FDA Approves Gavreto (pralsetinib) for the Treatment of Adults With Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),  announced  the U.S. Food and Drug Administration (FDA) approval of Gavreto (pralsetinib) for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test. This indication was approved under the FDA’s accelerated approval program based on data from the Phase I/II ARROW study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations.

“The FDA approval of Gavreto for RET fusion-positive non-small cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We remain committed to finding personalized treatment options for people with cancer based on specific genomic or molecular alterations, and we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumor types.”

RET-activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and medullary thyroid cancer (MTC), and treatment options that selectively target these genetic alterations are limited. In NSCLC, RET fusions represent approximately 1-2% of patients. Biomarker testing for these fusions is the most effective way to identify people who are eligible for treatment with Gavreto.

The approval is based on the results from the Phase I/II ARROW study, in which Gavreto produced durable clinical responses in people with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement. Gavreto demonstrated an overall response rate (ORR) of 57% (95% CI: 46%, 68%) and complete response (CR) rate of 5.7% in the 87 people with NSCLC previously treated with platinum-based chemotherapy, and the median duration of response (DoR) was not reached (95% CI: 15.2 months, not reached). In the 27 people with treatment-naïve NSCLC, the ORR was 70% (95% CI: 50%, 86%) with an 11% CR rate. The most common adverse reactions (≥25%) were fatigue, constipation, musculoskeletal pain and increased blood pressure (hypertension).

Gavreto is now the sixth FDA-approved medicine in Genentech’s portfolio of treatments for lung cancer. The FDA granted Breakthrough Therapy Designation to Gavreto for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

The FDA has also granted Priority Review to Gavreto for the treatment of people with advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer, and is expected to make a decision on approval by February 28, 2021. This New Drug Application (NDA) was accepted for review under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

For those who qualify, Blueprint Medicines will offer patient assistance programs for people prescribed Gavreto by their doctor through YourBlueprint™ . Please visit www.yourblueprint.com or contact 1-888-BLUPRNT for more information.

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

FDA Approves Gavreto (pralsetinib) for the Treatment of Adults With Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

FDA Approves Sesquient (fosphenytoin sodium) for the Treatment of Status Epilepticus in Adult and Pediatric Patients

Sedor Pharmaceuticals, LLC (Sedor) announced the U.S. Food and Drug Administration (FDA) spproval of  Sesquient (fosphenytoin sodium for injection) for the treatment of status epilepticus in adult and pediatric patients.

According to Neurocritical Care Society Guidelines, status epilepticus, which is classified as a single epileptic seizure lasting more than five minutes or two or more seizures within a five-minute period, must be treated quickly since irreversible brain damage or death may result if cessation of seizure is not achieved within 60 minutes of onset. Ready-to-dilute and room temperature stable, Sesquient is the only FDA-approved fosphenytoin that allows point-of-care storage, as well as fast and efficient administration in emergency rooms, intensive care units, first responder vehicles, and long-term care facilities, where serial seizures such as status epilepticus are most commonly treated.

“Status epilepticus is associated with irreversible neurologic damage and death, both of which largely depend on the seizure duration before initial treatment,” stated Barry Frankel, Chief Business Officer and co-founder of Sedor. “At some hospitals, it can take up to 30 minutes to get a status epilepticus drug from the pharmacy to the point of care in the ER to treat a patient. Sesquient – the first and only FDA-approved room temperature stable fosphenytoin – could help health care providers quickly treat status epilepticus patients and potentially reduce hospital costs associated with this condition.”

“This is an important milestone for Sedor Pharmaceuticals and opens a significant global market for the company. As our first NDA approved drug, Sesquient validates our business model of efficient development of critical care hospital injectable products,” added John Sedor, Chairman, CEO and co-founder of Sedor. Mr. Sedor added “While Sesquient is available in pre-filled liquid vials, this is a multi-dosage platform which we believe will be followed by a pre-filled IV bag. With this achievement completed, we are turning our focus to the development of our second product, Meloxicam for injection solubilized with betadex sulfobutyl ether sodium, for the potential treatment of acute post-surgical pain.”

Sedor is actively engaged in discussions to license the rights to Sesquient for North America, Europe, and other territories except for the Peoples Republic of China, where it has already been successfully licensed. Concurrently, Sedor is in discussions on securing capital to retain North American rights and commercialize the product.

