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FDA Grants Breakthrough Therapy Designations to Trastuzumab Deruxtecan for HER2+ Solid Tumors, Including mCRC
ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been granted two additional Breakthrough Therapy Designations (BTDs) in the United States for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, as well as for the treatment of patients with HER2 positive (IHC 3+) metastatic colorectal cancer who have received two or more prior regimens.
Daiichi Sankyo and AstraZeneca are working together to develop and commercialize ENHERTU, a precisely tailored HER2-directed antibody-drug conjugate (ADC). HER2 overexpression has been seen in 1% to 28% of metastatic solid tumors and up to 5% of colorectal cancer patients. There is an unmet need for effective medicines for various tumor forms, especially for patients who have progressed or are resistant to standard-of-care regimens.
The FDA approved the BTD for the treatment of metastatic HER2-positive solid tumors based on the findings of the ongoing DESTINY-PanTumor02 phase II trial, as well as data from other trials in the ENHERTU clinical research program. The findings of an interim study of DESTINY-PanTumor02 were presented as a late-breaking oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in previously treated patients with HER2 expressing metastatic solid tumors such as biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and other tumors. The BTD for the treatment of HER2-positive metastatic colorectal cancer was based on the final results of the DESTINY-CRC01 phase 2 study, which were presented at the 2022 ASCO Gastrointestinal Cancers Symposium (ASCO GI), and the primary results of the DESTINY-CRC02 phase II trial, which were presented at the 2023 ASCO Annual Meeting.
“ENHERTU is the first HER2 directed therapy to show a potential benefit across a range of difficult-to-treat cancers, and these designations acknowledge the ongoing potential of this innovative medicine,” said Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo. “We remain committed to exploring additional opportunities for ENHERTU in these tumor types, with the goal of bringing this treatment to more patients as soon as possible.”
ENHERTU has seven BTDs, and its designation in HER2 expressing metastatic solid tumors is the first time ENHERTU has acquired this designation in a tumor-agnostic environment. ENHERTU had previously been approved for three breast cancer indications: HER2 low metastatic breast cancer, second-line HER2 positive metastatic breast cancer, and later-line HER2 positive metastatic breast cancer. ENHERTU received two further BTDs for HER2 (ERBB2) mutant metastatic non-small cell lung cancer (NSCLC) and HER2-positive metastatic gastric cancer.
FDA Grants Orphan Drug Designation to Bexmarilimab for AML
Faron Pharmaceuticals Ltd., a clinical-stage biopharmaceutical company focusing on cancer immunotherapies, announced that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to its wholly-owned asset bexmarilimab for the treatment of acute myeloid leukemia (AML).
“Receiving Orphan Drug Designation from the FDA signifies our continued progress and commitment to developing bexmarilimab as a potential treatment for AML,” stated Chief Medical Officer Dr. Marie-Louise Fjällskog. “The designation represents a milestone in our development journey, one that we believe, when combined with standard of care, will lead to better patient outcomes and improved quality of life.”
Bexmarilimab is currently being studied in the Phase I/II BEXMAB trial (NCT05428969) in combination with standard of care (SoC) for the treatment of aggressive hematological malignancies such as relapsed/refractory AML and myelodysplastic syndromes (MDS). Faron published updated, promising data from the Phase I section of the trial last month. Three of five patients in the 6 mg/kg bexmarilimab + azacitidine doublet cohort obtained objective responses, while eight (out of 15 patients) in all three doublet dose cohorts achieved objective responses, with one patient remaining on medication for 13 months.
The completion of dose escalation, readout of enrichment cohorts, and the start of the BEXMAB trial’s Phase II part are expected in Q4 2023.
Roche Seeks Early-Stage Lung Cancer Use For Alecensa
Roche intends to seek approval for the use of its Alecensa drug in early-stage ALK-positive non-small cell lung cancer (NSCLC), which could mark a significant advancement as the first targeted therapy for these patients. This decision follows the results of the phase 3 ALINA study, which demonstrated that Alecensa (alectinib), an ALK inhibitor, achieved a “clinically meaningful” improvement in disease-free survival (DFS) in this specific cancer type, a groundbreaking development in this therapeutic category according to Roche.
