`Than or Equal to 15 Mg May Be Overcome with Subcutaneous
`Administration
`
`Antares Pharma Announces the Publication of a Head-to-Head, Randomized,
`Crossover Study of Oral versus Subcutaneous Methotrexate in Patients with
`Rheumatoid Arthritis
`
`April 17, 2014 07:00 AM Eastern Daylight Time
`
`EWING, N.J.--(BUSINESS WIRE)--Antares Pharma, Inc. (NASDAQ: ATRS) today announced that the Annals of the
`Rheumatic Diseases has published results from an open-label, head-to-head randomized, crossover study comparing
`the relative bioavailability, safety and tolerability of OTREXUP to oral methotrexate (MTX) in adult patients with
`rheumatoid arthritis (RA).
`
`In this multicenter, three-way crossover study, patients greater than or equal to 18 years old with adult RA undergoing
`treatment with MTX for three months or more were assigned to receive one of four dose levels of OTREXUP, 10 mg, 15
`mg, 20 mg, and 25 mg weekly in a random sequence of three treatments: oral, subcutaneous into the abdomen and
`subcutaneous into the thigh. For 24 hours after the administration of each treatment, blood samples were collected to
`measure drug levels and injection sites were assessed. Forty-seven patients completed the study and the results
`showed that the systemic availability of methotrexate following oral dosing plateaus at 15 mg and greater. Following
`administration of OTREXUP, the systemic availability increased proportionally at every dose, which extended the range
`of exposure compared to patients receiving oral therapy. No unexpected adverse events were noted for either
`formulation in this short term study and higher systemic MTX exposure was not associated with increases in adverse
`events.
`
`“The study results show for the first time that plasma levels of oral dosed MTX are no greater for 20 mg or 25 mg doses
`than for 15 mg doses,” said Michael H. Schiff, M.D., Clinical Professor of Medicine in the Rheumatology Division at the
`University of Colorado School Of Medicine in Denver. “If a patient fails to respond to 15 mg of MTX orally, it may be more
`effective to switch to a subcutaneous regimen rather than continue to raise the oral dose. These findings may have
`implications on future prescribing habits of specialists.”
`
`Historically, parenteral MTX use has been limited in clinical practice for several reasons including the inconvenience of
`weekly injections by a healthcare professional, and/or the challenges associated with teaching patients with impaired
`hand function, safe, sterile and precise self-injection techniques. To address these issues, an easy to use, single-use
`MTX auto injector (OTREXUP) was developed to optimize the clinical benefit of MTX, potentially leading to cost effective
`treatment outcomes.
`
`Medac Exhibit 2006
`Koios v. Medac
`IPR2016-01370, Page 00001
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`Paul K. Wotton, Ph.D., President and Chief Executive Officer, stated, “The publication of this data by the Annals of the
`Rheumatic Diseases adds further validation to the value proposition of OTREXUP.” He continued, “The parenteral
`administration of methotrexate is an accepted treatment method for extending the use to higher doses. We believe
`OTREXUP provides not only greater bioavailability, but more precise, hygienic and greater dosing flexibility for RA
`patients.”
`
`The article can be accessed using the following link: http://ard.bmj.com/cgi/content/full/annrheumdis-2014-205228
`
`IMPORTANT SAFETY INFORMATION (ABBREVIATED)
`
`Otrexup (methotrexate) injection, for subcutaneous use
`
`Otrexup can cause serious side effects that can lead to death, including:
`
`An increased risk of death from organ toxicity. Types of organ toxicity can
`include: gastrointestinal, bone marrow, liver, immune system, nerve, lung,
`kidneys and skin.
`Women who are pregnant are at increased risk for death of the baby and birth
`defects. Women who are pregnant or who plan to become pregnant must not take
`Otrexup. Contraception should be used by both females and males while taking
`Otrexup. For males, pregnancy should be avoided for a minimum of 3 months after
`treatment with Otrexup, and for females, for at least 1 menstrual cycle after treatment.
