systems are becoming more important to extend
product proprietary position as well as secure patient preference.
The importance of vaccines in industrialized and emerging nations is
expanding as the prevalence of infectious diseases increases. New vaccines and improved
routes of administration are the subject of intense research in the pharmaceutical
industry and we have been researching the feasibility of using our devices for vaccines
and new vaccine ingredients including evaluating opportunities in bio-terrorism
initiatives.
Patented pharmaceutical products continue to be challenged by generic
companies once substantial proprietary sales are generated. All of our proprietary
delivery systems may provide pharmaceutical companies the ability to protect and extend
the life of a product.
Market Opportunity
According to a February 2008 Thomson Pharma Drug Report, the worldwide
market for urinary incontinence was $1.9 billion in 2006 and is estimated to be $3.1
billion by 2011. Older incontinence drugs, such as oral oxybutynin, are plagued by
anticholinergic effects including moderate to severe dry mouth, constipation and
somnolence. In a 2006 Cowen & Co. publication it was estimated that half of the 20
million U.S. adults suffering from overactive bladder either are too embarrassed to
discuss the symptoms or are not aware that pharmacological treatment is available. It
was further estimated that only 47% of U.S. incontinence patients sought treatment in
2005 and that 16% of incontinence patients were compliant with their treatment in 2005
estimated to increase to only 18% by 2010.
According to a February 2008 Thomson Pharma Drug Report, the worldwide
hormone replacement market is expected to grow from $1.9 billion in 2006 to $2.1
billion by 2011. Further growth in this sector may be achieved by the use of
testosterone products in both male and female applications. According to a
comprehensive study by Cowen & Co. in 2006, the female sexual dysfunction
(“FSD”) market is estimated to be 78 million sufferers worldwide rising to
95 million by 2010. Additionally, the worldwide sexual dysfunction market is projected
to grow to $5.6 billion by 2010. The importance of gel products containing
testosterone for men has been exemplified with the success of Androgel®
(Unimed-Solvay) and Testim® (Auxilium Pharmaceuticals) for treatment of male
hypogonadism, where combined sales were recently estimated at approximately $500
million per year. A new market opportunity also exists with the use of low dose
testosterone for treatment of FSD, a disorder according to published reports that
affects an estimated 40-55% of all women and for which no drug is currently approved in
the U.S. Antares Pharma, along with its U.S. partner BioSante, has a low dose
testosterone product named Libi-Gel™, which has completed Phase II testing for
FSD and is currently in Phase III clinical trials. We have the exclusive market rights
in Europe and elsewhere outside the United States for Libi-Gel™. As evidenced in
Europe we believe that patient demand for transdermal hormone therapy products will
continue to increase. Evidence of this belief is the recent commercial launch, in
France, Italy, Spain, U.K., Germany and others, by Proctor and Gamble of the
Intrinsa® Patch, a testosterone transdermal patch for FSD. Gel products are also
being formulated to address equally large opportunities in other sectors of the
pharmaceutical industry, including cardiovascular, pain, infectious diseases, addiction
and central nervous system therapies.
The central nervous system ("CNS") consists of the brain and spinal
cord. Disorders of this system are many, varied and frequently severe, affecting a
large portion of the population. These debilitating disorders include diseases such as
Parkinson’s disease, restless leg syndrome, epilepsy and migraine and psychotic
disorders such as anxiety, bipolar disorder, depression and schizophrenia. In addition,
chronic pain is a neurological response to disease or injury; or it may have no readily
apparent cause. Regardless of the cause, chronic pain can have devastating effects on
those suffering from it.
Current treatments for CNS disorders vary in effectiveness, but there
are many conditions for which there are few safe and effective drugs. It has been
estimated that nearly $36 billion is spent annually on prescription CNS drugs.
According to Wolters Kluwer Health data, the total US market for pain management
pharmaceuticals, excluding over-the-counter products, totaled in excess of $20 million
in 2007. Many CNS and chronic pain drugs merely treat the symptoms and do not provide
cures. According to the World Health Organization, diseases of the CNS will constitute
an increasing medical need this century, attributable to an exponential increase of
these diseases after the age of 65 combined with an aging population.