Roche’s Chief Medical Officer, Levi Garraway, commented, “If granted approval, Alecensa has the potential to treat cancer at an early stage, where treatment can enhance the chances of a cure.” The study included patients with stage IB to IIIA tumors who had undergone surgery for their condition.
Roche emphasizes that despite adjuvant chemotherapy, approximately half of NSCLC patients experience disease recurrence after surgery, creating a critical need for new treatments that can offer a better chance of a cure. Ongoing monitoring of the patients in the ALINA study aims to determine whether the observed DFS improvement also translates into increased overall survival, a secondary endpoint.
Alecensa has already received FDA approval as a first-line therapy for patients with advanced, metastatic ALK-positive NSCLC. Roche now plans to submit the ALINA study data to regulatory agencies in the US, Europe, and other regions with the goal of expanding its approved uses to include early-stage disease.
Approximately 5% of all NSCLC cases are characterized by ALK mutations, and currently, patients with advanced disease have several treatment options, including Alecensa, Takeda’s Alunbrig (brigatinib), Novartis’ Zykadia (ceritinib), Pfizer’s older therapy Xalkori (crizotinib), and follow-up therapy Lorbrena (lorlatinib). Expanding Alecensa’s label to include early-stage disease would give Roche a unique position without competition from its rivals, as there is currently no indication that other companies are testing their ALK inhibitors in early-stage patients.
ALK-positive NSCLC is often diagnosed in younger individuals with a light or non-smoking history, and despite adjuvant chemotherapy, about half of early-stage patients experience cancer recurrence following surgery. The ALINA study compared Alecensa to platinum-based chemotherapy in the post-surgery setting but did not investigate the potential benefits of combining the two treatments.
In the first half of the year, Alecensa generated CHF 758 million ($857 million) in revenue, a 10% increase, with Roche claiming a leading position in all markets for the drug in advanced ALK-positive NSCLC.
Ergomed Aims To Go Private Via £703m Permira Takeover
Ergomed, the UK biopharma services company, is set to become a privately held entity as it undergoes a takeover by a subsidiary of the investment group Permira, which values the company at approximately £703 million ($888 million). Following the announcement, shares in Ergomed, which is listed on the London Stock Exchange, surged by over 25% to reach 1,332p, just slightly below Permira’s offer of 1,350p per share through its Eden AcquisitionCo.
Permira is also presenting an alternative to the cash offer, consisting of a smaller cash amount (451p) along with unlisted securities.
Ergomed’s board has endorsed the deal, marking a significant development nearly a decade after the company’s initial listing on the London exchange. The company has experienced years of growth through acquisitions, most notably its £26 million acquisition of the regulatory affairs consultancy ADAMAS last year. This expansion contributed to a 23% increase in revenues, totaling £145 million, for Ergomed last year. Analysts at Edison have even projected that the company could potentially reach revenues of £390 million by the end of the decade.
Ergomed traditionally followed a dual business strategy, serving as both a contract research organization (CRO) providing drug development and pharmacovigilance (PV) services to other drug developers for a fee and as a co-development partner for certain projects, sharing costs with other drug developers. However, the co-development aspect of the business was discontinued in 2018, with Ergomed focusing solely on the more profitable CRO and PV services. On the contract research side, Ergomed specializes in oncology and rare diseases, both of which have shown resilience in the face of recent declines in biotech funding.
Permira’s decision to acquire Ergomed stems from the company’s status as a “differentiated platform” in the pharmaceutical outsourcing sector, operating in markets experiencing growth due to increasing complexity, regulatory demands, and outsourcing rates. The private equity group has pledged to support Ergomed’s next phase of growth, providing investments in technology and commercial capabilities, and potentially engaging in “transformational” mergers and acquisitions (M&A).
Ergomed’s founder and executive chairman, Miroslav Reljanović, expressed optimism about the acquisition, stating that it offers a favorable opportunity for Ergomed shareholders to realize value at an attractive valuation while enabling Ergomed to effectively pursue its ambitious growth strategy.
Tagraxofusp Receives Orphan Drug Designation in Japan for BPCDN
On August 30, 2023, The Menarini Group (referred to as “Menarini”) and Stemline Therapeutics, Inc. (“Stemline”), a wholly-owned subsidiary of the Menarini Group, made an announcement stating that Nippon Shinyaku Co., Ltd. (Nippon Shinyaku), Stemline’s collaborator for development in Japan, has been granted Orphan Drug Designation by the Japanese Ministry of Health, Labor and Welfare (MHLW) for tagraxofusp for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). Stemline’s ELZONRIS® (tagraxofusp) represents the sole authorized treatment for BPDCN patients, earning the distinction of being the inaugural and exclusive CD123-targeted therapy approved in both the United States and Europe.