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

FDA Approves Sesquient (fosphenytoin sodium) for the Treatment of Status Epilepticus in Adult and Pediatric Patients

FDA Approves Detectnet (copper Cu 64 dotatate injection) Positron Emission Tomography (PET) Agent

RadioMedix Inc. and its commercial partner Curium announced the approval of  Detectnet (copper Cu 64 dotatate injection)  by the U.S. Food and Drug Administration (FDA).  Detectnet is a positron emission tomography (PET) agent indicated for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult patients.  Curium expects to launch Detectnet immediately with doses available through various nuclear pharmacies or directly from Curium.   

RadioMedix Inc. and its commercial partner Curium announced today that Detectnet (copper Cu 64 dotatate injection) was approved by the U.S. Food and Drug Administration (FDA).  Detectnet is a positron emission tomography (PET) agent indicated for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult patients.  Curium expects to launch Detectnet immediately with doses available through various nuclear pharmacies or directly from Curium.   

“Detectnet brings an exciting advancement in the diagnosis of neuroendocrine tumors for healthcare providers, patients, and their caregivers,” said Ebrahim Delpassand, MD, CEO of RadioMedix.  “The Phase III results demonstrate the clinical sensitivity and specificity of Detectnet which will provide a great aid to clinicians in developing an accurate treatment approach for their NET patients.  Perhaps most exciting is that the 12.7-hour half-life allows Detectnet to be produced centrally and shipped to sites throughout the U.S.  This will help alleviate shortages or delays that have been experienced with other somatostatin analogue PET agents.” 

“Curium is excited to bring the first commercially available Cu 64 diagnostic agent to the U.S. market.  Our unique production capabilities and distribution network allow us to deliver to any nuclear pharmacy, hospital or imaging center its full dosing requirements first thing in the morning, to provide scheduling flexibility to the institution and its patients,” said Curium CEO, North America, Dan Brague.  “We look forward to joining with healthcare providers and our nuclear pharmacy partners to bring this highly efficacious agent to the market.”      

“Detectnet brings an exciting advancement in the diagnosis of neuroendocrine tumors for healthcare providers, patients, and their caregivers,” said Ebrahim Delpassand, MD, CEO of RadioMedix.  “The Phase III results demonstrate the clinical sensitivity and specificity of Detectnet which will provide a great aid to clinicians in developing an accurate treatment approach for their NET patients.  Perhaps most exciting is that the 12.7-hour half-life allows Detectnet to be produced centrally and shipped to sites throughout the U.S.  This will help alleviate shortages or delays that have been experienced with other somatostatin analogue PET agents.” 

“Curium is excited to bring the first commercially available Cu 64 diagnostic agent to the U.S. market.  Our unique production capabilities and distribution network allow us to deliver to any nuclear pharmacy, hospital or imaging center its full dosing requirements first thing in the morning, to provide scheduling flexibility to the institution and its patients,” said Curium CEO, North America, Dan Brague.  “We look forward to joining with healthcare providers and our nuclear pharmacy partners to bring this highly efficacious agent to the market.”      

https://en.wikipedia.org/wiki/Copper_(64Cu)_oxodotreotide

FDA Approves Detectnet (copper Cu 64 dotatate injection) Positron Emission Tomography (PET) Agent

FDA Approves Qdolo (tramadol hydrochloride) Oral Solution for the Management of Severe Pain

In continuation of my update on tramadol 

Bioscience, LLC, a specialty pharmaceutical company, announced today that the U.S. Food and Drug Administration (FDA) has approved Qdolo™ (tramadol hydrochloride) Oral Solution 5mg/1mL C-IV, an opioid agonist indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

According to the Centers for Disease Control and Prevention, 50 million adults in the United States have chronic daily pain, with 19.6 million adults experiencing high-impact chronic pain that interferes with daily life or work activities. A May, 2019 U.S. Department of Health and Human Services report on pain management best practices emphasized the need for an "individualized, patient-centered" approach for the treatment of pain.1

"As an oral liquid, Qdolo gives physicians flexibility to titrate dosing precisely according to individual patients' needs," said Jeff Bryant, President and CEO of Athena Bioscience. "In addition, for patients with swallowing disfunction (dysphagia) or who simply have trouble swallowing pills, Qdolo provides an essential alternative to other forms of tramadol." Qdolo has a patent pending.