Our parenteral/device focus is specifically on the market for delivery
of self-administered injectable drugs. The largest and most mature segments of this
market consist of insulin for patients with diabetes and human growth hormone for
children with growth retardation. According to a February 2008 Thomson Pharma Drug
Report, the worldwide insulin market is estimated to go down from $8.9 billion in 2006
to $7.9 billion in 2011, however new non-insulin related treatments for diabetes are
expected to expand the market for diabetic products. We believe that the number of
injections will increase with time as the result of new diabetes management techniques,
which recommend more frequent injections.
We believe that a significant portion of needles and syringes that are
used for the administration of drugs could be replaced with user friendly injectors
promoting better compliance and decreasing sharps concerns, but only a small percentage
of people who self-administer drugs currently use needle-free/auto injector systems. We
believe that this lack of market penetration is due to older technology not meeting
customer needs owing to cost and performance limitations as well as the small size of
the companies directly marketing to consumers not being able to gain a significant
“share of voice” in the marketplace. We believe that our technology
overcomes most of these limitations of the past and that our business model of working
with pharmaceutical company partners has the potential for improved market penetration.
Further, we anticipate developing our own pharmaceutical products using our pressure
assisted auto injectors in the future.
According to a February 2008 Thomson Pharma Drug Report, the worldwide
hGH market in 2006 was estimated at $2.4 billion. Our pharmaceutical partner in Europe,
Ferring Pharmaceuticals BV (“Ferring”), has made significant inroads using
our injectors in the hGH market, and we expect similar progress in other geographic
regions where partnerships have already been established. Other injectable drugs that
are presently self-administered and may be suitable for injection with our systems
include therapies for the prevention of blood clots and the treatment of multiple
sclerosis, migraine headaches, inflammatory diseases, impotence, infertility, AIDS and
hepatitis. We also believe that many injectable drugs currently under development will
be administered by self-injection once they reach the market. This is supported by the
continuing development of important chronic care products that can only be given by
injection, the ongoing effort to reduce hospital and institutional costs by early
patient release, and the gathering momentum of new classes of drugs that require
injection. A partial list of such drugs introduced in recent years that all require
self injection include Enbrel® (Amgen, Wyeth) for treatment of rheumatoid
arthritis, Aranesp® (Amgen) for treatment of anemia, Kineret® (Amgen) and
Humira® (Abbott) for rheumatoid arthritis, Forteo™ (Lilly) for treatment of
osteoporosis, Intron® A (Schering Plough) and Roferon® (Roche) for hepatitis C,
Lantus® (Aventis Pharma) and Byetta® (Lilly) for diabetes, Rebif® (Serono)
for multiple sclerosis, Copaxone® (Teva) for multiple sclerosis and Gonal-F®
for fertility treatment.
Products and Technology
We are leveraging our experience in drug delivery systems to enhance the
product performance of established drugs as well as new drugs in development. Our
current technology platforms include transdermal Advanced Transdermal Delivery
(ATD™) gels; oral disintegrating tablets (Easy Tec™); disposable pressure
assisted auto injection systems (Vibex™); disposable pen injection systems; and
reusable needle-free injection systems (Medi-Jector VISION® and
Valeo™).
TRANSDERMAL DRUG DELIVERY
Transdermal drug delivery has emerged as a generally safe and
patient-friendly method of drug delivery. The commercialization of transdermal products
for controlled drug delivery began over two decades ago. In more recent years
transdermal gels, creams and sprays have become increasingly more popular as
alternative delivery systems. Among transdermal products currently marketed are
nitroglycerin for angina, scopolamine for motion sickness, fentanyl for pain control,
nicotine for smoking cessation, estrogen for HT, clonidine for hypertension, lidocaine
for topical anesthesia, testosterone for hypogonadism, and a combination of estradiol
and a norelgestimate for contraception. Skin penetration enhancers are often used to
enhance drug permeation through the dermal layers.
