FDA Approves Terlivaz (terlipressin) for the Treatment of Hepatorenal Syndrome (HRS)

Mallinckrodt plc (OTCMKTS: MNKPF), a global specialty pharmaceutical company,   announced  the U.S. Food and Drug Administration (FDA) approval of  Terlivaz (terlipressin) for injection. Terlivaz is the first and only FDA-approved product indicated to improve kidney function in adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function, an acute and life-threatening condition requiring hospitalization.

 

 

Please see Limitation of Use and Important Safety Information, including Boxed Warning, below.

Siggi Olafsson, President and Chief Executive Officer, said, "The FDA approval of Terlivaz is a significant milestone for Mallinckrodt as it brings an important treatment option to these critically ill patients requiring hospitalization and to U.S. physicians who historically have had limited treatment interventions. We're excited to bring Terlivaz to U.S. patients and physicians and plan to launch the product in the coming weeks. This approval reflects Mallinckrodt's continued commitment to underserved patients and their caregivers through our demonstrated expertise and dedication to developing therapeutics for critical conditions."

Terlipressin is recommended by the American Association for the Study of Liver Diseases (AASLD) guidance and the American College of Gastroenterology (ACG) guidelines.*^, Terlipressin is one of the most studied pharmacological agents in HRS with more than 70 published manuscripts and presented abstracts on clinical data to date. It has been approved outside the U.S. for more than 30 years and is available on five continents for its indications in the countries where it is approved.

The FDA approval was based, in part, on results from the Phase 3 CONFIRM trial, the largest-ever prospective study (n=300) conducted to assess the safety and efficacy of terlipressin in patients with HRS type 1 (HRS-1) in the U.S. and Canada. The CONFIRM trial met its primary endpoint of Verified HRS Reversal, defined as renal function improvement, avoidance of dialysis and short-term survival (p=0.012).  To achieve Verified HRS Reversal, patients had to have two consecutive serum creatinine (SCr) values of ≤1.5 mg/dL, at least two hours apart by day 14 or hospital discharge. To be included in the primary efficacy endpoint analysis, patients had to be alive and without intervening renal replacement therapy (e.g., dialysis) at least 10 days after achieving Verified HRS Reversal. Initial results were presented in a late-breaking session at The Liver Meeting^® 2019, the annual meeting of AASLD. Results were also published in the New England Journal of Medicine in March of 2021. The CONFIRM trial was completed prior to the updated diagnostic criteria and terminology published in the 2021 AASLD guidance on hepatorenal syndrome.

Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt said, "Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it. Terlivaz gives U.S. physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function¹ that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis."

The most commonly observed adverse reactions in at least 4 percent of patients treated with Terlivaz compared to placebo were abdominal pain reported in 19.5 percent (n=39) of patients (vs. 6.1%; n=6), nausea reported in 16 percent (n=32) of patients (vs. 10.1%; n=10), respiratory failure reported in 15.5 percent (n=31) of patients (vs. 7.1%; n=7) diarrhea reported in 13 percent (n=26) of patients (vs. 7.1%; n=7) and dyspnea reported in 12.5 percent (n=25) of patients (vs. 5.1%; n=5).¹

 

FDA Approves Aponvie (aprepitant) for the Prevention of Postoperative Nausea and Vomiting (PONV)

In continuation of my update on aprepitant

 

 

 

Heron Therapeutics, Inc., a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs,  announced  the U.S. Food and Drug Administration (FDA)   approval of  Aponvie (aprepitant) injectable emulsion, for intravenous use for the prevention of postoperative nausea and vomiting (PONV) in adults. 

Aponvie is the first and only IV formulation of aprepitant for PONV prevention. Administered via a single 30-second IV injection, Aponvie reaches drug levels associated with ≥97% receptor occupancy in the brain within five minutes and maintains therapeutic plasma concentrations for at least 48 hours. Aponvie is provided in a single-dose vial that delivers the full 32 mg dose approved for PONV. This ready-to-use, easy to administer, innovative IV formulation ensures rapid and consistent exposure in patients undergoing surgery.

An important component of the FDA approval of Aponvie were results from two multicenter, randomized, double-blind clinical studies comparing oral aprepitant to current standard of care, IV ondansetron, for the prevention of PONV in patients during the 48 hours following open abdominal surgery demonstrating that aprepitant was more effective than ondansetron in preventing vomiting. Treatment with aprepitant resulted in approximately 50% fewer patients vomiting in the first 24 and 48 hours compared to ondansetron. In clinical studies, Aponvie was well-tolerated and presented a safety profile comparable to oral aprepitant.