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

FDA Approves Qdolo (tramadol hydrochloride) Oral Solution for the Management of Severe Pain

FDA Approves Onureg (azacitidine tablets) as Continued Treatment for Adults in First Remission with Acute Myeloid Leukemia

Bristol Myers Squibb (NYSE: BMY) announced that the U.S. Food and Drug Administration (FDA) has approved Onureg (azacitidine 300 mg tablets, CC-486) for the continued treatment of adult patients with acute myeloid leukemia (AML) who achieved first complete remission (CR) or CR with incomplete blood count recovery (CRi) following intensive induction chemotherapy and who are not able to complete intensive curative therapy.  AML is one of the most common acute leukemias in adults.

The approval is based on results from the pivotal Phase 3 QUAZAR® AML-001 study in which treatment with Onureg resulted in a statistically significant and clinically meaningful improvement in overall survival (OS), the study’s primary endpoint, of nearly 10 months compared to placebo. Median OS from time of randomization was greater than two years (24.7 months; 95% Confidence Interval [CI]: 18.7 to 30.5) among patients who received Onureg compared to 14.8 months (95% CI: 11.7 to 17.6) among patients receiving placebo (Hazard Ratio [HR]: 0.69, 95% CI: 0.55 to 0.86; p=0.0009). Onureg was continued until disease progression or unacceptable toxicity. Onureg has warnings and precautions for risks of substitution with other azacitidine products, myelosuppression, increased early mortality in patients with myelodysplastic syndromes (MDS) and embryo-fetal toxicity. Due to substantial differences in the pharmacokinetic parameters, Onureg should not be substituted for intravenous or subcutaneous azacitidine as it may result in a fatal adverse reaction. New or worsening Grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received Onureg, respectively. Febrile neutropenia occurred in 12% of patients. Complete blood counts should be monitored, dosing should be modified as recommended and standard supportive care should be provided if myelosuppression occurs. Enrollment was discontinued early in the study AZA-MDS-003 due to a higher incidence of early fatal and/or serious adverse reactions in the Onureg arm compared with the placebo arm. Treatment of MDS with Onureg is not recommended outside of controlled trials. Onureg can cause fetal harm when administered to a pregnant woman.

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

FDA Approves Onureg (azacitidine tablets) as Continued Treatment for Adults in First Remission with Acute Myeloid Leukemia

AHA: Adding Omega-3 Fatty Acids Does Not Cut High CV Risk

In continuation of my update on omega-3 fatty acids

A carboxylic acid formulation of eicosapentaenoic acid and docosahexaenoic acid (omega-3 CA) does not improve outcomes among statin-treated patients at high cardiovascular risk, according to a study published online Nov. 15 in the Journal of the American Medical Association to coincide with the American Heart Association Scientific Sessions 2020, held virtually from Nov. 13 to 17.

Stephen J. Nicholls, M.B.B.S., Ph.D., from Monash University in Melbourne, Australia, and colleagues conducted a double-blind trial comparing omega-3 CA to corn oil in 13,078 statin-treated patients with high cardiovascular risk, hypertriglyceridemia, and low high-density lipoprotein cholesterol from 675 academic and community hospitals in 22 countries. Participants were randomly assigned in a 1:1 ratio to either 4 g/day omega-3 CA or corn oil (6,539 to each) in addition to usual background therapies, including statins.

The trial was halted prematurely based on an interim analysis indicating low probability of clinical benefit of omega-3 CA, when 1,384 patients had experienced a primary end-point event. The researchers found that the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization) occurred in 12.0 and 12.2 percent of those treated with omega-3 CA and corn oil, respectively (hazard ratio, 0.99; 95 percent confidence interval, 0.90 to 1.09; P = 0.84).

"These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including AstraZeneca, which funded the study.

AHA: Adding Omega-3 Fatty Acids Does Not Cut High CV Risk  

Drug eases recovery for those with severe alcohol withdrawal

A drug once used to treat high blood pressure can help alcoholics with withdrawal symptoms reduce or eliminate their drinking, Yale University researchers report Nov. 19 in the American Journal of Psychiatry.

In continuation of my update on prazosin 

In a double-blind study, researchers gave the drug prazosin or a placebo to 100 people entering outpatient treatment after being diagnosed with alcohol use disorder. All of the patients had experienced varying degrees of withdrawal symptoms prior to entering treatment.

According to the researchers, subjects with more severe symptoms -- including shakes, heightened cravings and anxiety, and difficulty sleeping -- who received prazosin significantly reduced the number of heavy drinking episodes and days they drank compared to those who received a placebo. The drug had little effect on those with few or no withdrawal symptoms.

