FDA Approves Darzalex (daratumumab) Split-Dosing Regimen

Horsham, PA, February 12, 2019 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has approved a split-dosing regimen for Darzalex® (daratumumab), providing healthcare professionals and patients with multiple myeloma an option to split the first infusion over two consecutive days.[1] The U.S. FDA approval is based on data from the Phase 1b EQUULEUS (MMY1001) clinical study, which demonstrated Darzalex pharmacokinetic (PK) concentrations were comparable at the end of weekly dosing, regardless of whether the first dose was administered as a split infusion or as a single infusion.1

“The first infusion of Darzalex is an important first step in a patient’s course of therapy, and this approval provides added flexibility for how patients may receive initial treatment,” said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Janssen Research & Development, LLC. “We are committed to exploring options that may improve the overall treatment experience for patients.”

The U.S. FDA approval of a split-dosing regimen for Darzalex is based on data from the global, multi-arm, Phase 1b EQUULEUS (MMY1001) study in multiple myeloma, which evaluated Darzalex in combination with various treatment regimens.1 Splitting the first dose of Darzalex over two consecutive days effectively reduced the duration of the first infusion and resulted in a similar rate and pattern of infusion reactions.1 Data from the study demonstrated that Darzalex concentrations were comparable at the end of weekly dosing regardless of whether the first 16 mg/kg dose was administered as a split infusion or single first infusion.1

The safety profile of DARZALEX was comparable when administered initially as a split or single dose, and no new safety events were observed with a split first dose.1

This approval follows approvals in Canada and the European Union in December 2018 for the Darzalex initial infusion split-dosing regimen.

About Darzalex (daratumumab) Injection for Intravenous Infusion

Darzalex is the first and only CD38-directed antibody to receive regulatory approval to treat multiple myeloma.[2] In the U.S., Darzalex (daratumumab) first received FDA approval in November 2015 as a monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent.[3] Darzalex received additional approvals in November 2016 in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.[4] In June 2017, Darzalex received approval in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a PI.[5] Most recently, in May 2018, Darzalex received approval in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, making it the first monoclonal antibody approved for newly diagnosed patients with this disease.[6]

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered into a global license and development agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize Darzalex.[7] For the full U.S. Prescribing Information, please visit www.DARZALEX.com.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.[8],[9] Refractory cancer occurs when a patient’s disease is resistant to treatment or in the case of multiple myeloma, when patients progress within 60 days of their last therapy.[10],[11] Relapsed cancer means the disease has returned after a period of initial, partial or complete remission.[12] In 2019, it is estimated that 32,110 people will be diagnosed, and 12,960 will die from the disease, in the United States.[13] While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood counts, fatigue, high calcium levels, kidney problems or infections.[14]

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science.

We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

# # #

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding the benefits of Darzalex® (daratumumab) for the treatment of patients with multiple myeloma. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; [product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2017, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies of Johnson & Johnson nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

    1. [1] Janssen Research & Development, LLC. A Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Treatments for the Treatment of Patients With Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT01998971 Identifier: NCT01998971

 

    1. [2] Darzalex Prescribing Information, June 2018.

 

    1. [3] Janssen Biotech, Inc. “Darzalex® (daratumumab) Approved by U.S. FDA: First Human Anti-CD38 Monoclonal Antibody Available for the Treatment of Multiple Myeloma.” Issued November 16, 2015.

 

    1. [4] Janssen Biotech, Inc. “Darzalex® (daratumumab) Approved by U.S. FDA in Combination with Two Standard of Care Regimens for the Treatment of Patients with Multiple Myeloma Who Have Received At Least One Prior Therapy.” Issued November 21, 2016.

 

    1. [5] Janssen Biotech, Inc. “Darzalex® (daratumumab) Approved by the U.S. FDA in Combination with Pomalidomide and Dexamethasone for Patients with Multiple Myeloma Who Have Received At Least Two Prior Therapies.” Issued June 16, 2017.

 

    1. [6] Janssen Pharmaceutical Companies of Johnson & Johnson. “Janssen Announces Darzalex® (daratumumab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible.” Issued May 7, 2018.

 

    1. [7] Janssen Biotech, Inc. “Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab.” Issued August 30, 2012.

 

    1. [8] Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.

 

    1. [9] American Cancer Society. “What Is Multiple Myeloma?” Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed August 2018. Accessed February 2019.

 

    1. [10] National Cancer Institute. “NCI Dictionary of Cancer Terms: Refractory.” Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245. Accessed February 2019.

 

    1. [11] Richardson, et al. “The Treatment of Relapsed and Refractory Multiple Myeloma.” ASH Education Book. January 1, 2007 vol. 2007 no. 1 317-323.

 

    1. [12] National Cancer Institute. “NCI Dictionary of Cancer Terms: Relapsed.” Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866. Accessed February 2019.