In a 2020 Cochrane meta-analysis, aprepitant was ranked as the most effective drug approved for PONV prophylaxis, being the most effective for the prevention of vomiting in the first 24 hours post-surgery and the drug with the fewest adverse events.

"With the approval of Aponvie our acute care portfolio now addresses the two most common concerns of patients and clinicians after surgery, postoperative pain and postoperative nausea and vomiting. This marks an important milestone for our expanding acute care portfolio and is a testament to our ongoing commitment to developing innovative solutions to help improve the overall patient experience after surgery," said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. "With approximately 36 million procedures in the U.S. each year in patients with high to moderate risk for PONV, the approval of Aponvie provides an easy to use, highly effective option for these patients that fits seamlessly into our acute care franchise."

PONV are common adverse effects of anesthesia and surgery, with an estimated 30 percent of patients receiving general anesthesia and up to 80 percent of high-risk patients experiencing these symptoms, necessitating more effective preventative agents. PONV is a major cause of patient dissatisfaction after surgery, with patients frequently ranking vomiting as the most undesirable outcome of anesthesia. Additionally, PONV presents a significant risk in outpatient surgeries as patients are often discharged within hours after surgery and no longer have access to highly effective antiemetics.

"PONV is commonly experienced after surgery and may result in increased hospital stays, prolonged recovery time, and decreased patient satisfaction" said Ashraf Habib, MBBCh, MSc, MHSc, FRCA, Chief, Division of Women's Anesthesia at Duke University Hospital. "Oral aprepitant has been used to prevent postoperative nausea and vomiting for more than 16 years and it is exciting to see that, with the approval of Aponvie, physicians can now offer patients a more convenient IV injection that delivers the same effective treatment, with a 48-hour duration of effect, in a rapid, consistent and reliable way, ensuring a better experience for patients postoperatively."
 
 

Acadia Pharmaceuticals Announces Trofinetide New Drug Application for the Treatment of Rett Syndrome has been Accepted for Filing and Review by U.S. FDA

About Rett Syndrome

Rett syndrome is a rare genetic neurodevelopmental disorder that occurs primarily in females following a near normal development in the first two years of life.  It is caused by mutations on the X chromosome on a gene called MECP2.  Occurring worldwide in approximately one of every 10,000 to 15,000 female births and in the United States impacts 6,000 to 9,000 patients.  Children with Rett syndrome experience a period of developmental regression between 18-30 months of age, which is typically followed by a plateau period lasting years to decades. Rett syndrome is diagnosed based on clinical evaluation, typically by about three years of age

A complex and multisystem disorder, Rett syndrome causes profound impairment to central nervous system (CNS) function, including loss of communication skills, purposeful hand use, gait abnormalities, and stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms.   People living with Rett syndrome may also experience a range of additional symptoms, such as gastrointestinal complications, skeletal abnormalities, neuroendocrine abnormalities, disruptive and anxiety-like behaviors, as well as mood dysregulation and sleep disturbances. Currently, there are no FDA-approved medicines for the treatment of Rett syndrome.

About Trofinetide

Trofinetide is an investigational drug. It is a novel synthetic analog of the amino‐terminal tripeptide of IGF-1 designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function. Trofinetide is thought to stimulate synaptic maturation and overcome the synaptic and neuronal immaturities that are characteristic of Rett syndrome pathophysiology. In the central nervous system, IGF-1 is produced by both of the major types of brain cells – neurons and glia. IGF-1 in the brain is critical for both normal development and for response to injury and disease. Trofinetide has been shown to inhibit the production of inflammatory cytokines, inhibit the overactivation of microglia and astrocytes, and increase the amount of available IGF-1 that can bind to IGF-1 receptors.

https://en.wikipedia.org/wiki/Trofinetide

Acadia Pharmaceuticals Inc.  announced   the U.S. Food and Drug Administration (FDA)  acceptance  for filing its New Drug Application (NDA) of trofinetide for the treatment of Rett syndrome. The FDA has granted a priority review and assigned a PDUFA (Prescription Drug User Fee Act) action date of March 12, 2023. The FDA has also informed the company that at this time they are not planning to hold an Advisory Committee meeting.