"There has been no treatment readily available for people who experience severe withdrawal symptoms and these are the people at highest risk of relapse and are most likely to end up in hospital emergency rooms," said corresponding author Rajita Sinha, the Foundations Fund Professor of Psychiatry, a professor of neuroscience, and director of the Yale Stress Center.

Prazosin was originally developed to treat high blood pressure and is still used to treat prostate problems in men, among other conditions. Previous studies conducted at Yale have shown that the drug works on stress centers in the brain and helps to improve working memory and curb anxiety and craving.

Sinha's lab has shown that stress centers of the brain are severely disrupted early in recovery, especially for those with withdrawal symptoms and high cravings, but that the disruption decreases the longer the person maintains sobriety. Prazosin could help bridge that gap by moderating cravings and withdrawal symptoms earlier in recovery and increasing the chances that patients refrain from drinking, she said.

One drawback is that in its current form prazosin needs to be administered three times daily to be effective, Sinha noted.

The study was conducted at the Yale Stress Center and the Connecticut Mental Health Center's Clinical Neuroscience Research Unit. It was supported by the National Institute of Alcoholism and Alcohol Abuse at the National Institutes of Health and the Connecticut State Department of Mental Health and Addiction Services.

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

Drug eases recovery for those with severe alcohol withdrawal 

FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19

In continuation of my update on baricitinib and remdesivir

Emergency use authorization was issued for baricitinib in combination with remdesivir for hospitalized patients with COVID-19, the U.S. Food and Drug Administration announced Thursday.

                               

The EUA for the combination treatment applies to hospitalized patients ages 2 years and older with suspected or laboratory-confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. The janus kinase inhibitor baricitinib is currently FDA-approved for treating moderately to severely active rheumatoid arthritis.

Based on the agency's review of the evidence, the FDA "determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population. And, when used under the conditions described in the EUA to treat COVID-19, the known and potential benefits of baricitinib outweigh the known and potential risks for the drug."

The FDA granted the EUA based on data from the ACTT-2 trial, a randomized, double-blind, placebo-controlled clinical trial conducted by the National Institute of Allergy and Infectious Diseases. The trial included 1,033 patients -- 515 randomly assigned to baricitinib plus remdesivir and 518 randomly assigned to placebo plus remdesivir. Patients were followed for 29 days. Median time to recovery from COVID-19 was seven and eight days for patients receiving baricitinib plus remdesivir and those receiving placebo plus remdesivir, respectively. Patients receiving baricitinib plus remdesivir had significantly lower odds of progressing to death or being ventilated at 29 days and significantly higher odds of clinical improvement at 15 days compared with patients receiving placebo plus remdesivir.

Baricitinib is not authorized or approved as a stand-alone treatment for COVID-19, the FDA notes. Its safety and effectiveness for use in the treatment of COVID-19 continue to be evaluated.

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

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

FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19  

Early treatment with lorlatinib improves survival in some lung cancer patients: Lung cancer patients with a specific genetic alteration lived longer and were protected against metastasis to the brain when treated early with lorlatinib

In continuation of my update on Lorlatinib

Non-small-cell lung cancer (NSCLC) accounts for 87% of all cases of lung cancer. Some 5% of NSCLC cases are ALK-positive, which means they have a genetic abnormality in the anaplastic lymphoma kinase gene. ALK-positive NSCLC, which is not associated with smoking, is a particularly aggressive form of lung cancer.

"When ALK is turned on abnormally, it's like stepping on the gas pedal -- it drives uncontrolled proliferation and survival of cancer cells," says investigator Alice Shaw, MD, PhD, who was formerly director of the Center for Thoracic Cancers at MGH and led the NEJM study. Notably, ALK-positive patients tend to be 10 to 15 years younger than other lung cancer patients. They are also at high risk for developing brain metastasis.

A new class of drugs that block ALK, known as ALK inhibitors, was discovered in 2008. "Turning off ALK with an ALK inhibitor is like putting on the brakes," agrees Justin Gainor, MD, of the Mass General Cancer Center, who worked with Shaw on the study. "It can lead to rapid killing of cancer cells and cause tumors to shrink dramatically." Both first and second generation ALK inhibitors have been developed, including crizotinib (Xalkori), alectinib (Alecensa), and brigatinib (Alunbrig), which can be very effective, but patients eventually relapse. What's more, patients treated with these drugs can still develop metastatic spread of cancer to the brain.

