Crizanlizumab-TMCA

The withdrawal decision was prompted by clinical data indicating that the overall benefit of Oxbryta “no longer outweighs the risk” in its target patient population, the company said in a public release ​. Specifically, the trials outline an “imbalance” in vaso-occlusive crises and fatal events that the company will assess further. The move to stop clinical trials of the drug will last while Pfizer further reviews the available data and investigates the findings. Sickle cell disease is a genetic blood disorder where patients have a mutation in hemoglobin, a protein found in red blood cells. This leads the protein to clump together, causing cells to have a sickle shape that can block blood vessels and carry less oxygen, leading to acute pain and anemia. Oxbryta, whose generic name is voxelotor, is an oral small molecule drug that was first approved by the US Food and Drug Administration (FDA) for the treatment of sickle cell disease in 2019, with an EU approval granted in 2022. The drug is designed ​ to make hemoglobin better at carrying oxygen and less prone to clumping together, making red blood cells more functional. The treatment was previously developed by the U.S. firm Global Blood Therapeutics before the company was snapped up by Pfizer for $5.4 billion in 2022 ​, and bagged Pfizer $328 million in revenues in 2023 ​. The big pharma company has notified regulators about the data and doesn’t expect the event to impact its full-year 2024 financial guidance. Nevertheless, the company’s stock price on the New York Stock Exchange slumped by more than 1% at the news yesterday (Wednesday 25th September). googletag.cmd.push(function () { googletag.display('text-ad1'); }); Emphasizing Pfizer’s focus on patient safety, chief medical officer and head of worldwide medical and safety, Aida Habtezion, said in the company release that the Pfizer’s “primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options. We advise patients to contact their physicians to discuss alternative treatment while we continue to investigate the findings from our review of the data.” The global market for sickle cell disease was worth ​ $2.25 billion in 2022 and is expected to grow by 20.1% per year to $9.84 billion by 2030. The main players in the market have included Pfizer with Oxbryta, Novartis with the antibody Adakveo (crizanlizumab) and Generex Biotechnology’s Emmaus Medical with Endari (L-glutamine). In 2017, Endari became the first branded drug for sickle cell disease in decades when it was greenlit by the U.S. FDA. Another driver for the sickle cell disease market is gene therapy, with the first cell-based gene therapies – Casgevy by Vertex Pharmaceuticals and Lyfgenia by Bluebird Bio – approved by the U.S. FDA in late 2023 ​.

A BeiGene drug already used to treat several types of blood cancer now has an additional FDA approval as a treatment for follicular lymphoma. The regulatory decision makes the BeiGene drug the first in its class for treating this type of cancer. The FDA last Thursday approved zanubrutinib, brand name Brukinsa, for patients whose follicular lymphoma has not responded to two or more lines of therapy. BeiGene’s twice-daily capsule is administered alongside periodic infusions of obinutuzumab, brand name Gazyva, a targeted therapy from Roche that is a standard follicular lymphoma treatment. The new approval comes four months after European Commission approval of Brukinsa for follicular lymphoma. Follicular lymphoma is a slow-growing form of non-Hodgkin lymphoma, a cancer affecting white blood cells called lymphocytes. Brukinsa belongs to a class of therapies called BTK inhibitors. The small molecule drug is designed to block Bruton’s tyrosine kinase (BTK), an enzyme that drives cancer cell growth. The approval in follicular lymphoma is based on the results of a clinical trial that enrolled 217 adults and compared treatment with Brukinsa and Gazyva to treatment with Gazyva alone. The main goal was to measure the overall response rate and the duration of response. Results showed an overall response rate of 68% in the study drug arm compared to 46% in the control group. With a median follow-up of 19 months, the median duration of response was not reached in the Brukinsa/Gazyva arm, and was 14 months in the Gazyva group. Across the drug’s clinical trials, the most common adverse reactions included low levels of a type of white blood cell called a neutrophil, upper respiratory tract infections, bleeding, and muscle pain. Brukinsa won its first FDA approval in 2019 for the treatment of mantle cell lymphoma. Its other approved indications are Waldenstrom’s macroglobulinemia, marginal zone lymphoma, and chronic lymphocytic leukemia (CLL). The drug is BeiGene’s top product, accounting for $1.3 billion in revenue in 2023, a more than 128% increase over the product’s sales in 2022. In its annual report, BeiGene said Brukinsa’s U.S. sales growth in 2023 was driven by the product’s launch in CLL. Brukinsa is currently approved in 70 countries. With Brukinsa’s latest FDA nod, the BTK inhibitor joins a small group of therapies already available as third-line treatments for follicular lymphoma. The CAR T-therapies Kymriah from Novartis and Yescarta from Gilead Sciences are such treatment options. Another choice is Lunsumio, a bispecific T cell engager developed by Roche and approved by the FDA in 2022. The FDA nod for Brukinsa in follicular lymphoma is an accelerated approval that requires a post-marketing study to confirm the therapy’s efficacy. BeiGene said a Phase 3 trial already underway will serve as the confirmatory clinical trial for this indication. “This accelerated approval of Brukinsa represents an important advancement, offering the first and only BTK inhibitor treatment for follicular lymphoma patients in the U.S. who have either not responded to initial therapies or have experienced relapse,” Mehrdad Mobasher, BeiGene’s chief medical officer, hematology, said in a