FDA Approves Expanded Monotherapy Label for Merck’s Keytruda (pembrolizumab) for First-Line Treatment of NSCLC

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded label for Keytruda, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. The approval is based on results from the Phase 3 KEYNOTE-042 trial, in which overall survival (OS) was sequentially tested as part of a pre-specified analysis plan. In the trial, Keytruda monotherapy demonstrated a statistically significant improvement in OS compared with chemotherapy alone in patients whose tumors expressed PD-L1 with a TPS ≥50%, with a TPS ≥20%, and then in the entire study population (TPS ≥1%).

“This expanded first-line indication now makes Keytruda monotherapy an option for more patients with non-small cell lung cancer, including those for whom combination therapy may not be appropriate,” said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.

“The KEYNOTE-042 trial demonstrated a survival benefit with Keytruda monotherapy across histologies in certain patients with stage III or metastatic non-small cell lung cancer whose tumors expressed PD-L1 in at least 1% of tumor cells,” said Dr. Gilberto Lopes, associate director for global oncology at the Sylvester Comprehensive Cancer Center at the University of Miami. “As a practicing oncologist, having additional options available for patients is important in the rapidly evolving treatment landscape for lung cancer, which remains the leading cause of cancer death in the United States.”

Keytruda was the first anti-PD-1 therapy in metastatic NSCLC approved in the first-line setting as combination therapy or monotherapy.

About KEYNOTE-042

The approval was based on data from the KEYNOTE-042 trial, a randomized, multi-center, open-label, active-controlled trial in patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors expressed PD-L1 (TPS ≥1%) and who had not received prior systemic treatment for metastatic NSCLC. Patients with EGFR or ALK genomic tumor aberrations; autoimmune disease that required systemic therapy within two years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of radiation in the thoracic region within 26 weeks prior to initiation of study treatment were ineligible.

The study enrolled 1,274 patients who were randomized (1:1) to receive Keytruda 200 mg intravenously every three weeks (n=637) or investigator’s choice of either of the following chemotherapy regimens (n=637):

  • Pemetrexed 500 mg/m2 every three weeks and carboplatin AUC 5 to 6 mg/mL/min every three weeks on Day 1 for a maximum of six cycles followed by optional pemetrexed 500 mg/m2 every three weeks for patients with nonsquamous histologies; or
  • Paclitaxel 200 mg/m2 every three weeks and carboplatin AUC 5 to 6 mg/mL/min every three weeks on Day 1 for a maximum of six cycles followed by optional pemetrexed 500 mg/m2 every three weeks for patients with nonsquamous histologies

Treatment with Keytruda continued until RECIST v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ)-defined progression of disease, unacceptable toxicity, or a maximum of 24 months. The main efficacy outcome measure was OS in the subgroup of patients with TPS ≥50% NSCLC, the subgroup of patients with TPS ≥20% NSCLC, and the overall population with TPS ≥1% NSCLC. Additional efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) in the subgroup of patients with TPS ≥50% NSCLC, the subgroup of patients with TPS ≥20% NSCLC, and the overall population with TPS ≥1% NSCLC as assessed by a blinded independent central radiologists’ (BICR) review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

Efficacy Results from KEYNOTE-042

    TPS ≥1%   TPS ≥50%
Endpoint   KEYTRUDA

200 mg every 3 weeks

n=637

  Chemotherapy

n=637

  KEYTRUDA

200 mg every 3 weeks

n=299

  Chemotherapy

n=300

OS
Number of events (%)   371 (58%)   438 (69%)   157 (53%)   199 (66%)
Median in months (95% CI)   16.7

(13.9-19.7)

  12.1

(11.3-13.3)

  20.0

(15.4-24.9)

  12.2

(10.4-14.2)

Hazard ratio (HR)* (95% CI)   0.81 (0.71-0.93)   0.69 (0.56-0.85)
p-Value   0.0036   0.0006
PFS
Number of events (%)   507 (80%)   506 (79%)   221 (74%)   233 (78%)
Median in months (95% CI)   5.4

(4.3-6.2)

  6.5

(6.3-7.0)

  7.1

(5.9-9.0)

  6.4

(6.1-6.9)

HR*,‡ (95% CI)   1.07 (0.94-1.21)   0.81 (0.67-0.99)
p-Value     NS§
Objective Response Rate
ORR (95% CI)   27%

(24-31)

  27%

(23-30)

  39%

(33.9-45.3)

  32%

(26.8-37.6)