Lorlatinib belongs to a third-generation of this drug class and is even more effective at blocking ALK. It's currently approved by the Food and Drug Administration for treating ALK-positive patients whose cancer has progressed despite taking older-generation ALK inhibitors.

Shaw and her co-investigators wanted to know if lorlatinib improved the likelihood of long-term remission in ALK-positive patients when administered as first-line therapy. To find out, she and colleagues at 104 medical centers in 23 countries recruited 296 patients with advanced, previously untreated ALK-positive NSCLC. Half of the patients received lorlatinib, while the remainder were treated with crizotinib, which was the standard of care for these patients when the trial began.

The results were striking. Compared to patients who received crizotinib, those given lorlatinib had a 72% reduction in the risk of cancer progression or death. Importantly, lorlatinib also reduced the risk of new or recurrent brain metastases by 93%. Serious side effects were more common in the lorlatinib group, but more than half were increases in blood cholesterol and triglycerides, which were manageable with medication.

The investigators will continue to follow patients in this study to track their long-term outcomes, but "these results support lorlatinib as a potential first-line option for ALK-positive patients," says Shaw.

Shaw is now global head of Translational Clinical Oncology at the Novartis Institutes for BioMedical Research

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

Early treatment with lorlatinib improves survival in some lung cancer patients: Lung cancer patients with a specific genetic alteration lived longer and were protected against metastasis to the brain when treated early with lorlatinib -- ScienceDaily

FDA Approves Xaracoll (bupivacaine hydrochloride) Implant for Acute Postsurgical Pain Relief Following Open Inguinal Hernia Repair

In continuation of my update on bupivacaine 

Innocoll Holdings Limited, a specialty pharmaceutical company and portfolio business of Gurnet Point Capital, announced today that the US Food and Drug Administration (FDA) has approved Xaracoll  for acute postsurgical pain relief for up to 24 hours in adults following open inguinal hernia repair, a painful and commonly-performed surgery.1  

Xaracoll is a unique, non-injectable drug-device combination in the form of a fully bioresorbable collagen implant containing bupivacaine hydrochloride. Xaracoll is placed directly into the surgical site during surgery and, after placement, releases bupivacaine immediately and over time.1,2

“Xaracoll is an advancement in the management of postsurgical pain as it is the first and only drug-device combination product to provide local pain relief following open inguinal hernia repair in adults,” said Innocoll CEO Rich Fante. “The FDA approval is an important milestone for Innocoll and we are excited to bring Xaracoll to market later this year as an effective and well-tolerated, non-opioid treatment option for surgeons.”

The efficacy and safety of Xaracoll was evaluated in two Phase III studies of identical design in open inguinal hernia repair. The Phase III studies were performed as outpatient surgeries in adults across 39 sites (N=610, Xaracoll Arm N=404, Placebo Arm N=206) in the US. Xaracoll provided statistically significant pain relief through 24 hours versus placebo, the primary endpoint for both studies. The first secondary endpoint of total use of opioid analgesia through 24 hours was also statistically significant. Additionally, the proportion of patients who did not receive opioid rescue analgesia through 72 hours in the Xaracoll and placebo treatment groups was 36% and 22%, respectively, in Study 1, and 28% and 12%, respectively, in Study 2.  The median time to first opioid rescue analgesia in the Xaracoll and placebo treatment groups was 11 hours and 1 hour, respectively, in Study 1, and 6 hours and 1 hour, respectively in Study 2. The most common adverse reactions in clinical trials (incidence ≥2% and higher than placebo) included incision site swelling, dysgeusia, headache, tremor, blurred vision, seroma, scrotal swelling, pyrexia, oral hypoesthesia, and post procedural discharge.1,3

“In Phase III studies Xaracoll was shown to provide local pain relief in patients undergoing open inguinal hernia repair while also decreasing the amount of opioids needed,” said Wendy Niebler DO, MBA, Chief Medical Officer at Innocoll. “We look forward to sharing our Phase III data with surgeons as we introduce this new option to manage acute pain following open inguinal hernia repair in adults.”  

INDICATIONS AND USAGE

Xaracoll contains an amide local anesthetic and is indicated in adults for placement into the surgical site to produce postsurgical analgesia for up to 24 hours following open inguinal hernia repair.

