bluebird bio, Inc.

Sen. Tim Scott (R-SC) and Rep. Danny Davis (D-IL) are questioning the FDA’s “narrow” interpretation of “active ingredient” when it comes to awarding the potentially lucrative priority review vouchers. The letter , dated last Thursday and addressed to FDA Commissioner Rob Califf, focuses on the two FDA approvals of sickle cell gene therapies in late 2023. It explains how FDA’s recent administration of the PRV program — granting a PRV to one of the sickle cell gene therapies but not the other — “may not be fulfilling the program’s promise, original vision, and intent.” Scott and Davis question FDA on why it “made an initial decision to narrowly interpret the definition of ‘active ingredient’ in the PRV statute, resulting in the unexpected denial of at least one pediatric PRV.” But they also note that FDA “may be in the process of reconsidering its interpretation” so they want to make their thoughts clear. Bluebird bio had initially expected to win a PRV for its sickle cell gene therapy, approved in December 2023, and Novartis even drew up plans to purchase the PRV for $103 million. Ultimately, the FDA did not grant the PRV to bluebird, but Vertex Pharmaceuticals won a PRV for its gene therapy for sickle cell, approved on the same day as bluebird’s. A spokesperson told Endpoints News, “We believe that both the science and the congressional intent of the Rare Pediatric Disease Priority Review Voucher Program clearly support the issuance of a PRV associated with the approval of LYFGENIA and have continued to pursue a resolution with the FDA.” The FDA previously said that Lyfgenia contains the same active ingredient as bluebird’s gene therapy Zynteglo, approved for beta thalassemia. Scott and Davis explain how Congress did not define the term “active ingredient” in the law governing PRVs, but sought to prevent potential manufacturers from receiving PRVs for “simply making small tweaks to old drugs.” “The development of these complex gene therapies to treat an entirely new disease affecting thousands of patients can hardly be considered a ‘small tweak’ to an ‘old drug,'” the letter says, noting that Congress did not specify how FDA should determine if two active ingredients in an ex vivo gene therapy are the same or different. Scott and Davis add that FDA’s decision to interpret the law “in a narrower way than the statute requires – and one that flies directly against Congressional intent” risks disrupting “this delicate ecosystem, jeopardizing not only the availability of SCD treatments today, but also investments in complex and life-saving innovation for the future.” Editor’s note: Article updated with bluebird bio comment.

If Editas Medicine’s CRISPR gene-editing therapy for rare blood diseases reaches the market, it will be in the hands of a different company. The biotech on Tuesday announced plans to partner or out-license that clinical-stage ex vivo therapy, choosing instead to focus its resources on in vivo R&D that now has preclinical proof-of-concept data. The in vivo therapy, renizgamglogene autogedtemcel (reni-cel), has reached late-stage clinical development for severe sickle cell disease. Reni-cel is also in early-stage development for transfusion-dependent beta thalassemia. Patients who have these rare blood disorders already have ex vivo gene-editing treatment options. Last winter Vertex Pharmaceuticals’ Casgevy landed FDA approvals for sickle cell disease and beta thalassemia. Bluebird Bio’s last winter received FDA approval for Lygenia for sickle cell disease. A different Bluebird gene-editing therapy named Zynteglo won FDA approval in 2022 for beta thalassemia. Editas’s reni-cel would be third to market, but the Cambridge, Massachusetts-based company has said it could be best in the class of ex vivo therapies, made by editing a patient’s hematopoietic stem cells in a lab and infusing those cells back into the patient. These modified cells are intended to correct the anemia caused by these blood disorders and increase levels of fetal hemoglobin. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Dosing is continuing in reni-cel’s pivotal sickle cell study with 28 adult patients dosed to date; dosing is being scheduled for adolescent patients. Editas said data will be presented during the upcoming American Society of Hematology meeting in December. The beta thalassemia study is on track to present clinical data by the end of this year. Speaking during a Tuesday webcast, Editas CEO Gilmore O’Neill said the company is mindful of the financial cost that comes with commercializing an ex vivo autologous therapy. Placing reni-cel in the hands of another company would allow Editas to substantially reduce its 2025 spending. “We have previously said that we would be open to partnering reni-cel, but now, with the progress we’re making on in vivo editing, we are actively undertaking a process to partner or out-license reni-cel to most effectively drive it to commercialization while allowing us to apply our full attention and capital to in vivo medicines,” O’Neill said. “The in vivo data we are sharing today makes us even more confident in this decision.” The data that has Editas excited show proof of concept for its in vivo editing approach in mouse models for both sickle cell disease and beta thalassemia. Specifically, the company reported its in vivo therapy enabled an editing level of 29% in hematopoietic stem cells after a single dose. This treatment led to fetal hemoglobin induction (HbF), indicated by the presence of HbF-expressing human red blood cells populating in the host by one month. O’Neill said this level of in vivo editing in mice after a single dose is “highly competitive” compared to data in the public domain for the development of an in vivo medicine for sickle cell disease and beta thalassemia. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum In a note sent to investors, Leerink Partners analyst Mani Foroohar said the decision to seek an external partner for reni-cel makes sense given the cost of commercializing autologous ex vivo therapies. The near-term focus for Editas shares is the additional reni-cel data and the extent to which the company can show differentiation for the therapy to drive business development interest in this program. Editas said it has engaged investment bank Moelis & Company to lead the global process to partner or out-license reni-cel. Meanwhile, the company has secured non-dilutive financing to support its in vivo gene-editing focus. Earlier this month, Editas sold to DRI Healthcare Trust certain future license fees and payments owed under a Vertex Pharmaceuticals’ licensing agreement for Cas9 gene-editing technology. The DRI deal paid Editas $57 million up front. Editas reported its cash position as of the end of the third quarter of this year was about $265 million; or about $320 million including the DRI payment. O’Neill said the company has enough capital to fund operations into 2026. Public domain image by Flickr user NIH Image Gallery

