Rare Diseases/Orphan Drugs

A drug that the FDA first approved more than a decade ago was recently approved for the first-line treatment of an aggressive blood cancer. One clinical trial showed that people on the agent experienced complete remission more than twice as often as those on a comparator therapy.

On March 19, the FDA gave accelerated approval to Takeda Pharmaceuticals U.S.A., Inc.’s Iclusig (ponatinib) in combination with chemotherapy for the treatment of adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The newest application had priority review and orphan drug designation, and its review used the Real-Time Oncology Review and the Assessment Aid.

Amylyx Pharmaceuticals, Inc. said on April 4 that it was voluntarily discontinuing the marketing authorization for Relyvrio (sodium phenylbutyrate and taurursodiol) in the U.S. and in Canada, where it is known as Albrioza. As part of a restructuring, the company also is laying off about 70% of its workforce. The FDA approved the agent for the treatment of amyotrophic lateral sclerosis (ALS) on Sept. 29, 2022, based on data from a Phase II trial involving 137 people. But on March 8, the company revealed that its Phase III PHOENIX trial did not meet the prespecified primary or secondary endpoints. Prior to the drug’s approval, the FDA’s Peripheral and Central Nervous System Drugs Advisory committee found that the study did not provide substantial evidence that the therapy was effective, but during a second meeting in September reversed course in favor of approval. At the time of Relyvrio’s approval, Amylyx co-founder and co-CEO Justin Klee declared that “if the PHOENIX trial is not successful, we will do what's right for patients, which includes taking the drug voluntarily off the market.” The company will not allow any new prescriptions for the drug, but it will transition current patients who wish to remain on treatment with Relyvrio to a free drug program. Amylyx will present topline data from the PHOENIX trial at the American Academy of Neurology Annual Meeting in Denver on April 16.

March 13: The FDA approved BeiGene, Ltd.’s Tevimbra (tislelizumab-jsgr) for the treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor. Recommended dosing for the PD-1 inhibitor is 200 mg via intravenous infusion once every three weeks. The initial dose is administered over 60 minutes; if it is tolerated, subsequent doses can be administered over 30 minutes. The drug will be available in the second half of 2024.

March 13: The FDA gave an additional indication to Mirum Pharmaceuticals, Inc.’s Livmarli (maralixibat) for the treatment of cholestatic pruritus in people at least 5 years old with progressive familial intrahepatic cholestasis (PFIC). The agency first approved the ileal bile acid transporter inhibitor on Sept. 29, 2021. The new indication has orphan drug designation, as well as breakthrough therapy designation for PFIC type 2. The starting dose for the newest use of the oral solution is 285 mcg/kg once daily in the morning, increasing to 285 mcg/kg twice daily, then 428 mcg/kg twice daily and then 570 mcg/kg twice daily. Drugs.com lists the price of 9.5 mg/mL for 30 milliliters as more than $56,239.

The FDA recently approved a first-in-class agent to treat a particularly deadly cancer. The therapy, Iovance Biotherapeutics, Inc.’s Amtagvi (lifileucel), signifies a promising new development in the treatment of solid tumors, which represent about 90% of all cancers in the U.S. While the drug comes with a price tag of more than $500,000, as well as additional costs, payers’ experience with chimeric antigen receptor T cells (CAR-T) therapies should be helpful in their coverage of the new agent, say industry sources.

On Feb. 16, the FDA gave accelerated approval to Amtagvi for the treatment of adults with unresectable or metastatic melanoma previously treated with a programmed death receptor-1 (PD-1) inhibitor and, if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor. The agency gave the therapy orphan drug, regenerative medicine advanced therapy, fast track and priority review designations.

Artificial intelligence (AI), drug shortages and cell and gene therapies are just a few of the areas on which the FDA is focusing during a major reorganization. Those were some of the topics that FDA Commissioner Robert Califf, M.D., discussed with Mike Tuffin, president and CEO of AHIP, at the insurer trade group’s 2024 Medicare, Medicaid, Duals & Commercial Markets Forum, held March 12 through 14 in Baltimore.

When asked his vision for the FDA in 2024 and beyond, Califf responded that 2024 priorities were different because it’s an election year, and the agency’s priorities are “tied to the administration that’s in place.”

Among the issues facing health care payers, paying for multimillion-dollar cell and gene therapies (CGTs) is one of the most pressing, as evidenced during AHIP’s 2024 Medicare, Medicaid, Duals & Commercial Markets Forum, held March 12 through 14 in Baltimore. While they were mentioned by multiple speakers throughout the three-day conference, speakers at one session focused on the topic said that while approaches such as short-term milestone-based contracts and risk pools are being used, no perfect solution has emerged yet.