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

FDA Approves Xaracoll (bupivacaine hydrochloride) Implant for Acute Postsurgical Pain Relief Following Open Inguinal Hernia Repair

FDA Approves Winlevi (clascoterone) Cream for the Treatment of Acne

Cassiopea SpA (SIX: SKIN),  announced   the United States Food and Drug Administration (FDA) approval of  Winlevi (clascoterone cream 1%) for the treatment of acne in patients 12 years and older. Notwithstanding acne being the most prevalent skin condition in the U.S. affecting up to 50 million Americans annually1, the last FDA approval of an acne drug with a new mechanism of action (MOA) occurred nearly 40 years ago.

Acne is a multifactorial skin condition, affected by four distinct pathways: excess oil (sebum) production, clogged pores (hyperkeratinization), bacteria growth (C. acnes), and inflammation2. Topical treatment options that target androgens, which largely drive sebum production and inflammation, presented a significant unmet need in the acne treatment market until now.

“The approval of Winlevi is an exciting breakthrough in acne treatment. This game-changing topical drug offers a non-antibiotic approach to people with acne, by targeting the androgen receptors directly in the skin. It fills a longstanding gap in acne therapy.” said Michael Gold, M.D., Investigator and Medical Director, Gold Skin Care Center and Tennessee Clinical Research Center. “After 40 years, it provides a much-anticipated, complementary new approach to treat acne.”

Cassiopea’s first-in-class topical androgen receptor inhibitor, Winlevi, tackles the androgen hormone component of acne in both males and females. Androgen receptor inhibitors act by limiting the effects of these hormones on increasing sebum production and inflammation3.

In pivotal clinical trials, Winlevi demonstrated treatment success and reductions in acne lesions and was well tolerated when used twice a day. The most frequently observed local skin reaction was mild erythema4,5.

Diana Harbort, CEO of Cassiopea, said: “This milestone approval marks the introduction of a new class of topical medication in Dermatology. Dermatologists have said targeting androgen hormonal activity in the skin is ‘the holy grail’ of acne treatment for both males and females. We are proud to bring this new innovation to acne patients. This approval rewards many years of hard work and positions Cassiopea as a leader in Dermatology. Now we look forward to expanding our franchise and advancing our next investigational drug candidate for androgenetic alopecia.”

Winlevi is expected to be available in the United States in early 2021. Complete prescribing information is available on www.WINLEVI.com.

About Winlevi (clascoterone cream 1%)

Winlevi (clascoterone cream 1%) is approved for the treatment of acne vulgaris in people aged 12 and older. Although Winlevi’s exact mechanism of action is unknown, laboratory studies suggest the active ingredient, clascoterone, competes with androgens, specifically dihydrotestosterone (DHT), for binding to the androgen receptors within the sebaceous gland and hair follicles6.

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

FDA Approves Winlevi (clascoterone) Cream for the Treatment of Acne

Cow's Milk Intake While Breastfeeding May Cut Child Food Allergies

In continuation of my update on cow milk

Children whose mothers drink more cow's milk during breastfeeding are at a lower risk for developing food allergies, according to a study recently published in Nutrients.

Mia Stråvik, from Chalmers University of Technology in Gothenburg, Sweden, and colleagues compared the dietary intake of 508 pregnant and lactating women, validated the data with biomarkers of fatty acid proportions from breast milk and erythrocytes, and related these data to physician-diagnosed allergy in the offspring at 12 months of age.

The researchers found that an increased maternal intake of cow's milk during lactation was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. This association was confirmed with biomarkers (fatty acids: pentadecanoic acid and heptadecanoic acid) in the maternal blood and breast milk. There was a higher prevalence of atopic eczema seen at 12 months of age among mothers with a higher intake of fruit and berries during lactation.

"One hypothesis is that cow's milk contains something that activates the child's immune system and helps it to develop tolerance. This as-yet unknown cause could be found in the fat of the milk or in its protein content," a coauthor said in a statement. "But it could also be the case that the milk itself is neutral in relation to the immune system. Then it might be more simply a matter of a higher intake of milk fats leading to a relatively lower intake of polyunsaturated fats. This would help, because we believe high levels of polyunsaturated fat in a mother's diet can counteract the maturation of a child's immune system at an early age."

AHA: Mavacamten May Treat Hypertrophic Cardiomyopathy

Compared with placebo, mavacamten (Mava), a novel inhibitor of cardiac myosin, for 30 weeks leads to improvement in left ventricular (LV) hypertrophy and markers of left-sided filling pressures in patients with obstructive hypertrophic cardiomyopathy (oHCM), according to a study presented at the American Heart Association Scientific Sessions 2020, held virtually from Nov. 13 to 17.