The primary goal of transdermal drug delivery is to effectively
penetrate the surface of the skin via topical administration. When successful,
transdermal drug delivery provides an easy and painless method of administration. The
protective capabilities of the skin, however, often act as a barrier to effective
delivery. Since the primary role of the skin is to provide protection against infection
and physical damage, the organ can prevent certain
pharmaceuticals from entering the body as well. As a result, a limited
number of active substances are able to cross the skin’s surface.
Despite these limitations, transdermal drug delivery is still viewed as
a highly attractive route of administration for certain therapeutics. As a high
concentration of capillaries is located immediately below the skin, transdermal
administration provides an easy means of access to systemic circulation. Transdermal
systems can be designed to minimize absorption of the active drug in the blood
circulation as is needed in topical applications. This allows a build-up of drug in the
layers underlying the skin, leading to an increased residence time in the targeted
tissue. Transdermal systems can also be designed to release an active ingredient over
extended periods of time, providing benefits similar to depot injections and implants,
without the need for an invasive procedure. If required, patients are also able to
interrupt dosing by removing a patch or discontinuing the application of a gel.
Finally, this delivery technology typically minimizes first-pass metabolism by the
liver as well as many of the gastrointestinal concerns of many orally ingested
drugs.
Transdermal Gels
While transdermal patches remain an important aspect of the transdermal
drug delivery market, transdermal gels have recently emerged as a viable means of
administering an increasingly wide array of active pharmaceutical treatments. The
concept of transdermal gels parallels that of the transdermal patch in the creation of
a drug reservoir to provide sustained delivery of therapeutic quantities of a drug.
While a patch provides this from an external reservoir, gel formulations typically
create a subdermal reservoir of the medication. Transdermal patches, however, have
recently resulted in increasingly more adverse events, specifically skin irritation
events associated principally with the occlusive nature of patches
and the use of adhesives that contain residual solvents and irritant
monomers. Most of these factors are minimized in transdermal gels.
Gels also provide drug developers with an opportunity to explore a wide
variety of potential applications. Due to the physicochemical properties of the
excipients employed in gels, combined with the enhanced solubilization properties, a
broad range of active agents can be formulated. These solubilization properties allow
for higher concentrations of the active ingredient to be incorporated for delivery. The
enhanced viscosity in gels further enhances the patient’s ability to apply the
product with little-to-no adverse cosmetic effect. There is also relatively little
limitation in the surface area to which a gel can be applied, as opposed to patches,
allowing greater quantities of drug to be transported if required.
We have developed our ATD™ gel technology that utilizes a
combination of permeation enhancers to further bolster a pharmaceutical agent’s
ability to penetrate the skin, which leads to a sustained plasma profile of the active
agent, without the skin irritation and cosmetic concerns often associated with
patches.
Advanced Transdermal Delivery (ATD™) System
Our ATD™ system successfully penetrates the skin to deliver a
variety of treatments. The gels consist of a hydro-alcoholic base including a
combination of permeation enhancers. The gels are also designed to be absorbed quickly
through the skin after application typically to the arms, shoulders, or abdomen and
release the active ingredient into the blood stream predictably over approximately a 24
hour period of time. The following is a summary of the competitive advantages of our
ATD™ gel system:
Competitive Advantages of ATD™ Gel
System
•
Discrete
•
Easy application
•
Cosmetically appealing compared with patches
•
Reduced skin irritancy compared with patches
•
Application of once per day for most products
•
Potential for delivery of larger medication
doses
•
Potential for delivery of multiple active
drugs
•
Ability to be either systemic or topical
Our ATD™ gels can deliver both a single active ingredient as well
as a combination of active ingredients with different release profiles, and have
demonstrated potential in a variety of therapeutic areas. One of our licensed gels, an
estrogen gel for women to treat vasomotor symptoms associated with menopause called
Elestrin®, was approved by the FDA in December 2006 and commercially
launched in mid-2007. In addition, we have signed a development and license agreement
for a gel product based on our ATD™ system that is being developed to treat a
central nervous system (“CNS”) disorder. Other current ATD™ drug gels
in development encompass an oxybutynin gel for treatment of overactive bladder
(Anturol™), a low dose testosterone gel to treat low libido in women
(Libi-Gel™), a contraceptive gel, another CNS product (AP1126) and an alprazolam
gel for anti-anxiety. We have also licensed an ibuprofen gel in 11 countries.