Complete response rate   0.5%   0.5%   0.7%   0.3%
Partial response rate   27%   26%   39%   32%
Duration of Response
% with duration ≥ 12 months   47%   16%   42%   17%
% with duration ≥ 18 months   26%   6%   25%   5%

 * Based on the stratified Cox proportional hazard model

† Based on a stratified log-rank test; compared to a p-Value boundary of 0.0291
‡ Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints
§ Not significant compared to a p-Value boundary of 0.0291
¶ Based on observed duration of response

The results of all efficacy outcome measures in the subgroup of patients with PD-L1 TPS ≥20% NSCLC were intermediate between the results of those with PD-L1 TPS ≥1% and those with PD-L1 TPS ≥50%. In a pre-specified exploratory subgroup analysis for patients with TPS 1-49% NSCLC, the median OS was 13.4 months (95% CI, 10.7-18.2) for the Keytruda group and 12.1 months (95% CI, 11.0-14.0) in the chemotherapy group, with an HR of 0.92 (95% CI, 0.77-1.11).

In KEYNOTE-042, the safety of Keytruda was investigated in patients with PD-L1 expressing, previously untreated stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC. Keytruda was discontinued for adverse reactions in 19% of 636 patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda were pneumonitis (3.0%), death due to unknown cause (1.6%), and pneumonia (1.4%). Adverse reactions leading to interruption of Keytruda occurred in 33% of patients; the most common adverse reactions or laboratory abnormalities leading to interruption of Keytruda (≥2%) were pneumonitis (3.1%), pneumonia (3.0%), hypothyroidism (2.2%), and increased ALT (2.0%). The most frequent (≥2%) serious adverse reactions were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) with Keytruda was fatigue (25%).

About Keytruda ® (pembrolizumab) Injection, 100mg

Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 950 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About the Merck Access Program for Keytruda

At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help ensure that appropriate patients who are prescribed Keytruda have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving Keytruda, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. Merck also offers free product through our patient assistance program to eligible patients, primarily the uninsured, who, without our assistance, could not afford their medicine. More information is available by calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com.

About Merck’s Patient Support Program for Keytruda

Merck is committed to helping provide patients and their caregivers support throughout their treatment with Keytruda. The KEY+YOU Patient Support Program provides a range of resources and services. For further information and to sign up, patients and physicians may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com.

About Merck

For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2018 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov ).

Please see Prescribing Information for Keytruda at  http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf  and Medication Guide for Keytruda at  http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .

Source: Merck

Posted: April 2019

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FDA Approves Balversa (erdafitinib) for the Treatment of Metastatic Bladder Cancer

FDA Approves Balversa (erdafitinib) for the Treatment of Metastatic Bladder Cancer

April 12, 2019 — The U.S. Food and Drug Administration today granted accelerated approval to Balversa (erdafitinib), a treatment for adult patients with locally advanced or metastatic bladder cancer that has a type of susceptible genetic alteration known as FGFR3 or FGFR2, and that has progressed during or following prior platinum-containing chemotherapy. Patients should be selected for therapy with Balversa using an FDA-approved companion diagnostic device.

“We’re in an era of more personalized or precision medicine, and the ability to target cancer treatment to a patient’s specific genetic mutation or biomarker is becoming the standard, with advances being made in new disease types. Today’s approval represents the first personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “FGFRs regulate important biological processes including cell growth and division during development and tissue repair. This drug works by targeting genetic alterations in FGFRs.”

The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Bladder cancers are associated with genetic mutations that are present in the patient’s bladder or entire urothelium (the lining of the lower urinary tract). Bladder cancer is the sixth most common cancer in the United States. Fibroblast growth factor (FGFR) alterations are present in approximately one in five patients with recurrent and refractory bladder cancer.

The efficacy of Balversa was studied in a clinical trial that included 87 patients with locally advanced or metastatic bladder cancer, with FGFR3 or FGFR2 genetic alterations, that had progressed following treatment with chemotherapy. The overall response rate in these patients was 32.2%, with 2.3% having a complete response and almost 30% having a partial response. The response lasted for an average of approximately five-and-a-half months. About a quarter of patients in the study were previously treated with anti PD-L1/PD-1 therapy, which is a standard treatment for patients with locally advanced or metastatic bladder cancer. Responses to Balversa were seen in patients who had previously not responded to anti PD-L1/PD-1 therapy.

