FDA Greenlights XOLREMDI Capsules from X4 Pharmaceuticals for WHIM Syndrome Treatment

X4 Pharmaceuticals has declared that the FDA has granted approval for XOLREMDI™ (mavorixafor) capsules to be utilized in individuals aged 12 and above who have WHIM syndrome (characterized by warts, hypogammaglobulinemia, infections, and myelokathexis). This approval aims to enhance the count of mature neutrophils and lymphocytes circulating in the bloodstream.

XOLREMDI, an inhibitor of the selective CXC chemokine receptor 4 (CXCR4), represents a breakthrough in treating WHIM syndrome, a rare disorder combining primary immunodeficiency and chronic neutropenia due to dysfunction in the CXCR4 pathway. Individuals with WHIM syndrome typically exhibit low levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), making them prone to frequent and severe infections. Mavorixafor, as granted Breakthrough Therapy Designation by the FDA for WHIM syndrome treatment, underwent Priority Review for its potential to significantly advance the treatment, diagnosis, or prevention of serious conditions.

“The approval of XOLREMDI marks a significant turning point not only for X4 Pharmaceuticals but also for the WHIM syndrome community,” stated Paula Ragan, Ph.D., who serves as President and Chief Executive Officer of X4 Pharmaceuticals. “We extend our heartfelt appreciation to those affected by WHIM syndrome, their families, the researchers involved in our clinical trials, U.S. regulatory authorities for their ongoing commitment to rare disease therapies, and our devoted team for bringing this innovative treatment to fruition.”

The FDA’s approval of XOLREMDI was grounded on findings from the pivotal Phase III clinical trial called 4WHIM. This trial was conducted globally and involved a randomized, double-blind, placebo-controlled study spanning 52 weeks, with multiple centers participating. It aimed to assess the effectiveness and safety of XOLREMDI in 31 individuals aged 12 years and older diagnosed with WHIM syndrome. The effectiveness of XOLREMDI was evaluated by improvements in absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC), and a decrease in infections. Results from the 4WHIM trial revealed that treatment with XOLREMDI led to a significant increase in the time spent with absolute neutrophil counts above a certain threshold (≥500 cells/microliter) compared to the placebo (p<0.0001). Additionally, there was a significant increase in the time spent with absolute lymphocyte counts above another threshold (≥1000 cells/microliter) compared to the placebo (p<0.0001).

The FDA’s authorization of XOLREMDI has granted X4 a Rare Pediatric Disease Priority Review Voucher, which can either accelerate the review process for a future application or be traded to another pharmaceutical company.

ONO Finalizes Deal to Acquire Deciphera Pharmaceuticals

ONO Pharmaceutical, Co., Ltd., and Deciphera Pharmaceuticals, Inc. have announced that they reached a definitive agreement on April 29, 2024, whereby ONO will purchase all outstanding shares of Deciphera common stock at a price of US $25.60 per share in cash. This acquisition will be carried out through a tender offer, followed by a merger of a wholly owned subsidiary of ONO with Deciphera, with Deciphera continuing to operate as a wholly owned subsidiary of ONO. The total value of the acquisition stands at around US $2.4 billion, based on an estimated 94.7 million outstanding shares of Deciphera common stock on a fully diluted basis. The purchase price includes a premium of 74.7% over Deciphera’s closing share price of US $14.65 on April 26, 2024, and a premium of 68.8% over Deciphera’s 30 trading day volume-weighted average price as of April 26, 2024. The acquisition has received unanimous approval from the Boards of Directors of both companies.

Gyo Sagara, ONO’s Representative Director, Chairman of the Board, and CEO, expressed that the acquisition of Deciphera is anticipated to broaden ONO’s oncology offerings, expedite its business expansion in the United States and Europe, and enhance its research on kinase drugs. He noted the alignment between Deciphera’s mission of combating cancer and ONO’s commitment to battling disease and alleviating pain. Sagara emphasized ONO’s respect for Deciphera’s innovative culture and their joint efforts to foster growth for both companies.

ONO’s acquisition will broaden its oncology portfolio, driving revenue growth in the short term with the inclusion of QINLOCK® and potentially vimseltinib. Additionally, acquiring Deciphera’s commercial operations in the US and Europe will enhance ONO’s global market reach. Utilizing Deciphera’s expertise in drug discovery, ONO aims to expedite its oncology research and development efforts.

CHMP Recommends Full Approval for SIRTURO by Johnson & Johnson for Treating Multidrug-Resistant Tuberculosis

Johnson & Johnson has announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of a Type II variation for SIRTURO® (bedaquiline) and the transition of its Conditional Marketing Authorization to a standard Marketing Authorization. SIRTURO® is presently used as part of suitable combination therapy for pulmonary multidrug-resistant tuberculosis (MDR TB) in adult and pediatric patients aged 5 to under 18 years and weighing at least 15 kg, when a viable treatment regimen cannot be formulated due to resistance or tolerability issues. The approved usage may vary by country. The company’s ongoing support for bedaquiline underscores its enduring dedication to patients grappling with MDR-TB.