ATD™ gels may be extended to a variety of fields, including the treatment of
cardiovascular disease and chronic pain, in which potent compounds may require
alternatives to oral and injectable delivery for the following reasons:
•
poor oral uptake;
•
high first-pass liver effect;
•
requirement for less frequent administration;
•
desire to provide an alternative dosage form;
•
reducing peak plasma levels to avoid side effects;
and
•
reduction in gastrointestinal side effects.
We have also formulated several combination gels demonstrating the
ability to deliver multiple actives with different release profiles.
ORAL DRUG DELIVERY
The majority of all drugs are administered orally. Despite this, there
remain limitations for those patients who have difficulty swallowing conventional oral
dosage forms or where an underlying disease state (for example, migraine, Parkinsonism
or cancer) impacts a person’s ability to swallow. Additionally, where patients
are resistant to oral drug delivery, the phenomenon of “cheeking” (hiding a
pill between the cheek and gum) and subsequent drug disposal is quite well known. New
generations of oral product forms are being developed to address these
issues.
Oral Disintegrating Tablets
Fast-dissolving tablet technology is an oral delivery method that offers
an alternative to patients who experience difficulty ingesting conventional oral dosage
forms. As a result, formulators are focusing on the development of tablet dosage
formulations for oral administration that dissolve rapidly in saliva without need for
the patient to drink water. This formulation is easy to take and possesses similar
therapeutic benefits to traditional oral technologies, thus appealing to a wide
demographic population.
One of the primary realities influencing the development of
fast-dissolving technologies is the increased life expectancy of a growing geriatric
population. As many elderly individuals experience difficulty taking conventional oral
dosage forms, such as solutions, suspensions, tablets and capsules, the need for more
user-friendly formulations is expanding. While swallowing difficulties often affect the
elderly population, many young individuals also experience difficulty as a result of
underdeveloped muscular and nervous systems. Other groups, including the mentally ill,
the developmentally disabled and uncooperative patients also require special attention.
Other circumstances, such as motion sickness, allergic attacks and an unavailable
source of water also necessitate fast-dissolving oral formulations.
The development of a fast-dissolving tablet also provides pharmaceutical
companies with an opportunity for product line extensions. A wide range of drugs (e.g.
neuroleptics, cardiovascular drugs, analgesics, antihistamines, and drugs for erectile
dysfunction) may be considered candidates for this technology.
Easy Tec™ Oral Disintegrating Tablets
Our patented Easy Tec™ technology is based on the simultaneous use
of two disintegrants in an oral formulation. We believe two primary advantages of Easy
Tec™ over competing technologies are that Easy Tec™
tablets can be manufactured with conventional tableting equipment and no
unique packaging requirements are necessary. We also believe that Easy Tec™
possesses several other key advantages over competing technologies;
Easy Tec™ Competitive Advantages
•
Higher drug dose loading is possible
•
Friability within pharmaceutical
specifications
•
Moisture sensitivity lower compared with many competitor
products
•
Blister packaging sufficient to prevent moisture
uptake
•
Cost-effective, easy, time-saving process
•
Easily transferable to final product site
•
No specific facility required, compared to effervescent
products
•
Ability to formulate with permeation
enhancers
In addition to being easy to take, such products are perceived as being
fast acting because of rapid dispersion in the mouth. There may also be further
benefits if Easy Tec™ can be formulated with certain actives to provide buccal
absorption. We believe that there may be attractive opportunities to develop our own
ODT products using generic active ingredients as part of our specialty pharmaceutical
strategy and to achieve product approval based on an Abbreviated New Drug Application
(“ANDA”) or 505(b)(2) filing in the United States and equivalent regulatory
submissions in other parts of the world. We have formulated our first Easy Tec™
based product, a non-steroidal anti inflammatory (NSAID) generic currently called
AP-159 for the treatment of pain. Additionally, we have signed a global license
agreement with an unnamed partner in the area of opioid analgesia.