“We’re pleased that the FDA has accepted our NDA filing and we will be working closely with them to facilitate completion of the review in a timely manner,” said Steve Davis, Acadia’s Chief Executive Officer. “If approved, trofinetide will be the first drug available for the treatment of Rett syndrome, a rare and devastating condition for patients and their families. This milestone reinforces Acadia’s ongoing commitment to advancing research into high unmet needs in disorders affecting the central nervous system.”

Rett syndrome is a complex, multisystem neurodevelopmental disorder that includes a period of normal development followed by significant developmental regression with loss of language and hand function skills, impaired gait and development of hand stereotypes.1,2 It occurs worldwide in approximately one of every 10,000 to 15,000 female births.3

“Rett is a complex disease that can present with a diverse array of symptoms. In clinical trials, trofinetide demonstrated a significant improvement in a range of Rett syndrome symptoms,” said Jeffrey L. Neul, M.D., Ph.D., Annette Schaffer Eskind Chair and Director, Vanderbilt Kennedy Center, Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Phase 3 Lavender™ study investigator. “We look forward to the FDA’s review of this submission and the prospect of having access to the first approved treatment for Rett syndrome.”

The NDA is supported by results from the pivotal Phase 3 Lavender study evaluating the efficacy and safety of trofinetide versus placebo in 187 girls and young women aged 5-20 years with Rett syndrome. The study demonstrated a statistically significant improvement over placebo on the co-primary endpoints, the Rett Syndrome Behaviour Questionnaire (RSBQ) total score change from baseline to 12 weeks (p=0.0175; effect size=0.37) and the Clinical Global Impression-Improvement (CGI-I) scale score (p=0.0030; effect size=0.47). The RSBQ is a caregiver assessment of the core symptoms of Rett syndrome, and the CGI-I is a global physician assessment of worsening or improving of Rett syndrome. In addition, the study also met its key secondary endpoint, the Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist–Social Composite Score (CSBS-DP-IT–Social) change from baseline to week 12 (p=0.0064; effect size=0.43), a caregiver assessment of ability to communicate.

In 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals Limited (ASX: NEU) for the development and commercialization of trofinetide for the treatment of Rett syndrome and other indications in North America. In addition to receiving priority review by the FDA, trofinetide has been granted Fast Track Status and Orphan Drug Designation for the treatment of Rett syndrome in the U.S. and has been granted Rare Pediatric Disease (RPD) designation by the FDA. Upon FDA approval of a product with RPD designation, the sponsor can receive a Priority Review Voucher, which can be used to obtain priority review for a subsequent application.

FDA Approves Amvuttra (vutrisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the U.S. Food and Drug Administration (FDA) approved Amvuttra (vutrisiran), an RNAi therapeutic administered via subcutaneous injection once every three months (quarterly) for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. hATTR amyloidosis is a rare, inherited, rapidly progressive, and fatal disease with debilitating polyneuropathy manifestations, for which there are few treatment options. The FDA approval is based on positive 9-month results from the HELIOS-A Phase 3 study, where Amvuttra significantly improved the signs and symptoms of polyneuropathy, with more than 50 percent of patients experiencing halting or reversal of their disease manifestations.

“Twenty years ago, Alnylam was founded with the bold vision for RNA interference to make a meaningful impact on the lives of people around the world in need of new approaches to address serious diseases with significant unmet medical needs, such as hATTR amyloidosis. Today, Amvuttra has the potential to change the standard of care for people living with the polyneuropathy of this devastating disease,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam Pharmaceuticals. “We are so thankful to the patients, families and investigators involved in making Amvuttra a reality for the hATTR amyloidosis community. As the fifth RNAi therapeutic developed by Alnylam to receive regulatory approval in less than four years, we believe Amvuttra represents an important milestone that brings us one step closer to achieving our P5x25 goals aimed at Alnylam’s transition to a leading biotech company.”

The FDA approval of Amvuttra is based on positive 9-month results from HELIOS-A, a global, randomized, open-label, multicenter, Phase 3 study that evaluated the efficacy and safety of Amvuttra across a diverse group of patients with hATTR amyloidosis with polyneuropathy. 164 patients with hATTR amyloidosis were randomized 3:1 to receive either 25 mg of vutrisiran (N=122) via subcutaneous injection once every three months or 0.3 mg/kg of patisiran (N=42) via intravenous infusion once every three weeks (reference group) for 18 months. The efficacy of Amvuttra was assessed by comparing the Amvuttra group in HELIOS-A with the placebo group (n=77) from the landmark APOLLO Phase 3 study of patisiran, a randomized controlled study in a comparable patient population.

