Daprodustat

An Akebia Therapeutics drug for a type of anemia has won FDA approval, a regulatory decision that comes nearly two years after the agency rejected the drug due to safety concerns. Safety remains a concern about the small molecule, vadadustat. The drug’s label carries a black box warning about an increased risk of death from a variety of cardiovascular complications. But the Akebia product, which will be branded as Vafseo, now introduces a new treatment option for the estimated 500,000 adults in the U.S who suffer from anemia due to chronic kidney disease (CKD). To use this drug, patients must have been receiving dialysis for at least three months. Anemia develops when there aren’t enough healthy red blood cells to carry oxygen to tissues in the body. It’s common in chronic kidney disease patients because their kidneys do not produce enough erythropoietin, a hormone that helps regulate red blood cell production. This anemia can be treated with erythropoietin-stimulating agents, engineered versions of the hormone administered as chronic injections. Akebia’s Vafseo offers more convenient oral dosing. This drug belongs to a class of drugs called hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors. By mimicking the effects of high altitude on the body, these drugs get the body to produce erythropoietin. When the FDA rejected this drug in 2022, it flagged cardiovascular risks and asked Akebia to run another clinical trial. Instead, the company resubmitted an application with additional post-marketing safety data from Japan, where the drug has been used since its approval there in 2020. Vafseo will compete against GSK’s Jesduvroq, which last year became the first FDA-approved oral medication for anemia caused by CKD. Jesduvroq is limited to patients who have been on dialysis for at least four months. Similar to Akebia’s drug, Jesduvroq’s label carries a black box warning for cardiovascular risks. Akebia said it will commercialize Vafseo in the U.S. with its established commercial team, which has renal experience and a relationship with CSL Vifor, the kidney disease-focused company that is the product of CSL Limited’s 2021 acquisition of Vifor Pharma. Here’s a recap of other recent regulatory news: —Winrevair, the pulmonary arterial hypertension (PAH) drug that was the centerpiece of an $11.3 billion Merck acquisition, won FDA approval. The PAH drugs already available treat symptoms. Winrevair is the first drug that addresses an underlying cause of this disorder affecting heart and lung function. —In other PAH news, the FDA approved Johnson & Johnson’s Opsynvi. This drug combines two older PAH drugs, macitentan and taladifil. Macitentan blocks the endothelin receptor while taladifil is a phosphodiesterase 5 inhibitor. Addressing both pathways requires patients to take multiple pills. Opsynvi is the first drug that combines both mechanisms in a single once-daily pill. —AstraZeneca’s drug Ultomiris added neuromyelitis optica spectrum disorder (NMOSD) as a new indication for the blockbuster drug. NMOSD is an autoimmune disease affecting the central nervous system, including the spine and optic nerves. Ultomiris blocks C5, a protein of the complement system, a part of the immune system. The drug has approvals for treating several other rare, complement system disorders. —Metabolic dysfunction-associated steatohepatitis (MASH), a fatty liver disease that affects as many as 7 million Americans, now has its first approved drug. The FDA gave the green light to Rezdiffra, a Madrigal Pharmaceuticals’ medication that posted clinical trial results showing it can reverse the liver scarring that is characteristic of the disorder. Madrigal’s once-daily pill carries an annual wholesale price of $47,400. —An Italfarmaco drug for Duchenne muscular dystrophy won FDA approval for treating all patients who have the inherited muscle-wasting disorder, regardless of the genetic variant driving their disease. Corticosteroids are a standard first-line therapy for Duchenne. The Italfarmaco drug, Duvyzat, is the first nonsteroidal therapy approved for the disease. —Orchard Therapeutics gene therapy Lenmeldy is now the first FDA-approved treatment for metachromatic leukodystrophy (MLD), a rare enzyme deficiency. Lenmeldy is made by modifying a patient’s hematopoietic stem cells to carry a functional gene that codes for the deficient enzyme. Orchard is now part of Japanese drugmaker Kyowa Kirin following a $387 million acquisition announced last year. —Regeneron Pharmaceuticals’ drug odronextamab was turned down by the FDA for two indications: follicular lymphoma and diffuse large B-cell lymphoma. According to Regeneron, the agency did not flag any safety, efficacy, or manufacturing issues for the bispecific antibody. The FDA told Regeneron it cannot resubmit applications until confirmatory studies are underway and completion timelines are agreed upon. Regeneron said it will share updates on enrollment and regulatory timelines later this year. The drug is still under regulatory review in Europe. —The FDA awarded full approval to AbbVie ovarian cancer drug Elahere. The antibody drug conjugate developed by ImmunoGen won accelerated approval in 2022. AbbVie acquired ImmunoGen last year in a $10.1 billion deal. —Invivyd antibody drug Pemgarda was granted emergency use authorization for prevention of Covid-19 in adults and adolescents with moderate-to-severe compromised immune systems. Other Covid-19 antibody drugs have had their authorizations revoked as they proved ineffective against new variants. Pemgarda comes from an Invivyd platform technology designed to address rapid viral evolution. —Idorsia Pharmaceuticals’ aprocitentan, brand name Tryviao, received FDA approval for treating hypertension when used in combination with other antihypertension drugs. The once-daily pill is designed to block the endothelin receptor. It’s the first approved high blood pressure drug with this mechanism of action. —Takeda Pharmaceutical drug Iclusig is now FDA approved for treating Philadelphia chromosome-positive acute lymphoblastic leukemia when used in combination with chemotherapy. The once-daily pill works by blocking enzymes