Common side effects reported by patients taking Balversa were increased phosphate level, mouth sores, feeling tired, change in kidney function, diarrhea, dry mouth, nails separating from the bed or poor formation of the nail, change in liver function, low salt (sodium) levels, decreased appetite, change in sense of taste, low red blood cells (anemia), dry skin, dry eyes and hair loss. Other side effects include redness, swelling, peeling or tenderness on the hands or feet (hand foot syndrome), constipation, stomach pain, nausea and muscle pain.

Balversa may cause serious eye problems, including inflamed eyes, inflamed cornea (front part of the eye) and disorders of the retina, an internal part of the eye. Patients are advised to have eye examinations intermittently and to tell their health care professional right away if they develop blurred vision, loss of vision or other visual changes. Health care professionals are advised to check patients’ blood phosphate level between 14 and 21 days after starting treatment and monthly, and to increase the dose Balversa in patients whose serum phosphate is below the target level.

Health care professionals are advised to tell male patients with female partners of reproductive potential to use effective contraception during treatment with Balversa and for one month after the last dose. Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with Balversa. Women who are pregnant or breastfeeding should not take Balversa because it may cause harm to a developing fetus or newborn baby. Balversa must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

Balversa received an Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need using clinical trial data that is thought to predict a clinical benefit to patients. Further clinical trials are required to confirm Balversa’s clinical benefit and the sponsor is conducting or plans to conduct these studies. Balversa was also granted Breakthrough Therapy designation.

The FDA granted the approval of Balversa to Janssen Pharmaceutical.

The FDA also approved the therascreen FGFR RGQ RT-PCR Kit, developed by QIAGEN Manchester, Ltd., for use as a companion diagnostic with Balversa for this therapeutic indication.

Source: FDA

Posted: April 2019

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FDA Approves Ibrance (palbociclib) for the Treatment of Men with HR+, HER2- Metastatic Breast Cancer

April 4, 2019 — Pfizer (NYSE:PFE) today announced that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to expand the indications for Ibrance (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. The approval is based on data from electronic health records and postmarketing reports of the real-world use of Ibrance in male patients sourced from three databases: IQVIA Insurance database, Flatiron Health Breast Cancer database and the Pfizer global safety database.

“With this approval, we are now able to offer Ibrance to the underserved male breast cancer community and provide more patients with HR+, HER2- metastatic breast cancer the opportunity to access an innovative medicine,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “We appreciate that our partnership with the FDA has allowed us to take a significant step forward in the use of real-world data to bring medicines to patients who are most in need.”

Ibrance is now approved for adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy. With today’s approval, Ibrance is the first and only CDK 4/6 inhibitor indicated in combination with an aromatase inhibitor for the first-line treatment of men with HR+, HER2- metastatic breast cancer in the U.S.

“Men with breast cancer have limited treatment options, making access to medicines such as Ibrance critically important,” said Bret Miller, founder of the Male Breast Cancer Coalition. “We applaud the use of real-world data, a new approach to drug review, to make Ibrance available to certain men with metastatic breast cancer and help address an unmet need for these patients.”

Real-world data is playing an increasingly important role in expanding the use of already approved innovative medicines.1 Due to the rarity of breast cancer in males, fewer clinical trials are conducted that include men resulting in fewer approved treatment options. In the U.S. in 2019, it is estimated that there will be 2,670 new cases of invasive breast cancer and about 500 deaths from metastatic breast cancer in males.2 The 21st Century Cures Act, enacted in 2016, was created to help accelerate medical product development, allowing new innovations and advances to become available to patients who need them faster and more efficiently.3 This law places additional focus on the use of real-world data to support regulatory decision-making.4

Detailed analysis of the use of Ibrance in men with HR+, HER2- advanced or metastatic breast cancer will be presented at an upcoming medical meeting. Based on limited data from postmarketing reports and electronic health records, the safety profile for men treated with Ibrance is consistent with the safety profile in women treated with Ibrance.5

About Ibrance (palbociclib) 125 mg capsules

Ibrance is an oral inhibitor of CDKs 4 and 6,6 which are key regulators of the cell cycle that trigger cellular progression.7,8 In the U.S., Ibrance is indicated for the treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

Ibrance currently is approved in more than 90 countries and has been prescribed to more than 200,000 patients globally.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference on the lives of patients. Today, Pfizer Oncology has an industry-leading portfolio of 18 approved innovative cancer medicines and biosimilars across more than 20 indications, including breast, prostate, kidney, lung and hematology. Pfizer Oncology is striving to change the trajectory of cancer.

Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube, and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is as of April 4, 2019. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about the expansion of the indication for Ibrance (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer and Pfizer Oncology, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of Ibrance; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications may be filed in any other jurisdictions for Ibrance, for any additional indications for Ibrance or for any other oncology products; whether and when any such applications may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy, and, if approved, whether Ibrance or any such other oncology products will be commercially successful; decisions by regulatory authorities impacting labeling, safety, manufacturing processes and/or other matters that could affect the availability or commercial potential of Ibrance or any other oncology products; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2018 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results,” as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.

_______________________________

  1. 1 FDA: Real World Evidence. https://www.fda.gov/scienceresearch/specialtopics/realworldevidence/default.htm. Accessed March 5, 2019.
  2. 2 American Cancer Society. Key statistics for breast cancer in men. https://www.cancer.org/cancer/breast-cancer-in-men/about/key-statistics.html. Accessed March 20, 2019.
  3. 3 FDA: 21st Century Cures Act. https://www.fda.gov/regulatoryinformation/lawsenforcedbyfda/significantamendmentstothefdcact/21stcenturycuresact/default.htm. Accessed March 5, 2019.
  4. 4 FDA: Real World Evidence. https://www.fda.gov/ScienceResearch/SpecialTopics/RealWorldEvidence/default.htm. Accessed March 5, 2019.
  5. 5 Pfizer global safety database.
  6. 6 Ibrance® (palbociclib) Prescribing Information. New York. NY: Pfizer Inc: 2019.
  7. 7 Weinberg, RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland Science; 2014:275-329.
  8. 8 Sotillo E, Grana X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010:3-22.

Source: Pfizer

Posted: April 2019

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FDA Approves Jatenzo (testosterone undecanoate) for Certain Forms of Hypogonadism

FDA Approves Jatenzo (testosterone undecanoate) for Certain Forms of Hypogonadism

March 27, 2019 — The U.S. Food and Drug Administration today approved Jatenzo (testosterone undecanoate), an oral testosterone capsule to treat men with certain forms of hypogonadism. These men have low testosterone levels due to specific medical conditions, such as genetic disorders like Klinefelter syndrome or tumors that have damaged the pituitary gland. Jatenzo should not be used to treat men with “age-related hypogonadism,” in which testosterone levels decline due to aging, even if these men have symptoms that appear to be related to low testosterone. Jatenzo’s benefits do not outweigh its risks for that use.

“Jatenzo’s oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who up until now have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, M.D, M.M.Sc., director of the Division of Bone, Reproductive and Urologic Products in the FDA’s Center for Drug Evaluation and Research. “But it’s important to emphasize that this drug should not, like other testosterone treatments, be used to treat older men with ‘age-related hypogonadism.’ The benefits of testosterone therapy, including Jatenzo, have not been established for this use, and Jatenzo’s effects on raising blood pressure can increase the risks of heart attack, stroke and cardiovascular death in this population.”

The efficacy of Jatenzo was demonstrated in a four-month clinical trial involving 166 men with hypogonadism. Study participants initially were given Jatenzo at a dose of 237 mg twice per day, and the dose was adjusted downward or upward to a maximum of 396 mg twice per day on the basis of testosterone levels. Eighty-seven percent of Jatenzo-treated men achieved an average testosterone level within the normal range, which was the primary study endpoint.

Jatenzo contains a boxed warning on its labeling stating that the drug can cause blood pressure to rise, increasing the risk of heart attack, stroke and cardiovascular death. Health care providers should consider a patient’s individual heart disease risks and ensure that blood pressure is adequately controlled before prescribing Jatenzo; they should also periodically monitor patient blood pressure during treatment. Jatenzo is currently one of two testosterone products that have this boxed warning. The FDA is requiring all testosterone product manufacturers to conduct blood pressure postmarketing trials to more clearly address whether these products increase blood pressure.

Common side effects, occurring in more than 2 percent of patients in the Jatenzo clinical trial, included headache, an increase in hematocrit (red blood cell count), a decrease in high-density lipoprotein cholesterol (“good” cholesterol), high blood pressure and nausea. An increase in prostate specific antigen (PSA) was also observed. Patients should have their hematocrit, cholesterol and PSA monitored regularly to check for changes. Those with benign prostate hyperplasia should be monitored for worsening of symptoms.

The FDA granted the approval of Jatenzo to Clarus Therapeutics.

Posted: March 2019

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FDA Approves Zulresso (brexanolone) for the Treatment of Postpartum Depression

FDA Approves Zulresso (brexanolone) for the Treatment of Postpartum Depression

March 19, 2019 — The U.S. Food and Drug Administration today approved Zulresso (brexanolone) injection for intravenous (IV) use for the treatment of postpartum depression (PPD) in adult women. This is the first drug approved by the FDA specifically for PPD.