Amvuttra met the primary endpoint of the study, the change from baseline in the modified Neuropathy Impairment Score + 7 (mNIS+7) at 9 months. Treatment with Amvuttra (N=114) resulted in a 2.2 point mean decrease (improvement) in mNIS+7 from baseline as compared to a 14.8 point mean increase (worsening) reported for the external placebo group (N=67), resulting in a 17.0 point mean difference relative to placebo (p<0.0001); by 9 months, 50 percent of patients treated with Amvuttra experienced improvement in neuropathy impairment relative to baseline.

Amvuttra also met all secondary endpoints in the study at 9 months, with significant improvement in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) score and timed 10-meter walk test (10-MWT), and improvements were observed in exploratory endpoints, including change from baseline in modified body mass index (mBMI), all relative to external placebo. Efficacy results at 18 months were consistent with 9-month data, with Amvuttra achieving statistically significant improvements compared to external placebo for all secondary endpoints including mNIS+7, Norfolk QoL-DN, 10-MWT and mBMI, and non-inferiority in serum TTR reduction relative to the within-study patisiran reference group.

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FDA Approves Amvuttra (vutrisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults

FDA Approves Mounjaro (tirzepatide) Injection for the Treatment of Adults with Type 2 Diabetes

The U.S. Food and Drug Administration (FDA) has approved Mounjaro (tirzepatide) injection, Eli Lilly and Company's (NYSE: LLY) new once-weekly GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Mounjaro has not been studied in patients with a history of pancreatitis and is not indicated for use in patients with type 1 diabetes mellitus.

As the first and only FDA-approved GIP and GLP-1 receptor agonist, Mounjaro is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones.1

"Mounjaro delivered superior and consistent A1C reductions against all of the comparators throughout the SURPASS program, which was designed to assess Mounjaro's efficacy and safety in a broad range of adults with type 2 diabetes who could be treated in clinical practice. The approval of Mounjaro is an exciting step forward for people living with type 2 diabetes given the results seen in these clinical trials," said Juan Pablo Frías, M.D., Medical Director, National Research Institute and Investigator in the SURPASS program.

Mounjaro will be available in six doses (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg) and will come in Lilly's well-established auto-injector pen with a pre-attached, hidden needle that patients do not need to handle or see.

The approval was based on results from the phase 3 SURPASS program, which included active comparators of injectable semaglutide 1 mg, insulin glargine and insulin degludec. Efficacy was evaluated for Mounjaro 5 mg, 10 mg and 15 mg used alone or in combination with commonly prescribed diabetes medications, including metformin, SGLT2 inhibitors, sulfonylureas and insulin glargine. Participants in the SURPASS program achieved average A1C reductions between 1.8% and 2.1% for Mounjaro 5 mg and between 1.7% and 2.4% for both Mounjaro 10 mg and Mounjaro 15 mg. While not indicated for weight loss, mean change in body weight was a key secondary endpoint in all SURPASS studies. Participants treated with Mounjaro lost between 12 lb. (5 mg) and 25 lb. (15 mg) on average.1

Side effects reported in at least 5% of patients treated with Mounjaro include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion (dyspepsia), and stomach (abdominal) pain. The labeling for Mounjaro contains a Boxed Warning regarding thyroid C-cell tumors. Mounjaro is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2.1

"Lilly has a nearly 100-year heritage of advancing care for people living with diabetes – never settling for current outcomes. We're not satisfied knowing that half of the more than 30 million Americans living with type 2 diabetes are not reaching their target blood glucose levels," said Mike Mason, president, Lilly Diabetes. "We are thrilled to introduce Mounjaro, which represents the first new class of type 2 diabetes medication introduced in almost a decade and embodies our mission to bring innovative new therapies to the diabetes community."

More at 

https://www.rxlist.com/mounjaro-drug.htm

FDA Approves Radicava ORS (edaravone) for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

Mitsubishi Tanabe Pharma Corporation (MTPA)   announced the U.S. Food and Drug Administration (FDA)   approval of Radicava ORS (edaravone), the oral form of edaravone, for the treatment of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that currently has no cure and can progress rapidly.  Radicava ORS offers the same efficacy as Radicava (edaravone), an FDA-approved intravenous (IV) treatment shown in a pivotal trial to help slow the loss of physical function in ALS. 

