FDA Approves New Formulation of MINOCIN® (minocycline) for Injection

20 Apr 2015

The Medicines Company (NASDAQ:MDCO) today announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for a new formulation of MINOCIN® (minocycline) for Injection.

The FDA has also granted Qualified Infectious Disease Product (QIDP) designation for the new formulation of MINOCIN for Injection under the Generating Antibiotic Incentives Now Act (GAIN Act). The designation, the third granted to a product in the Company’s infectious disease portfolio, would qualify MINOCIN for Injection for priority review and five years of marketing exclusivity upon an approval of the additional potential indications.

Multi-drug resistant Acinetobacter is considered to be a serious antimicrobial resistance threat by the US Centers for Disease Control and Prevention (CDC). CDC estimates the number of deaths with onset in hospitalized patients due to multi-drug resistant Acinetobacter to be higher than those attributed to multi-drug resistant Pseudomonas aeruginosa. According to published estimates (Spellberg and Rex, Nature Reviews/Drug Discovery, 2013), there may be up to 80,000 infections due to Acinetobacter species annually in the US, and one million deaths worldwide.

MINOCIN for Injection is a tetracycline derivative approved in the U.S. The approved indications for MINOCIN for Injection includes the treatment of infections due to susceptible strains of several important designated gram-positive and gram-negative pathogens, including infections due to Acinetobacter species, which typically occur in hospitalized patients.

“We believe the new formulation of MINOCIN for Injection will offer clinicians an improved IV formulation that may allow for easier administration by using a lower fluid volume in patients with serious infections, including those caused by Acinetobacter spp.,” said Michael Dudley, PharmD., Senior Vice President and Head of Global Health Science, Infectious Disease Global Innovation Group, The Medicines Company. “We are also pleased that FDA has recognized the potential value MINOCIN for Injection can bring to patients with difficult-to-treat infections due to serious pathogens by granting QIDP designation.”

“Clinicians, regulators, and public health authorities have increasingly recognized the threat of multi-drug resistant bacteria to our healthcare system,” said Dr. Debra Goff, PharmD., FCCP Infectious Disease Specialist, The Ohio State University Wexner Medical Center. “MINOCIN for injection is an example of stewardship efforts to identify drugs to meet the challenge of infections in the hospital. Patients and clinicians have very limited choices, and thus having FDA-approved drugs for treatment of infections due to Acinetobacter spp. will be important for their treatment.”

QIDP Designation

The FDA granted QIDP designation for the following potential indications involving gram-negative pathogens:

  • Treatment of hospital acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP).
  • Treatment of persistent pulmonary infections in patients with cystic fibrosis caused by Burkholderia cepacia complex or Stenotrophomonas maltophilia.
  • Treatment of pulmonary exacerbations in patients with cystic fibrosis caused by Burkholderia cepacia complex or Stenotrophomonas maltophilia.
  • Treatment of pulmonary infections including pneumonia or lung abscess in patients with chronic granulomatous disease caused by Burkholderia cepacia complex.

MINOCIN for Injection is one of the products in the company’s growing anti-infective portfolio including a development portfolio focused on providing clinicians and patients innovative products for the treatment of resistant gram-negative pathogens.

The FDA has previously granted QIDP designation to ORBACTIV™ (oritavancin) which was approved by the agency in August 2014, and CARBAVANCE™ (meropenem/RPX 7009), an investigational agent being developed to treat serious gram-negative infections, such as cUTIs, including those infections caused by bacteria resistant to currently available carbapenems.

About MINOCIN® (minocycline) for Injection

Indication

MINOCIN® (minocycline) for Injection is indicated for the treatment of infections due to susceptible strains of designated microorganisms, including Acinetobacter species bacteria. For additional full list of indications and designated susceptible pathogens, please see the full prescribing information available at www.minociniv.com.

IMPORTANT SAFETY INFORMATION

Contraindications

MINOCIN® (minocycline) for Injection is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or to any of the components of the product formulation.

Warnings

Tooth Development

MINOCIN, like other tetracycline-class antibacterials, can cause fetal harm when administered to a pregnant woman. If any tetracycline is used during pregnancy, or if the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the fetus. The use of drugs of the tetracycline class during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown).

This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Tetracycline drugs, therefore, should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated.

Skeletal Development

All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has been noted in animals treated early in pregnancy.

Dermatologic Reaction

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) including fatal cases have been reported with minocycline use. If this syndrome is recognized, the drug should be discontinued immediately.

Anti-anabolic Action

The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline may lead to azotemia, hyperphosphatemia, and acidosis. Under such conditions, monitoring of creatinine and BUN is recommended, and the total daily dosage should not exceed 200 mg in 24 hours. If renal impairment exists, even usual oral or parenteral doses may lead to systemic accumulation of the drug and possible liver toxicity.

Photosensitivity

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. This has been reported with minocycline.

Central Nervous System Effects

Central nervous system side effects including light-headedness, dizziness or vertigo have been reported. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. These symptoms may disappear during therapy and usually disappear rapidly when the drug is discontinued.