associated with cancer growth. The accelerated approval adds to the list of indications for the drug, which is used to treat three types of leukemia. —The European Commission granted marketing authorization to Prevnar 20 for preventing pneumococcal disease in infants and children. The conjugate vaccine, which is designed to protect against the 20 circulating strains responsible for most pneumococcal infections, won European approval for adults in 2022. Prevnar 20 was first approved by the FDA for adults in 2021 and for children last year. —BeiGene cancer immunotherapy Tevimbra received a long-awaited FDA approval for treating adults with advanced esophageal squamous cell carcinoma. The FDA decision expected in 2022 was delayed by Covid-19. Though the drug received European Commission approval last year, BeiGene lost Novartis as a partner on the cancer therapy along the way. BeiGene said it expects Tevimbra, part of the class of drugs known as checkpoint inhibitors, will become available in the U.S. in the second half of this year. —Mirum Pharmaceuticals drug Livmarli landed FDA approval for treating pruritus, or severe itching, caused by the rare liver disease progressive familial intrahepatic cholestasis (PFIC). The approval cover patients age 5 and older. The company has also submitted an application seeking approval of a higher concentration formulation for treating younger PFIC patients. Livmarli was first approved by the FDA in 2021 as a treatment for pruritus caused by Alagille syndrome. Public domain image by Flickr user SciTechTrend

After a rocky two years following the FDA's initial rejection of Vafseo, Akebia can finally treat a portion of U.S. patients with anemia from chronic kidney disease. Akebia never lost confidence in its oral chronic kidney disease (CKD) anemia drug Vafseo, even after the FDA nixed its first approval bid two years ago with a complete response letter. Now, the company finally can celebrate a long-awaited U.S. approval. The FDA on Wednesday cleared Vafseo for patients with CKD-associated anemia who have been receiving dialysis for at least three months, kicking off a market showdown between Akebia and GSK. Thanks to a resubmission that included additional safety data from patients in Japan, where the drug has been marketed since 2020, the agency reconsidered its prior concern about potential liver toxicity. For the past two years, Akebia has been doing “everything we have to do” as a company to survive, CEO John Butler said in a recent interview with Fierce Pharma. That included laying off about half its staff and focusing on its lone commercial asset, CKD med Auryxia. The long road to approval The story of Vafseo, from Butler’s perspective, goes something like this: The FDA took issue with the potential for drug-induced liver injury, which Akebia disputed. In fact, the company felt so strongly that the agency made the wrong call that it initiated a formal dispute resolution process. Besides trial results, Akebia was armed with real-world data from Japan, where Mitsubishi Tanabe Pharma is handling commercialization of Vafseo. Japan specifically conducts “outstanding” post-marketing surveillance on its approved meds and hasn’t found any severe instances of drug-induced liver injury, bolstering the drugmaker’s confidence in its safety profile, according to Butler. Vafseo offers a different way to manage anemia than traditional erythropoiesis-stimulating agents, Butler explained. The drug, a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI), works through a unique technique of basically fooling the body into believing it's at a high altitude, effectively encouraging the bone marrow to produce more red blood cells. Vafseo would have been a first-in-class therapy if not for the two-year delay. Instead, that title went to GSK and its Jesduvroq, which was approved in February 2023. The rival also launched strictly in the dialysis-dependent patient population, much to GSK’s disappointment.   In July, GSK revealed its decision to not commercialize the med in Europe, despite winning support from the region’s drug evaluation committee the previous month. The company snatched back its application in Europe and opted to not seek approval in other countries based on the shrunken market opportunity that came without the non-dialysis population. Still, Jesduvroq’s presence in the U.S. market requires Akebia to adapt its original launch strategy, Butler acknowledged. A turnaround from hard times  The FDA nod promises to be “transformational" for the company, the CEO said. After two years of scraping by, Akebia can finally dip its toes in the sizable market for CKD anemia. However, unlike the drug's broad label in Japan, Akebia won't be able to reach the non-dialysis population—at least for now.  Beyond Vafseo, Akebia also looks to build on its pipeline, which already includes two preclinical compounds for acute kidney injury and blindness in newborn babies, or retinopathy of prematurity. All of that work will be done with a markedly smaller workforce than Akebia once had. Shortly after the original FDA rejection, the company had to cut about $60 million to $65 million in annual costs by letting go of 200 staffers, or 42% of its prior headcount. Following the job cuts, the FDA dispute resolution process began in October of 2022 and finally resulted in “a path forward” last May. “You know, you build culture for the hard times, and these were hard times, but people persevered and the light is very bright at the end of the tunnel,” Butler said. Since 2017, CSL Vifor has held the U.S. license to sell the med to Fresenius Medical Care dialysis centers nationwide. That $50 million deal was expanded in 2022 shortly before the FDA’s first decision, allowing Vifor to market Vafseo to “certain third-party dialysis organizations" responsible for treating 60% of U.S. dialysis patients. Akebia looks to launch Vafseo with the intention to “become a new oral standard of care” for dialysis patients, the company noted in its press release. Today, most patients are currently treated with standard injectable erythropoiesis-stimulating agents. With the U.S. nod, the med is now approved in 37 countries.