`Do not take Otrexup if you:
`
`Are pregnant or planning to become pregnant
`Are breastfeeding
`Have alcohol problems
`Have liver problems
`Have problems fighting infection
`Have a blood disorder
`Have an allergy to methotrexate
`Possible side effects of Otrexup
`
`Fertility problems
`Certain cancers
`Tissue and bone problems
`Common side effects of Otrexup include: nausea, stomach pain, indigestion, mouth sores, and rash.
`
`You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call
`1-800-FDA-1088. For more information, go to www.Otrexup.com or call 1-855-OTREXUP (1-855-687-3987).
`
`
`About Vibex Auto Injectors
`
`
`The Vibex Auto Injector is a single-dose, disposable pressure assisted auto injector designed to provide a fast, safe and
`
`time-efficient method of self-injection. The Vibex system features a triggering collar that shields the needle from view.
`The patented retracting collar springs back and locks in place as a protective needle guard after the injection, making
`the device safe for general disposal. Encompassing a wide variety of sizes and designs, this technology operates by
`using pressure to force the drug, solution or suspension through the skin and deposit the drug into the subcutaneous
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`tissue. Our proprietary Vibex disposable auto injector systems combine a low-energy, spring-based power source with a
`®
`shielded needle designed to deliver the needed drug solution. Vibex Auto Injectors are designed, developed and
`manufactured in America.
`
`About Antares Pharma
`
`Antares Pharma focuses on self-administered parenteral pharmaceutical products. The Company has received
`marketing approval from the U.S. Food and Drug Administration for OTREXUP (methotrexate) injection for the treatment
`of adults with severe active rheumatoid arthritis, children with active polyarticular juvenile idiopathic arthritis and adults
`with severe recalcitrant psoriasis. Antares Pharma is also developing VIBEX QS T for testosterone replacement therapy.
`The Company's technology platforms include VIBEX disposable Medi-Jet, disposable multi-use pen injectors and
`reusable needle-free injectors marketed as Tjet and Zomajet by Teva Pharmaceutical Industries, Ltd (Teva) and Ferring
`Pharmaceuticals (Ferring), respectively. Antares Pharma has a multi-product deal with Teva that includes Tev-Tropin
`[somatropin (rDNA origin) for injection] human growth hormone (hGH), VIBEX epinephrine and several other products.
`Antares Pharma’s partnership with Ferring includes Zomacton hGH (somatropin) injection. In the U.S. Antares has
`received FDA approval for Gelnique 3% (oxybutynin) gel, a treatment for overactive bladder that is marketed by Actavis.
`Elestrin (estradiol gel) is FDA approved for the treatment of moderate-to-severe vasomotor symptoms associated with
`menopause, and is marketed in the U.S. by Meda Pharma. Antares Pharma has two facilities in the U.S. The Parenteral
`Products Group located in Minneapolis, Minnesota directs the manufacturing and marketing of the Company’s reusable
`needle-free injection devices and related disposables, and develops its disposable pressure-assisted Medi-Jet and pen
`injector systems. The Company’s corporate office and Product Development and Commercial Groups are located in
`Ewing, New Jersey.
`
`Safe Harbor Statement
`
`This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private
`Securities Litigation Reform Act of 1995. These statements are indicated by the words “may,” “will,” “plans,” “intends,”
`“believes,” “expects,” “anticipates,” “potential,” “could,” “would,” “should,” and similar expressions. Such forward-looking
`statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual
`results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties
`include, among others, changes in revenue growth and difficulties or delays in the initiation, progress, or completion of
`product development. Additional information concerning these and other factors that may cause actual results to differ
`materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the
`Company's Annual Report on Form 10-K for the year ended December 31, 2013, and in the Company's other periodic
`reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue
`reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on
`information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise
`or update these forward-looking statements to reflect events or circumstances after the date of this press release, except
`as required by law.
`
`Contacts
`Antares Pharma, Inc.
`Jack Howarth
`Vice President, Corporate Affairs
`609-359-3016
`jhowarth@antarespharma.com
`
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