 

    1. [13] American Cancer Society. “Key Statistics for Multiple Myeloma.” Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed February 2019.

 

    1. [14] American Cancer Society. “Diagnosing Multiple Myeloma From Test Results.” Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed February 2019.

 

Source: Janssen Pharmaceutical Companies of Johnson & Johnson

Posted: February 2019

Related Articles:

Darzalex (daratumumab) FDA Approval History

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FDA Approves Jeuveau (prabotulinumtoxinA-xvfs) for Temporary Improvement in the Appearance of Frown Lines

FDA Approves Jeuveau (prabotulinumtoxinA-xvfs) for Temporary Improvement in the Appearance of Frown Lines

NEWPORT BEACH, Calif., Feb. 01, 2019 (GLOBE NEWSWIRE) — Evolus, Inc. (NASDAQ: EOLS) today announced that the U.S. Food and Drug Administration (“FDA”) has approved its lead product, Jeuveau, for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adults.

David Moatazedi, President and Chief Executive Officer of Evolus, stated, “Evolus is the first company in nearly a decade to enter the fast-growing U.S. aesthetic neurotoxin market. What makes Evolus unique is our focus on delivering performance beauty products with a customer-centric approach. We are pleased to introduce Jeuveau™, the first FDA approved neurotoxin dedicated to aesthetics and manufactured in a state-of-the-art facility using Hi-Pure™ technology.”

Ava Shamban, MD, Board Certified Dermatologist and clinical investigator, commented, “The outcomes I’ve seen for my clinical trial patients firsthand, combined with the comprehensive clinical data set for Jeuveau provide a compelling new treatment option for physicians and their aesthetic patients. The TRANSPARENCY program involved the study of over 2,100 patients globally, which included two U.S. pivotal Phase III trials and a European & Canadian Phase III head-to-head trial versus Botox®, in which all the primary and secondary endpoints were met. Importantly, there were no serious drug related adverse events reported. The comprehensive data set generated by Evolus through the TRANSPARENCY clinical program will give my peers the utmost level of confidence in providing Jeuveau to their patients. I look forward to incorporating Jeuveau into my aesthetic product offering.”

Mr. Moatazedi added, “We are focusing our efforts on ensuring a successful launch of Jeuveau and have initiated the recruitment of a high-quality, specialized U.S. sales force. The launch of Jeuveau™ will be powered by our technology platform designed to eliminate the friction points that exist for customers today. Prior to our U.S. launch, we expect publication of our U.S. Phase III results and to submit for publication our European and Canadian head-to-head Phase III study versus Botox®. I would like to thank all the Evolus employees, clinical investigators, patients and our partner Daewoong for their diligent efforts in bringing a new option to the market.”

Jeuveau is expected to be available throughout the United States at physician offices starting in Spring 2019. Physicians and consumers are encouraged to visit www.evolus.com and sign up for updates on product availability.

About Jeuveau

Jeuveau (prabotulinumtoxinA-xvfs) is a proprietary 900 kDa purified botulinum toxin type A formulation indicated for the temporary improvement in the appearance of moderate to severe glabellar lines in adults. Jeuveau is produced under strict quality and safety standards in a state-of-the art facility, specifically built to manufacture Jeuveau. The safety and efficacy of Jeuveau has been evaluated in clinical studies with over 2,100 patients enrolled.

FDA approval of Jeuveau was supported by clinical data from two U.S. Phase III randomized, multi-center, double-blind, placebo-controlled clinical trials both of which met the primary endpoint and demonstrated efficacy compared with placebo in the reduction of the severity of glabellar lines, defined as a 2-point composite improvement agreed upon by physician and patient, at Day 30.  67.5% of subjects in study one (EV-001) and 70.4% of subjects in study two (EV-002) met the primary endpoint, compared to 1.2% and 1.3% of patients in each placebo arm respectively.

IMPORTANT SAFETY INFORMATION FOR JEUVEAU (prabotulinumtoxinA-xvfs)

Jeuveau may cause serious side effects that can be life threatening. Get medical help right away if you have any of these problems any time (hours to weeks) after injection of Jeuveau:

Problems swallowing, speaking, or breathing, due to weakening of associated muscles, can be severe and result in loss of life. You are at the highest risk if these problems are pre-existing before injection. Swallowing problems may last for several months.

Spread of toxin effects. The effect of botulinum toxin may affect areas away from the injection site and cause serious symptoms including: loss of strength and all-over muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing.

Do not use Jeuveau if you: are allergic to any of the ingredients in Jeuveau (see Medication Guide for ingredients); had an allergic reaction to any other botulinum toxin product such as rimabotulinumtoxinB (MYOBLOC®), onabotulinumtoxinA (BOTOX®/BOTOX® Cosmetic), abobotulinumtoxinA (DYSPORT®), or incobotulinumtoxinA (XEOMIN®); have a skin infection at the planned injection site; or are a child.