"At MTPA, patients have been the driving force behind our work as we strive to develop meaningful treatment options for ALS and continue to tackle unmet needs," said Atsushi Fujimoto, President, MTPA. "Five years ago, we proudly launched Radicava as a treatment option for patients with ALS in the U.S. Now, we continue to push the boundaries of innovation with Radicava ORS, an orally administered option allowing patients flexibility in how they take their medicine."

Radicava ORS is specifically formulated for patients with ALS and provides a flexible administration option (taken orally or via feeding tube) with a small, 5 mL dose, a portable bottle, an oral dosing syringe and no need for patients to refrigerate or reconstitute before taking.1 With appropriate instruction from a healthcare provider (HCP), Radicava ORS may take only a few minutes to administer on treatment days.1 Radicava ORS should be taken in the morning after overnight fasting.1 To learn more about Radicava ORS, visit Radicava.com/update.

"ALS is a progressive disease that, due to its heterogenous nature, impacts patients at different rates with varying symptoms," said Tulio Bertorini, M.D., Professor of Neurology, The University of Tennessee Health Science Center. "Therefore, it is crucial that patients have treatment and formulation options that accommodate their own unique needs, and Radicava ORS provides HCPs who have prescribed their ALS patients edaravone with an alternate delivery option."

The comprehensive clinical development program for edaravone in ALS has spanned over a decade and included multiple clinical trials for the IV and oral formulations. The FDA approval of Radicava ORS is supported by several studies, including data from the pivotal Phase 3 clinical trial (MCI186-19) evaluating 137 ALS patients that showed treatment with Radicava slowed the loss of physical function by 33 percent (approximately one-third) compared to placebo at 24 weeks, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), a validated rating instrument for monitoring disease progression in patients.1Additionally, seven Phase 1 clinical pharmacology studies were conducted to examine the pharmacokinetics, safety, drug-to-drug interactions, dosing, bioavailability and bioequivalence of Radicava ORS in healthy individuals and ALS patients with and without a percutaneous endoscopic gastrostomy (PEG) tube/nasogastric (NG) tube, as well as a global Phase 3, 24-week trial demonstrating the safety and tolerability profile of the treatment in 185 patients with ALS. Lastly, there is an ongoing Phase 3 study evaluating the long-term safety and tolerability of Radicava ORS for up to 96 weeks.

The most common adverse events that occurred in greater than 10 percent of patients treated with Radicava were bruising (contusion), problems walking (gait disturbance) and headache. Fatigue was observed in 7.6 percent of patients taking Radicava ORS.  Radicava and Radicava ORS are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product.1 Hypersensitivity reactions and anaphylactic reactions have been reported in patients treated with Radicava.

More at..

https://en.wikipedia.org/wiki/Edaravone

Voquezna Triple Pak (amoxicillin, clarithromycin, and vonoprazan) FDA Approval

The Voquezna Triple and Dual Paks offer physicians the flexibility of two different treatment options. The Voquezna Triple Pak contains clarithromycin that is not included in the Voquezna Dual Pak.

Voquezna Triple Pak (amoxicillin, clarithromycin, and vonoprazan) is a co-packaged product containing amoxicillin (penicillin class antibacterial), clarithromycin (macrolide antimicrobial), and vonoprazan (potassium-competitive acid blocker (PCAB)) indicated for the treatment of Helicobacter pylori (H. pylori) infection in adults.

More 

https://en.wikipedia.org/wiki/Amoxicillin

https://en.wikipedia.org/wiki/Clarithromycin

https://en.wikipedia.org/wiki/Vonoprazan

FDA Approves Camzyos (mavacamten) for the Treatment of Symptomatic NYHA Class II-III Obstructive Hypertrophic Cardiomyopathy

In continuation of my update on mavacamten

Bristol Myers Squibb (NYSE: BMY)  announced  the U.S. Food and Drug Administration (FDA) approval of  Camzyos (mavacamten, 2.5 mg, 5 mg, 10 mg, 15 mg capsules) for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (obstructive HCM) to improve functional capacity and symptoms. Camzyos is the first and only FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of obstructive HCM.

“This is a first-in-class medicine specifically for patients living with symptomatic obstructive HCM,” said Milind Desai, M.D., MBA, director of the Hypertrophic Cardiomyopathy Center and director of clinical operations in Cleveland Clinic’s Heart Vascular & Thoracic Institute. "With this FDA approval, U.S. cardiologists now have a new pharmacological option for eligible patients that targets the underlying pathophysiology of the disease.”