Clostridium difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including MINOCIN®, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued.

Intracranial Hypertension

Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including Minocin. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and Minocin should be avoided because isotretinoin is also known to cause pseudotumor cerebri.

Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize.

PRECAUTIONS

As with other antibacterial preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibacterial should be discontinued and appropriate therapy instituted.

Hepatotoxicity has been reported with minocycline; therefore, minocycline should be used with caution in patients with hepatic dysfunction and in conjunction with other hepatotoxic drugs.

Incision and drainage or other surgical procedures should be performed in conjunction with antibiotic antibacterial therapy when indicated.

MINOCIN (minocycline) Injection contains magnesium sulphate heptahydrate. Because magnesium is excreted primarily by the kidney, serum levels of magnesium should be monitored in patients with renal impairment.

Because MINOCIN (minocycline) Injection contains magnesium, close monitoring is recommended in patients with heart block or myocardial damage.

Prescribing MINOCIN (minocycline) Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions

For a complete list of adverse reactions that have been observed in patients receiving tetracyclines, consult the full prescribing information for MINOCIN® (minocycline) for injection.

About ORBACTIV® (oritavancin)

ORBACTIV® (oritavancin) for injection received FDA approval in the U.S. in August 2014. ORBACTIV is the first and only FDA-approved single-dose IV antibiotic for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused or suspected to be caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin–resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis (vancomycin-susceptible isolates only).

IMPORTANT SAFETY INFORMATION

Contraindications

Use of intravenous unfractionated heparin sodium is contraindicated for 48 hours after ORBACTIV administration because the activated partial thromboplastin time (aPTT) test results are expected to remain falsely elevated for approximately 48 hours after ORBACTIV administration.

ORBACTIV is contraindicated in patients with known hypersensitivity to ORBACTIV.

Warnings and Precautions

Concomitant warfarin use: Co-administration of ORBACTIVand warfarin may result in higher exposure of warfarin, which may increase the risk of bleeding. Use ORBACTIV in patients on chronic warfarin therapy only when the benefits can be expected to outweigh the risk of bleeding.

Coagulation test interference: ORBACTIV has been shown to artificially prolong aPTT for up to 48 hours, and may prolong PT and INR for up to 24 hours.

Hypersensitivity reactions have been reported with the use of antibacterial agents including ORBACTIV. Discontinue infusion if signs of acute hypersensitivity occur. Monitor closely patients with known hypersensitivity to glycopeptides.

Infusion-related reactions have been reported. Slow the rate or interrupt infusion if infusion reaction develops.

Clostridium difficile-associated colitis: Evaluate patients if diarrhea occurs.

Osteomyelitis: Institute appropriate alternate antibacterial therapy in patients with confirmed or suspected osteomyelitis.

Prescribing ORBACTIV in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions

The most common adverse reactions (? 3%) in patients treated with ORBACTIV were headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea.

Please see www.orbactiv.com for the full US prescribing information.

About The Medicines Company Infectious Disease Portfolio

The Medicines Company is well positioned to address the complex problems associated with multi-drug resistant infections. The research projects, development programs, and marketed products span the spectrum of infections caused by certain Gram-positive bacteria, including Methicillin-Resistant Staphylococcus Aureus (MRSA), and Gram-negative infections including Acinetobacter spp, carbapenem-resistant Enterobacteriaceae and other multi-drug-resistant pathogens identified by US Centers of Disease Control as urgent or serious threats. The product pipeline includes CARBAVANCE™ (meropenem/RPX7009) and pre-clinical developmental program of novel investigational agents. ORBACTIV and MINOCIN for injection are two antibiotics approved for use in the US. The product portfolio has the potential to offer clinicians and patients a suite of innovative new antibiotic approaches to tackle many of the most vexing problems in infectious disease today.

About The Medicines Company

The Medicines Company's purpose is to save lives, alleviate suffering and contribute to the economics of healthcare by focusing on 3000 leading acute/intensive care hospitals worldwide. Its vision is to be a leading provider of solutions in three areas: serious infectious disease care, acute cardiovascular care and surgery and perioperative care. The company operates in the Americas, Europe and the Middle East, and Asia Pacific regions with global centers today in Parsippany, NJ, USA and Zurich, Switzerland.

Forward-Looking Statements

Statements contained in this press release about The Medicines Company that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "believes," "anticipates," "expects," “hopes” and “potential” and similar expressions, are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company's actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include whether the Company's products will advance in the clinical trials process on a timely basis or at all, whether the Company will make regulatory submissions for product candidates on a timely basis, whether its regulatory submissions will receive approvals from regulatory agencies on a timely basis or at all, whether physicians, patients and other key decision makers will accept clinical trial results and such other factors as are set forth in the risk factors detailed from time to time in the Company's periodic reports and registration statements filed with the Securities and Exchange Commission including, without limitation, the risk factors detailed in the Company's Annual Report on Form 10-K filed with the SEC on March 2, 2015, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.


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