The MHLW’s decision to grant Orphan Drug Designation recognizes the potential positive impact tagraxofusp could have on BPDCN patients in Japan, a patient population that currently has limited treatment options. This achievement by our partner, Nippon Shinyaku, advances our commitment to bring transformative new therapeutic options to patients with difficult-to-treat cancers, and to deliver innovative medicines to people around the globe.Elcin Barker Ergun, CEO of the Menarini Group
In Japan, Nippon Shinyaku is overseeing the development of tagraxofusp and is actively progressing through a Phase 1/2 clinical trial. Stemline and Nippon Shinyaku initiated an exclusive licensing agreement in March 2021, covering the development and potential joint promotion of tagraxofusp in the Japanese market.
BPDCN, formerly known as blastic NK-cell lymphoma, is a highly aggressive hematologic cancer that often exhibits cutaneous symptoms and historically poor treatment outcomes. According to the Leukemia and Lymphoma Society, BPDCN constitutes less than 1% of all hematologic malignancies, resulting in an estimated 1,000 to 1,400 cases occurring annually in the US and Europe combined. BPDCN has been described in all age groups but is most common in adults. BPDCN represents 0.7 percent of primary cutaneous skin lymphomas. This malignancy typically manifests in the bone marrow and/or skin, with potential involvement in lymph nodes and internal organs. The plasmacytoid dendritic cell (pDC) precursor is the cell of origin for BPDCN. Diagnosis relies on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, in addition to other markers.
Abliva’s Lead Candidate KL1333 Receives FDA Fast Track Designation
On September 4, 2023, Abliva AB (Nasdaq Stockholm: ABLI) revealed that their primary candidate, KL1333, has been granted Fast Track status by the U.S. Food and Drug Administration (FDA), expediting its clinical advancement and progression toward market approval. At present, KL1333 is under assessment in the FALCON trial, which is a global Phase 2 study with potential registration implications for patients with mitochondrial disease. Dosage administration commenced in June of the current year, and an interim analysis is anticipated in mid-2024. Additionally, KL1333 has obtained orphan drug designation in both the USA and Europe.
The Fast Track designation is a quality stamp for our lead candidate and will facilitate our regulatory interactions in the U.S. This designation is one more important step forward as we prepare for a favorable interim analysis on the path towards bringing a new therapy to patients in this area of extremely high unmet medical need.Ellen Donnelly, CEO
KL1333 is in development as a potential treatment for a subgroup of adults affected by primary mitochondrial diseases, characterized by multiple debilitating symptoms such as chronic fatigue and myopathy. These conditions encompass diagnoses like MELAS-MIDD, KSS-CPEO spectrum disorders, and MERRF syndrome. KL1333 is a potent regulator of cellular NAD⁺ and NADH levels, pivotal co-enzymes in cellular energy metabolism. In a Phase 1a/b study involving mitochondrial disease patients, those administered with KL1333 demonstrated notable enhancements in fatigue symptoms and functional abilities.
Primary mitochondrial disease, also known as mitochondrial disorder or mitochondrial disease, refers to a group of rare genetic disorders that affect the mitochondria, the tiny structures within cells responsible for producing energy. These diseases result from mutations in either the nuclear DNA or the mitochondrial DNA, which can impair the function of the mitochondria. Approximately 125 individuals per million are estimated to suffer from primary mitochondrial diseases, typically emerging in early childhood and resulting in severe symptoms encompassing mental impairment, fatigue, muscle weakness, heart issues including failure and rhythm irregularities, diabetes, movement disorders, stroke-like episodes, and epileptic seizures. Diagnosis of primary mitochondrial disease often involves genetic testing and clinical evaluation by specialists. Treatment options are typically supportive and may include therapies to manage specific symptoms, such as physical therapy, speech therapy, or medications. There is ongoing research into potential treatments for mitochondrial diseases, but there is currently no cure for most of these conditions. Similarly, companies like Abliva among others are actively working to develop novel therapies to improve the treatment outcomes.