Jeuveau dosing units are not the same as, or comparable to, any other botulinum.

Tell your healthcare provider about all your muscle or nerve conditions, such as ALS or Lou Gehrig’s disease, Myasthenia gravis, or Lambert-Eaton syndrome, as you may be at increased risk of serious side effects including difficulty swallowing and difficulty breathing from typical doses of Jeuveau.

Tell your healthcare provider about all your medical conditions, including: any side effects from botulinum toxin products, including dry eye; breathing, swallowing, bleeding, or heart problems; plans to have surgery; weakness of forehead muscles; drooping eyelids; had surgery on your face; are pregnant or breastfeeding or plan to become pregnant or breastfeed (it is not known if Jeuveau can harm your unborn baby or passes into breast milk).

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using Jeuveau with certain other medicines may cause serious side effects. Do not start any new medicines until you have told your healthcare provider that you have received Jeuveau in the past.

Especially tell your healthcare provider if you: have received any other botulinum toxin product in the past and the last 4 months. and exactly which product you received (such as Botox, Botox Cosmetic, Myobloc, Dysport, or Xeomin).

Jeuveau may cause loss of strength or general muscle weakness, vision problems, or dizziness within hours to weeks of treatment with Jeuveau. If this happens, do not drive a car, operate machinery, or do other dangerous activities.

Jeuveau can cause other serious side effects including: allergic reactions (such as itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint), heart problems (such as irregular heartbeat and heart attack), and eye problems (including dry eye, reduced blinking, and corneal problems). Tell your healthcare provider or get medical emergency help right away if you experience a serious side effect.

The most common side effects include: headache; eyelid drooping, upper respiratory tract infection, and increased white blood cell count in your blood.

APPROVED USE

Jeuveau is a prescription medicine that is injected into muscles and used in adults for a short period of time (temporary) to improve the look of moderate to severe frown lines between the eyebrows (glabellar lines).

The risk information provided here is not complete. For more information about Jeuveau, the full Prescribing Information including BOXED WARNING, and Medication Guide, visit www.evolus.com or talk to your healthcare provider.

To report side effects associated with use of Jeuveau, please call 1-877-386-5871. 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.

Manufactured by: Evolus, Inc., 1027 Garden St., Santa Barbara, CA 93101

©2019 Evolus, Inc. All rights reserved. Jeuveau is a trademark of Evolus, Inc. All other trademarks are the property of their respective owners.

About Evolus, Inc.

Evolus is a performance beauty company with a customer-centric approach focused on delivering breakthrough products. In 2019, the U.S. Food and Drug Administration approved Jeuveau (prabotulinumtoxinA-xvfs), the first and only neurotoxin dedicated exclusively to aesthetics and manufactured in a state-of-the-art facility using Hi-Pure™ technology. Jeuveau is powered by Evolus’ unique technology platform and is designed to transform the aesthetic market by eliminating the friction points existing for customers today. Visit us at: www.evolus.com.

Forward-Looking Statements

Statements made in this press release that relate to future plans, events, prospects or performance are forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including statements containing the words “planned,” “expect,” “believes,” “strategy,” “opportunity,” “anticipates,” “outlook,” “designed,” and similar words. While these forward-looking statements are based on the current expectations and beliefs of management, such forward-looking statements are subject to a number of risks, uncertainties, assumptions and other factors that could cause actual results to differ materially from the expectations expressed in this press release, including the risks and uncertainties disclosed in Evolus’ periodic filings with the Securities and Exchange Commission, including factors described in the section entitled ”Risk Factors” in its Annual Report on Form 10-K for the year ended December 31, 2017 and its Quarterly Report on Form 10-Q for the Quarter ended September 30, 2018, as filed with the Securities and Exchange Commission on March 29, 2018 and November 5, 2018, respectively, all of which are available online at www.sec.gov. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by law, Evolus undertakes no obligation to update or revise any forward-looking statements to reflect new information, changed circumstances or unanticipated events.

Jeuveau is a trademark of Evolus, Inc.

Hi-Pure is a trademark of Daewoong Pharmaceutical Co, Ltd.

Botox®, Botox® Cosmetic, Myobloc®, Dysport®, and Xeomin® are registered trademarks of their respective owners.

Source: Evolus

Posted: February 2019

Related Articles:

Jeuveau (prabotulinumtoxinA-xvfs) FDA Approval History

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ENT Drug Approval Process

Drug Testing And Approval Timeline -ENT

Although many of the FDA’s risk-benefit assessments and decisions are straightforward, sometimes the benefits and risks are uncertain and may be difficult to interpret or predict. The agency and the drug maker may reach different conclusions after analyzing the same data, or there may be differences of opinion among members of the FDA’s review team. As a science-led organization, FDA uses the best scientific and technological information available to make decisions through a deliberative process.