Sheila M. Hegde, M.D., M.P.H., from Brigham and Women's Hospital in Boston, and colleagues examined the effect of Mava on focused measures of cardiac structure and function in oHCM in a double-blind, placebo-controlled phase 3 trial. Symptomatic oHCM patients were randomly assigned to either Mava or placebo for 30 weeks in a 1:1 ratio; 244 patients completed the study.

The researchers found that 30-week treatment with Mava led to significant reductions in left arterial volume index, lateral E/e', septal E/e'. and LV mass index compared with placebo. Significantly more patients treated with Mava than placebo achieved resolution of mitral valve systolic anterior motion and mitral regurgitation (80.9 versus 34.0 percent and 9.0 versus 0.0 percent, respectively).

"These findings reinforced and extended data from prior open label trials. Additional changes in measures of cardiac structure and function were also observed, including reduction in the size of the left atrium," Hedge said in a statement. "Together, these results reflect this medication's impact on the underlying pathophysiology of hypertrophic cardiomyopathy. A long-term extension trial is ongoing and will provide additional insight on the long-term impact on cardiac structure and function."

Several authors disclosed financial ties to pharmaceutical companies, including MyoKardia, which is developing mavacamten and funded the study.

FDA Approves Viltepso (viltolarsen) for the Treatment of Duchenne Muscular Dystrophy in Patients Amenable to Exon 53 Skipping Therapy

NS Pharma, Inc. announced  the U.S. Food & Drug Administration (FDA) has approved Viltepso (viltolarsen) injection for patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping therapy. Viltepso received an Accelerated Approval by the FDA based on an increase in dystrophin, a key protein for supporting muscle health. Since a lack of dystrophin is the underlying cause of DMD, increasing dystrophin as much and as early as possible is a key goal in the treatment of DMD. Viltepso is the first and only exon 53 skipping therapy to demonstrate an increase in dystrophin in children as young as four years old. The continued approval of Viltepso may be contingent on confirmation of a clinical benefit in a Phase 3 confirmatory trial.

DMD is caused by genetic mutations that prevent dystrophin production. Patients with DMD experience progressive and irreversible muscle loss with symptoms appearing as early as two years of age. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications.

The Viltepso New Drug Application (NDA) submission included results from a Phase 2, two-period study in patients aged four to less than 10 years of age conducted in North America (Study 1, N=16) and a multicenter, open-label study in boys five to less than 18 years of age conducted in Japan (Study 2, N=16).

In Study 1, of those patients who received the recommended dose of 80 mg/kg/wk (N=8), 100% of patients (8/8) showed an increase in dystrophin levels after treatment with Viltepso and 88% of patients (7/8) showed dystrophin levels of 3% or greater than normal. Overall, after 20-24 weeks of treatment a mean increase in dystrophin expression to nearly 6% of normal was observed with Viltepso (80 mg/kg/wk) versus 0.6% at baseline.

The most common side effects of Viltepso included upper respiratory tract infection, injection site reaction, cough and fever.

"For decades, neurologists who treat DMD have hoped for the discovery of therapies capable of significantly improving dystrophin production, and the magnitude of dystrophin increases observed with Viltepso are impressive," said study investigator Vamshi Rao, MD, Ann & Robert H. Lurie Children's Hospital of Chicago. "The approval of Viltepso is an exciting development for DMD patients amenable to exon 53 skipping therapy and may rapidly become a foundational treatment for these patients."

Patients receiving treatment with Viltepso have the option and flexibility to receive infusions at their home or at a hospital or treatment center. Viltepso is administered by a trained healthcare professional as an 80 mg per kg of body weight 60-minute weekly intravenous infusion.

NS Pharma will provide families, physicians and healthcare professionals dedicated and individualized resources every step of the way through the NS Support program. NS Pharma will be hosting a series of webinars on the comprehensive care coordination available through NS Support. Follow us on LinkedIn and Twitter for information and registration for upcoming webinars.

"On behalf of NS Pharma and Nippon Shinyaku, I would like to express our deepest gratitude to the families and physicians who participated in our clinical trials and made today's approval possible," said Tsugio Tanaka, President, NS Pharma, Inc. "We are proud to now offer an important new treatment option to help address the significant unmet needs caused by this devastating disease."