The full U.S. Prescribing Information for Camzyos includes a Boxed WARNING for the risk of heart failure. Camzyos reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. Echocardiogram assessments of LVEF are required prior to and during treatment with Camzyos. Initiation of Camzyos in patients with LVEF <55% is not recommended. Interrupt Camzyos if LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status. Concomitant use of Camzyos with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of Camzyos is contraindicated with moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers. Because of the risk of heart failure due to systolic dysfunction, Camzyos is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Camzyos REMS PROGRAM. Please see additional Important Safety Information including Boxed WARNING below.

“This approval builds on decades of cardiovascular leadership and reflects our steadfast commitment to people impacted by cardiovascular disease,” said Samit Hirawat, M.D., executive vice president and chief medical officer, Global Drug Development, Bristol Myers Squibb. “We are proud to bring this first-of-its kind medicine to patients, which may help to address an unmet need in the U.S. in the symptomatic NYHA class II-III obstructive HCM treatment landscape.”

This approval is based on data from the Phase 3 EXPLORER-HCM trial. At baseline, approximately 73% of the randomized patients were NYHA class II and 27% were NYHA class III. The mean LVEF was 74%, and the mean Valsalva left ventricular outflow tract (LVOT) gradient was 73 mmHg. The baseline mean Kansas City Cardiomyopathy Questionaire-23 (KCCQ-23) Clinical Summary Score (CSS) was 71. At Week 30, 37% (n=45/123) of patients taking Camzyos achieved the composite primary endpoint, defined as the proportion of patients who achieved either improvement of mixed venous oxygen tension (pVO2) by ≥1.5 mL/kg/min plus improvement in NYHA class by at least 1 or improvement of pVO2 by ≥3.0 mL/kg/min plus no worsening in NYHA class, versus 17% (n=22/128) treated with placebo. The difference was 19% (95% CI: 9, 30; p=0.0005). Additionally at Week 30, patients receiving Camzyos had greater improvement compared to placebo group across all secondary endpoints, including:

• Mean change from baseline post-exercise LVOT peak gradient [-47 mmHg vs -10 mmHG; -35 difference (95% CI: -43, -28; p<0.0001)]
• Mean change from baseline in pVO2 [1.4 mL/kg/min vs -0.1 mL/kg/min; 1.4 difference (95% CI: 0.6, 2.1; p<0.0006)]
• Number (%) of patients with improvement of NYHA class ≥ 1 [80 (65%) vs 40 (31%); difference of 34% (95% CI; 22%, 45%; p<0.0001)]
• Mean change from baseline in KCCQ-23 † CSS [14 vs 4; difference of 9 (95% CI: 5, 13); p<0.0001]
  • Mean change in baseline in KCCQ-23 Total Symptom Score (TSS) (12 vs 5)
  • Mean change in baseline in KCCQ-23 Physical Limitations (PL) (15 vs 4)

  •  The KCCQ-23 CSS is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ-23. The CSS ranges from 0 to 100 with higher scores representing less severe symptoms and/or physical limitations.

    Missing data were not imputed to summarize the baseline and change from baseline to Week 30 values. Difference in mean change from baseline between treatment groups was estimated using a mixed model for repeated measures.

  • In the EXPLORER-HCM trial, adverse reactions occurring in >5% of patients and more commonly in the Camzyos group than in the placebo group were dizziness (27% vs 18%) and syncope (6% vs 2%). Mean (SD) resting LVEF was 74% (6) at baseline in both treatment groups. Mean (SD) absolute change from baseline in LVEF was -4% (8) in the Camzyos group and 0% (7) in the placebo group over the 30-week treatment period. At Week 38, following an 8-week interruption of trial drug, mean LVEF was similar to baseline for both treatment groups. Additionally, 7 (6%) patients in the Camzyos group and 2 (2%) patients in the placebo group experienced reversible reductions in LVEF to <50% (median 48%: range 35-49%) while on treatment. In all 7 patients treated with Camzyos, LVEF recovered following interruption of Camzyos.

    “The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” said Anjali T. Owens, MD, Medical Director of the Center for Inherited Cardiac Disease and an Assistant Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania. “As a lead U.S. investigator on the EXPLORER-HCM study, I’m grateful to the patients and their families whose participation in the trial played a key role in this approval.”

    Bristol Myers Squibb offers various programs and resources to address the needs of patients and caregivers, and provide support that allows for access to therapies, including Camzyos. For additional information, call 855-Camzyos (855-226-9967) 8 am to 11 pm ET, Monday through Friday.

https://en.wikipedia.org/wiki/Mavacamten