Faster Approvals

In some cases, the approval of a new drug is expedited. Accelerated Approval can be applied to promising therapies that treat a serious or life-threatening condition and provide therapeutic benefit over available therapies. This approach allows for the approval of a drug that demonstrates an effect on a “surrogate endpoint” that is reasonably likely to predict clinical benefit, or on a clinical endpoint that occurs earlier but may not be as robust as the standard endpoint used for approval. This approval pathway is especially useful when the drug is meant to treat a disease whose course is long, and an extended period of time is needed to measure its effect. After the drug enters the market, the drug maker is required to conduct post-marketing clinical trials to verify and describe the drug’s benefit. If further trials fail to verify the predicted clinical benefit, FDA may withdraw approval.

Since the Accelerated Approval pathway was established in 1992, many drugs that treat life-threatening diseases have successfully been brought to market this way and have made a significant impact on disease course. For example, many antiretroviral drugs used to treat HIV/AIDS entered the market via accelerated approval, and subsequently altered the treatment paradigm. A number of targeted cancer-fighting drugs also have come onto the market through this pathway.

More information on Accelerated Approval is here.

Inventing New Medications

American consumers benefit from having access to the safest and most advanced pharmaceutical system in the world. The main consumer watchdog in this system is FDA’s Center for Drug Evaluation and Research (CDER).

The center’s best-known job is to evaluate new drugs before they can be sold. CDER’s evaluation not only prevents quackery, but also provides doctors and patients the information they need to use medicines wisely. The center ensures that drugs, both brand-name and generic, work correctly and that their health benefits outweigh their known risks.

Drug companies seeking to sell a drug in the United States must first test it. The company then sends CDER the evidence from these tests to prove the drug is safe and effective for its intended use. A group of physicians, statisticians, chemists, pharmacologists, and other scientists reviews the company’s data and proposed labeling. If this independent and unbiased review establishes that a drug’s health benefits outweigh its known risks, the drug is approved for sale. The center doesn’t actually test drugs itself, although it does conduct limited research in the areas of drug quality, safety, and effectiveness standards.

Before a drug can be tested in people, the drug company or sponsor performs laboratory and animal tests to discover how the drug works and whether it’s likely to be safe and work well in humans. Next, a series of tests in people is begun to determine whether the drug is safe when used to treat a disease and whether it provides a real health benefit.

For more information about the drug development and approval process, see How Drugs Are Developed and Approved.

FDA Approval: What it means

FDA approval of a drug means that data on the drug’s effects have been reviewed by CDER, and the drug is determined to provide benefits that outweigh its known and potential risks for the intended population. The drug approval process takes place within a structured framework that includes:

  • Analysis of the target condition and available treatments—FDA reviewers analyze the condition or illness for which the drug is intended and evaluate the current treatment landscape, which provide the context for weighing the drug’s risks and benefits. For example, a drug intended to treat patients with a life-threatening disease for which no other therapy exists may be considered to have benefits that outweigh the risks even if those risks would be considered unacceptable for a condition that is not life threatening.
  • Assessment of benefits and risks from clinical data—FDA reviewers evaluate clinical benefit and risk information submitted by the drug maker, taking into account any uncertainties that may result from imperfect or incomplete data. Generally, the agency expects that the drug maker will submit results from two well-designed clinical trials, to be sure that the findings from the first trial are not the result of chance or bias. In certain cases, especially if the disease is rare and multiple trials may not be feasible, convincing evidence from one clinical trial may be enough. Evidence that the drug will benefit the target population should outweigh any risks and uncertainties.
  • Strategies for managing risks—All drugs have risks. Risk management strategies include an FDA-approved drug label, which clearly describes the drug’s benefits and risks, and how the risks can be detected and managed. Sometimes, more effort is needed to manage risks. In these cases, a drug maker may need to implement a Risk Management and Mitigation Strategy (REMS).

Ear Nose and Throat Medications

With the coming of winter and people far and wide spending time cozy and together it is Flu and Cold season!

Our friends at Miami Rhinoplasty Specialist provide a list of over the counter medications for anyone’s holiday season.

For body aches, doctors suggest you give your child over-the-counter (OTC) acetaminophen, ibuprofen, or naproxen sodium. Don’t give aspirin to anyone under 19 years old. It’s linked with Reye’s syndrome, a sometimes fatal illness that affects children and teens. To avoid stomach upset, take ibuprofen with food.

Kids

Don’t give OTC cough medicines to kids under 4. They don’t work. Homemade cough remedies with honey do help. After your child is 1 year old, you can use ½ to 1 teaspoon of honey as needed.

Home Remedies

Lozenges with licorice and slippery elm: They ease sore throats and coughs from all that gunk running down the back of your throat. (Doctors call this postnasal drip.)

  • Ginger tea: It helps with nausea.