“Postpartum depression is a serious condition that, when severe, can be life-threatening. Women may experience thoughts about harming themselves or harming their child. Postpartum depression can also interfere with the maternal-infant bond. This approval marks the first time a drug has been specifically approved to treat postpartum depression, providing an important new treatment option,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Because of concerns about serious risks, including excessive sedation or sudden loss of consciousness during administration, Zulresso has been approved with a Risk Evaluation and Mitigation Strategy (REMS) and is only available to patients through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient.”

PPD is a major depressive episode that occurs following childbirth, although symptoms can start during pregnancy. As with other forms of depression, it is characterized by sadness and/or loss of interest in activities that one used to enjoy and a decreased ability to feel pleasure (anhedonia) and may present with symptoms such as cognitive impairment, feelings of worthlessness or guilt, or suicidal ideation.

Zulresso will be available only through a restricted program called the Zulresso REMS Program that requires the drug be administered by a health care provider in a certified health care facility. The REMS requires that patients be enrolled in the program prior to administration of the drug. Zulresso is administered as a continuous IV infusion over a total of 60 hours (2.5 days). Because of the risk of serious harm due to the sudden loss of consciousness, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring (monitors oxygen levels in the blood). While receiving the infusion, patients must be accompanied during interactions with their child(ren). The need for these steps is addressed in a Boxed Warning in the drug’s prescribing information. Patients will be counseled on the risks of Zulresso treatment and instructed that they must be monitored for these effects at a health care facility for the entire 60 hours of infusion. Patients should not drive, operate machinery, or do other dangerous activities until feelings of sleepiness from the treatment have completely gone away.

The efficacy of Zulresso was shown in two clinical studies in participants who received a 60-hour continuous intravenous infusion of Zulresso or placebo and were then followed for four weeks. One study included patients with severe PPD and the other included patients with moderate PPD. The primary measure in the study was the mean change from baseline in depressive symptoms as measured by a depression rating scale. In both placebo controlled studies, Zulresso demonstrated superiority to placebo in improvement of depressive symptoms at the end of the first infusion. The improvement in depression was also observed at the end of the 30-day follow-up period.

The most common adverse reactions reported by patients treated with Zulresso in clinical trials include sleepiness, dry mouth, loss of consciousness and flushing. Health care providers should consider changing the therapeutic regimen, including discontinuing Zulresso in patients whose PPD becomes worse or who experience emergent suicidal thoughts and behaviors.

The FDA granted this application Priority Review and Breakthrough Therapy designation.

Approval of Zulresso was granted to Sage Therapeutics, Inc.

Source: FDA

Posted: March 2019

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FDA Approves Spravato (esketamine) Nasal Spray for Treatment-Resistant Depression

March 5, 2019 — The U.S. Food and Drug Administration today approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression). Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).

“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safey concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient.”

Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression.

The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they receved the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks.
The patient self-administers Spravato nasal spray under the supervision of a health care provider in a certified doctor’s office or clinic, and the spray cannot be taken home. The health care provider will instruct the patient on how to operate the nasal spray device. During and after each use of the nasal spray device, the health care provider will check the patient and determine when the patient is ready to leave.

The efficacy of Spravato was evaluated in three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato or a placebo nasal spray. In light of the serious nature of treatment-resistant depresison and the need for patients to receive some form of treatment, all patients in these studies started a new oral antidepressant at the time of randomization and the new antidepressant was continued throughout the trials. The primary efficacy measure was the change from baseline on a scale used to assess the severity of depressive symptoms. In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.

The most common side effects experienced by patients treated with Spravato in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.

Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Spravato may impair attention, judgment, thinking, reaction speed and motor skills. Patients should not drive or operate machinery until the next day after a restful sleep. Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated.

Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.

The FDA granted this application Fast Track and Breakthrough Therapy designations.

The FDA granted the approval of Spravato to Janssen Pharmaceuticals, Inc.

Posted: March 2019

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https://www.drugs.com/newdrugs/fda-approves-spravato-esketamine-nasal-resistant-depression-4926.html?utm_source=ddc&utm_medium=rss&utm_campaign=FDA+Approves+Spravato+%28esketamine%29+Nasal+Spray+for+Treatment-Resistant+Depression


FDA Approves Adhansia XR (methylphenidate hydrochloride) Extended-Release Capsules for the Treatment of ADHD

FDA Approves Adhansia XR (methylphenidate hydrochloride) Extended-Release Capsules for the Treatment of ADHD