NS Pharma continues to study the safety and efficacy of Viltepso in the confirmatory Phase 3 RACER53 trial. This study was initiated in October 2019 and is currently enrolling. The purpose of this Phase 3 trial is to confirm the clinical findings that were submitted under the Accelerated Approval pathway.

https://www.rxlist.com/viltepso-drug.htm#description

FDA Approves Viltepso (viltolarsen) for the Treatment of Duchenne Muscular Dystrophy in Patients Amenable to Exon 53 Skipping Therapy

FDA Approves Evrysdi (risdiplam) for Treatment of Spinal Muscular Atrophy (SMA) in Adults and Children 2 Months and Older

Genentech, a member of the Roche Group, announced the U.S. Food and Drug Administration (FDA) approval of Evrysdi (risdiplam) for treatment of spinal muscular atrophy (SMA) in adults and children 2 months of age and older. Evrysdi showed clinically-meaningful improvements in motor function across two clinical trials in people with varying ages and levels of disease severity, including Types 1, 2, and 3 SMA. Infants achieved the ability to sit without support for at least 5 seconds, a key motor milestone not normally seen in the natural course of the disease. Evrysdi also improved survival without permanent ventilation at 12 and 23 months, compared to natural history. A liquid medicine, Evrysdi is administered daily at home by mouth or feeding tube.

“Given the majority of people with SMA in the U.S. remain untreated, we believe Evrysdi, with its favorable clinical profile and oral administration, may offer meaningful benefits for many living with this rare neurological disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “The strength and resolve of the SMA community has continually inspired us as we developed this first-of-its-kind medicine for SMA, so today we celebrate our collective accomplishment together with them.”

Evrysdi is being studied in more than 450 people as part of a large and robust clinical trial program in SMA. The program includes infants aged 2 months to adults aged 60 with varying symptoms and motor function, such as people with scoliosis or joint contractures, and those previously treated for SMA with another medication. The approval is based on data from two clinical studies designed to represent a broad spectrum of people living with SMA: FIREFISH in symptomatic infants aged 2 to 7 months; and SUNFISH in children and adults aged 2 to 25 years. SUNFISH is the first and only placebo-controlled trial to include adults with Types 2 and 3 SMA.

In FIREFISH, 41% (7/17) of infants treated with the therapeutic dose achieved the ability to sit without support for at least 5 seconds as measured by the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Additionally, 90% (19/21) of infants were alive without permanent ventilation at 12 months of treatment and reached 15 months of age or older. As described in the natural history of untreated infantile-onset SMA, infants would not be expected to be able to sit independently, and only 25% would be expected to survive without permanent ventilation beyond 14 months of age. In SUNFISH, children and adults treated with Evrysdi experienced a clinically-meaningful and statistical-significant improvement in motor function at 12 months (1.55 point mean difference; p=0.0156) compared to placebo (1.36 points [95% CI: 0.61, 2.11]; -0.19 points [95% CI: -1.22, 0.84], respectively), as measured by a change from baseline in the Motor Function Measure-32 (MFM-32) total score.

Evrysdi demonstrated a favorable efficacy and safety profile, with the safety profile established across the FIREFISH and SUNFISH trials. The most common adverse reactions were fever, diarrhea, and rash in later-onset SMA. In infantile-onset SMA, the most common adverse events were similar and also included upper respiratory tract infection, pneumonia, constipation, and vomiting. There were no treatment-related safety findings leading to withdrawal from either study.

“Throughout their lives, many people with SMA may lose their ability to perform critical movements, which can impact the ability to independently participate in aspects of daily life and even be life altering,” said Kenneth Hobby, president of Cure SMA. “The approval of Evrysdi is an eagerly awaited milestone for our community. We appreciate Genentech’s commitment to reflecting the full scope of the real-world SMA population in their clinical trial program and developing a treatment that can be administered at home.”

Evrysdi is designed to treat SMA by increasing production of the survival of motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement. Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Evrysdi will be available in the United States within two weeks for direct delivery to patients’ homes through Accredo Health Group Inc., an Express Scripts specialty pharmacy.

Genentech is committed to helping patients access the medicines prescribed by their physician. For people with SMA, the MySMA Support program team is available to answer questions, provide product education and help families understand insurance coverage and navigate appropriate financial assistance options to start and stay on Evrysdi. Patients can call 1-833-EVRYSDI or visit http://www.Evrysdi.com or https://www.Genentech-Access.com to learn more.

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

FDA Approves Evrysdi (risdiplam) for Treatment of Spinal Muscular Atrophy (SMA) in Adults and Children 2 Months and Older