Pfizer has announced an important decision to voluntarily withdraw all approved OXBRYTA® (voxelotor) lots for the treatment of sickle cell anemia (SCD) and to suspend clinical trials of voxelotor worldwide and its expanded access program. This move follows a review of recent clinical data showing that the overall benefit-risk ratio of OXBRYTA in the treatment of sickle-cell anemia no longer supports its continued use in the market. Specifically, the drug does not effectively manage complications and reduce the risk of death, and may increase the risk of serious adverse events such as vascular occlusive crises. Looking back, Pfizer paid as much as $5.4 billion to acquire this product, which has been successfully launched, and has high hopes for it. However, the rapid delisting of OXBRYTA has undoubtedly dealt a heavy blow to Pfizer's presence in this area, clouding the prospects for its sickle cell anemia treatment. Pfizer's investment in sickle cell anemia is based on the broad market demand for the disease. Although the incidence is low in developed countries, around 4.5 million people worldwide are affected by the disease, and more than 45 million carry the sickle cell gene. This large patient population provides Pfizer with significant market potential. As a result, Pfizer started laying out several years ago and acquired Global Blood Therapeutics (GBT) in 2022 for $5.4 billion, with OXBRYTA as one of its core products. However, although OXBRYTA inhibits sickle hemoglobin polymerization by enhancing hemoglobin's affinity for oxygen, thereby alleviating hemolytic anemia, its market performance has not met expectations. It is important to note that Pfizer's setback in sickle cell anemia is not an isolated event. The company also recently ended two late-stage clinical trials of another drug candidate, inclacumab, due to patient recruitment difficulties. This series of events shows that Pfizer's exploration of the sickle cell anemia market has not been easy. Still, Pfizer said it does not expect OXBRYTA's delisting decision to have a material impact on its financial outlook for 2024. This statement reflects Pfizer's steadiness and rationality in responding to market changes. From a larger perspective, Pfizer's failure in sickle cell anemia is also an inevitable result of increased competition in the industry. In recent years, with the rapid development of gene therapy and FDA approval of multiple gene therapies for sickle cell anemia, such as Vertex and CRISPR Therapeutics' Casgevy and Bluebird Bio's Lyfgenia, traditional medicines have faced unprecedented challenges. These gene therapies, which directly correct gene defects to achieve the goal of disease treatment or even a one-time cure, bring new hope to patients with blood diseases. Although gene therapy shows great potential in the field of medicine, its high cost remains a major challenge that cannot be ignored. For example, Vertex and CRISPR's Casgevy are priced at $2.2 million, while Bluebird Bio's Lyfgenia is priced at $3.1 million, sparking widespread social concern and deep concerns about its accessibility. In fact, most gene therapies cost more than $1 million, with some treatments costing as much as $3.5 million. Earlier this year, after an in-depth review by the Institute for Clinical and Economic Review (ICER), it was noted that a reasonable balance of cost-effectiveness could be achieved if Vertex and bluebird therapies were priced in the range of $1.35 million to $2.05 million. However, we should also face up to the whole new era created by cell gene therapy in the field of blood disease treatment, and its contribution and value cannot be ignored. Pfizer's recent failure in sickle-cell anemia once again highlights the complexity and uncertainty of the pharmaceutical industry. While Pfizer has long considered sickle-cell anemia products a strategic priority, its experimental drug rivipansel failed to perform as expected in the pivotal Phase III clinical study RESET, ultimately forcing the company to make a strategic change. In order to compensate for this deficiency, Pfizer chose to further improve its product line through mergers and acquisitions. Thanks to strong sales of COVID-19 vaccines, Pfizer now has ample financial firepower to fund its M&A strategy. However, "money for medicine" is not a long-term solution. As the dividend of COVID-19 gradually fades and the focus of the industry continues to shift, Pfizer has to face the reality of lower revenue expectations. Since the beginning of 2023, Pfizer shares have fallen by nearly half, from nearly $57 to $28.93. In response, Pfizer has launched a "cost reduction program" and plans to achieve $4 billion in savings by the end of 2024, $500 million less than previously expected. Company executives said the cost cuts will focus on research and development, but also involve optimizing sales and administrative functions. Entering the "post-COVID-19 era," Pfizer is experiencing unprecedented challenges and volatility. The decision to completely abandon the sickle cell anemia product line is not only a positive response to the current difficult situation, but also an important step in Pfizer's pursuit of greater certainty. However, in the face of the great pressure of competition from large manufacturers and the constantly changing industry environment, Pfizer's transformation road still has a long way to go. Whether it can find new growth points and achieve sustainable development in the future is still a problem worthy of attention.