INJECTION DRUG DELIVERY
According to industry sources, an estimated 9-12 billion needles and
syringes are sold each year. While the need for these components will always exist,
burgeoning development efforts are focused on easing the dependence on needles in favor
of more user-friendly injection systems. Currently available data suggest that auto
injectors match the performance of needle and syringe based systems with regard to drug
bioavailability, and offers benefits in the speed and quality of injections as well as
the lack of requirement for needle disposal.
Pressure Assisted Auto Injection
The most significant challenge beyond discovery of new molecules is how
to effectively deliver them by means other than conventional injection technology. The
majority of these molecules have not, to date, been amenable to oral administration due
to a combination of several factors, including breakdown in the gastrointestinal tract,
fundamentally poor absorption, or high first pass liver metabolism. Pulmonary delivery
of these molecules, as an alternative to injections, has also been pursued. It remains
to be seen how clinical success will be accepted by patients, doctors and third party
payers. Many companies have expended considerable effort in searching for less invasive
ways to deliver such molecules that may allow them to achieve higher market acceptance,
particularly for those requiring patient self-administration.
Pressure assisted auto injection is a form of parenteraldrug delivery
that continues to gain acceptance among the medical community. Encompassing a wide
variety of sizes and designs, this technology operates by using pressure to force the
drug, in solution or suspension, through the skin and deposits the drug into the
subcutaneous tissue.
Needle-Free Injectors
Needle-free injection represents a combination of an accepted technology
- injection, with the elimination of the part of the injection – the needle, that
concerns patient’s that have to self administer and health care professionals
concerned about risks to themselves. Improving patient comfort through needle-free
injection may increase compliance and mitigate the problem of daily injections.
Needle-free delivery eliminates the risk of needlestick injuries as well, which occurs
frequently in institutions in the U.S., and can result in disease transmission to
healthcare workers.
One of the primary factors influencing development in the category of
needle-free injection is the inherent problematic dependence on needles. It is also
recognized that greater willingness to accept injection therapy could have a beneficial
impact on disease outcomes. For example, patients with diabetes appear to be reluctant
to engage in intensive disease management, at least in part because of concerns over
increased frequency of injections. Similarly, patients with diabetes who are
ineffectively managed with oral hypoglycemic agents are reluctant to transition to
insulin injections in a timely manner because of injection concerns.
The advent of these technologies has, to date, had a minor influence
within the injectable sector, and they have failed to produce the deep market
penetration that many within the industry believe they are capable of gaining. Several
factors are believed to contribute to this lack of market penetration, beginning with
older needle-free injection systems. Many of the early needle-free injection systems
had an assortment of drawbacks associated with both performance and cost efficiency.
With potential consumers aware of these historical shortcomings, current technologies
promising greater efficiency and lower prices have failed to gain wide acceptance in
the industry.
Medi-Jector VISION®
(MJ7)
The Medi-Jector VISION® has been sold for use in more
than 30 countries to deliver either insulin or human growth hormone. The product
features a reusable, spring-based power source and disposable needle-free syringes,
which eliminate the need for routine maintenance of the nozzle and allow for easy
viewing of the medication dose prior to injection. The device’s primary advantage
over earlier devices is its ease of use and cost efficiency. The product is also
reusable, with each device designed to last for approximately 3,000 injections (or
approximately two years) while the needle-free syringe, when used with insulin or
growth hormone, is disposable after approximately one week when used by a single
patient for injecting from multi-dose vials.
The Medi-Jector VISION® administers injectables by using
a spring to push the active ingredient in solution or suspension through a micro-fine
opening in the needle-free syringe. The opening is approximately half the diameter of a
standard 30-gauge needle. A fine liquid stream then penetrates the skin, and the dose
is dispersed into the layer of fatty, subcutaneous tissue. The drug is subsequently
distributed throughout the body, successfully producing the desired effect.
We believe this method of administration is a particularly attractive
alternative to the needle and syringe for the groups of patients described
below.
Patient Candidates for Needle-Free Injection
•
Young adults and children