prepared statement. Here’s a recap of other recent regulatory news: —Blockbuster Novo Nordisk drug Wegovy, approved as a treatment for weight management, is expanding its label to include reducing cardiovascular risks in those who are obese or overweight. FDA approval of the additional indication is based on results from a clinical trial showing that patients who treated with Wegovy experienced a significantly lower rate of cardiovascular events compared to those who received a placebo. That study followed more than 17,000 participants for up to five years. —Eli Lilly Alzheimer’s disease drug donanemab won’t receive a first quarter 2024 regulatory decision as expected. The FDA wants to convene an advisory panel to discuss the safety and efficacy of the antibody drug, including the unique trial design that allowed patients to complete their course of treatment upon reaching a prespecified level of amyloid plaque clearance. The meeting date has not yet been set. Lilly said holding an advisory committee for donanemab is consistent with the review of Aduhelm and Leqembi, antibody drugs that previously won approvals in Alzheimer’s disease. —Sandoz received FDA approvals for two biosimilars that are interchangeable with the blockbuster Amgen products Prolia and Xgeva, antibody drugs that block a protein called RANKL to treat osteoporosis and bone problems in cancer patients. The new Sandoz drugs, Jubbonti and Wyost, are the first FDA-approved RANKL inhibitor biosimilars. —Partners Formosa Pharmaceuticals and Aimax Therapeutics received FDA approval for a new formulation of a topical steroid developed for treating inflammation and pain following eye surgery. The drug, clobetasol propionate ophthalmic suspension, is made with Formosa’s nanoparticle formulation technology. The Formosa drug will be commercialized in the U.S. by Eyenovia, a New York company that acquired U.S. rights to the steroid. A mid-year launch is planned. Eyenovia also said it also exploring development of this product, delivered with its Optejet dispenser device, as a potential treatment for dry eye disease. —The FDA approved Johnson & Johnson drug Rybrevant as a first-line treatment for non-small cell lung cancer that carries the rare EGFR exon 20 insertion mutation. The J&J antibody drug initially won accelerated approval in 2021. The new FDA decision converts Rybrevant’s status to full approval. It’s based on the results of a confirmatory Phase 3 study that showed a statistically significant improvement in progression-free survival. —EMD Serono, the healthcare business of German company Merck KGaA, also converted an accelerated approval to a traditional one. The FDA approved the company’s Tepmetko for treating adults with advanced non-small cell lung cancer that has MET exon 14 skipping alterations. Tepmetko received accelerated FDA approval in 2021. —The FDA turned down a Minerva Neurosciences application seeking approval of roluperidone as a treatment for symptoms of schizophrenia. The drug is designed to selectively block certain receptors involved in regulating brain functions, such as mood and anxiety. Among the deficiencies cited: The application included a statistical significance finding from only one clinical trial, which on its own is insufficient to provide substantial evidence of effectiveness, the agency told Minerva. The FDA asked Burlington, Massachusetts-based Minerva to submit data from at least one additional well-controlled clinical trial and also provide more data to show the drug’s safety and efficacy when co-administered with other antipsychotic medications. Minerva said it would request a meeting to discuss the FDA letter. —Allecra Therapeutics received FDA approval for Exblifep for treating complicated urinary tract infections in adults. The antibiotic is part of a class of drugs that work by inhibiting synthesis of a bacterium’s cell wall. With the approval, France and Germany-based Allecra receives five-year marketing exclusivity for the product under the Generating Antibiotic Incentives Now Act, which was enacted to incentivize anti-infective product R&D. Allecra said it is in discussions with potential U.S. commercialization partners for Exblifep. —Novartis is withdrawing Adakveo from the U.K. market after post-marketing testing failed to confirm the drug’s benefit. Adakveo was developed to treat vaso-occlusive crises, a complication of sickle cell disease. The exit from the U.K. market follows the withdrawal of the drug from the European Union last year. At that time, the company said it also planned to discuss the study results with the FDA. —The European Commission granted marketing authorization for Pfizer drug Velsipity as a treatment for moderately to severely active ulcerative colitis in patients 16 and older. The once-daily oral drug is a small molecule designed to selectively target and block three S1P receptors. European approval of Velsipity follows the drug’s FDA approval last October. —Iovance Biotherapeutics’ Amtagvi won the first FDA approval for a type of cell therapy called a tumor-infiltrating lymphocyte, or TIL. The regulatory decision also marks the first approval of a cell therapy for treating solid tumors. Amtavi’s approval specifically covers the treatment of advanced cases of melanoma. The one-time treatment carries a $515,000 wholesale price. —Xolair, an old Roche drug whose approved uses include treating asthma, received a new FDA approval for reducing allergic reactions in people who have food allergies. Xolair is an antibody that blocks immunoglobulin E, an antibody produced by the immune system in response to an allergen. The drug’s latest regulatory decision covers adults as well as children age 1 and older who have food allergies. Xolair’s is not an emergency treatment for allergic reactions to food. People who have food allergies should continue to avoid trigger foods. But Xolair reduces allergic reactions in instances of accidental exposure to a food allergen.