The CHMP’s favorable recommendation stems from findings in the Phase III STREAM Stage 2 trial, the inaugural extensive, randomized, multinational clinical examination assessing the effectiveness and safety of a fully oral regimen including bedaquiline for MDR-TB treatment. Outcomes exhibited that such regimens markedly outperformed alternative therapies, affirming the favorable risk-to-benefit profile of bedaquiline treatment, as documented in The Lancet in November 2022.

SIRTURO® received first accelerated approval from the FDA in December 2012 and conditional approval from the EMA in March 2014 after favorable Phase II study results. Alongside a Type II variation filed with EMA, a supplemental New Drug Application was presented to the FDA in August 2023 to facilitate the shift to full approval in the US. This application is presently undergoing review.

BeiGene’s Tislelizumab Secures European Commission Approval for Non-Small Cell Lung Cancer Therapy 

BeiGene, Ltd. has disclosed that the European Commission (EC) has granted approval for tislelizumab as a therapy for non-small cell lung cancer (NSCLC) in three different scenarios, encompassing both initial and subsequent treatment lines.

Mark Lanasa, M.D., Ph.D., Chief Medical Officer for Solid Tumors at BeiGene, emphasized the pivotal role of tislelizumab in BeiGene’s portfolio for treating solid tumors. He highlighted its efficacy across various tumor types, including NSCLC, where there’s a significant gap in available treatments at all disease stages. Lanasa celebrated the recent European Commission (EC) authorization of tislelizumab for NSCLC, adding to its prior approval for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) in the EU. He noted that the U.S. FDA also recently approved its second-line use in ESCC, demonstrating progress towards their goal of making this innovative therapy accessible to more patients worldwide.

The approved indications for tislelizumab are:

  • In conjunction with carboplatin and either paclitaxel or nab-paclitaxel, tislelizumab is indicated as the initial therapy for adult patients with squamous NSCLC who have locally advanced disease and are not eligible for surgical resection or platinum-based chemoradiation, or those with metastatic NSCLC.
  • In combination with pemetrexed and platinum-containing chemotherapy, tislelizumab is recommended as the first-line treatment for adult patients with non-squamous NSCLC whose tumors exhibit PD-L1 expression on ≥50% of tumor cells, lack EGFR or ALK positive mutations, and are ineligible for surgical resection or platinum-based chemoradiation, or have metastatic NSCLC.
  • Tislelizumab is also approved as a standalone therapy for adult patients with locally advanced or metastatic NSCLC following prior platinum-based treatment. Patients with EGFR mutant or ALK-positive NSCLC should have received targeted therapies before considering tislelizumab.

Tislelizumab gained approval for its NSCLC applications as TIZVENI®. BeiGene intends to merge these NSCLC applications with the second-line ESCC application, marketed as TEVIMBRA®, slated for release in select EU nations in 2024. TEVIMBRA has obtained approval in both the US and EU for advanced or metastatic ESCC following prior chemotherapy. Additionally, it is undergoing assessment by the European Medicines Agency and the FDA for potential approval as a primary treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC, as well as for primary treatment of gastric or gastroesophageal junction cancers.

Primary Endpoint Achieved in Sanofi’s Rilzabrutinib LUNA 3 Phase III Trial for Immune Thrombocytopenia

The LUNA 3 phase III trial yielded encouraging findings, demonstrating that administering rilzabrutinib orally at a dose of 400 mg twice daily effectively met its primary objective of sustaining platelet response in adult patients grappling with persistent or chronic immune thrombocytopenia (ITP). The safety profile of rilzabrutinib remained consistent with prior study reports.

The study successfully achieved its primary endpoint by showcasing a notably higher rate of durable platelet response among patients treated with rilzabrutinib compared to those on a placebo. This significant outcome, both clinically and statistically, was observed particularly in individuals with primary ITP who had not responded to previous treatments. Notably, participants in the study had undergone a median of four prior ITP therapies and started with a median baseline platelet count of 15,000/μL (the typical range for platelet counts being 150,000-450,000/μL). Additionally, positive results on secondary endpoints further highlight rilzabrutinib’s potential to offer substantial clinical advantages for individuals enduring persistent and chronic ITP.

The findings of this research further highlight the potential of rilzabrutinib as an innovative oral medication, capable of inhibiting BTK reversibly. It suggests significant benefits for individuals dealing with severe immune-mediated conditions such as ITP. These pivotal outcomes underscore our dedication and proficiency in rare blood disorders, showcasing our capability to develop a range of advanced small-molecule inhibitors. These inhibitors are designed to be more targeted and efficient, promising better efficacy and safety compared to current treatment options.

Houman Ashrafian (Executive Vice President, Head of Research and Development, Sanofi)

ITP, an acquired autoimmune blood disorder, is characterized by the destruction of platelets through autoantibodies and reduced platelet production, resulting in low platelet counts and a heightened risk of severe bleeding episodes, including intracranial hemorrhage. Additionally, individuals with ITP frequently suffer from fatigue and cognitive dysfunction, significantly impacting their quality of life. Rilzabrutinib offers a promising solution with its dual action targeting the production of harmful autoantibodies and the reduction of macrophage-mediated platelet destruction, potentially addressing various complications associated with ITP.