Many CGTs are in the pipeline, impacting potentially millions of patients and prompting many questions around affordability and accessibility, stated Sean Dickson, senior vice president of pharmaceutical policy at AHIP, during the March 12 session, titled “Cell and Gene Therapies: Regulatory Updates and Coverage Policies.” “Oncology is where it will get really interesting,” and these agents will have the greatest impact on Medicare payers.

Feb. 9: The FDA approved Aurobindo Pharma Limited’s deflazacort for the treatment of Duchenne muscular dystrophy (DMD) in people at least 5 years old. The corticosteroid is the first generic of PTC Therapeutics, Inc.’s Emflaza that the agency has approved. It has approval as a tablet for all of Emflaza’s dosage strengths: 6 mg, 18 mg, 30 mg and 36 mg. Emflaza also is available as an oral suspension. That agent is approved for the treatment of DMD in people at least 2 years old; it has exclusivity for the treatment of people ages 2 to 5 years old until June 2026. The recommended daily dosing is 0.9 mg/kg. Drugs.com lists the price of 30 18 mg tablets of Emflaza as more than $9,706.

Feb. 9: The FDA approved Takeda Pharmaceuticals U.S.A., Inc.’s Eohilia (budesonide) for the treatment of people at least 11 years old with eosinophilic esophagitis. The corticosteroid is the first and only FDA-approved oral treatment for the indication. Recommended dosing is 2 mg twice daily for 12 weeks; the agent is available in 2 mg/10 mL single-dose stick packs. Its monthly wholesale acquisition cost is $1,875.

Coherus BioSciences, Inc. launched its Udenyca Onbody, an on-body injector (OBI) presentation of Udenyca (pegfilgrastim-cbqv), the company said Feb. 21. Approved Dec. 22, the OBI is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in people with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. Udenyca was first approved Nov. 2, 2018, and the leukocyte growth factor is one of six biosimilars of Amgen Inc.’s Neulasta (pegfilgrastim) that the agency has greenlighted. A health care provider must fill the OBI with the co-packaged syringe and apply it to the patient’s abdomen or back of the arm. About 27 hours after it is applied to the skin, the OBI will deliver a 6 mg/0.6 mL dose of Udenyca over about five minutes.

Catalyst Pharmaceuticals, Inc.’s Agamree (vamorolone) is now available in the U.S., the company said March 13. The FDA approved the first-in-class corticosteroid on Oct. 26 for the treatment of Duchenne muscular dystrophy in people at least 2 years old. The company is offering the comprehensive support program Catalyst Pathways Patient Assistance Program for Agamree for eligible patients. Drugs.com lists the price of 40 mg/mL oral suspension as more than $10,013.

CMS’s Cell and Gene Therapy Access Model’s first focus will be on therapies for sickle cell disease, the agency said Jan. 30. The administration unveiled the model almost one year ago as one of three new models for testing by CMS’s Innovation Center to lower the cost of drugs and increase access to new treatments. The model will implement outcomes-based agreements (OBAs) for cell and gene therapies to treat sickle cell disease beginning in 2025 “and may be expanded to other types of CGTs in the future.” The administration estimates that about half of people with sickle cell disease are enrolled in Medicaid, with health care services costing about $3 billion annually. Through the model, CMS will negotiate OBAs, and states can decide whether to enter into the arrangements. “CMS will negotiate financial and clinical outcome measures with drug manufacturers and then reconcile data, monitor results, and evaluate outcomes. The CGT Access Model will begin in January 2025, and states may choose to begin participation at a time of their choosing between January 2025 and January 2026.”

Jan. 12: The FDA broadened the label of Merck & Co., Inc.’s Keytruda (pembrolizumab) to include, in combination with chemoradiotherapy, the treatment of people with FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA cervical cancer. The agency initially approved the programmed death receptor-1 (PD-1) inhibitor on Sept. 4, 2014. The indication is the drug’s third in cervical cancer and 39th overall. The application was granted priority review. That review was conducted under Project Orbis in collaboration with the Australian Therapeutic Goods Administration and the Brazilian Health Regulatory Agency, and it used the Assessment Aid. Dosing is 200 mg every three weeks or 400 mg every six weeks via a 30-minute intravenous infusion. The agent’s price for every-three-weeks dosing is $11,115; for every-six-weeks dosing, it’s $22,230.