Disc Medicine Receives FDA Fast Track Designation for MWTX-003 for the Treatment of Polycythemia Vera

On Sept. 20, 2023, Disc Medicine, Inc. (NASDAQ: IRON) announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to MWTX-003 for the treatment of patients with Polycythemia Vera (PV).

MWTX-003, also known as DISC-3405, is an investigational, anti-TMPRSS6 (Transmembrane Serine Protease 6, also known as Matriptase-2) monoclonal antibody designed to increase hepcidin production and suppress serum iron, that Disc in-licensed from Mabwell Therapeutics in January 2023. Preclinical studies of MWTX-003 have demonstrated an increase in hepcidin production and suppression of serum iron levels in animal models of beta-thalassemia and Polycythemia Vera. The IND was accepted in November 2022 and Disc plans to initiate a Phase 1 study of MWTX-003 in healthy volunteers during the second half of 2023. Disc plans to develop MWTX-003 initially as a treatment for Polycythemia Vera as well as other hematologic conditions. MWTX-003 is an experimental substance and has not received approval for use as a treatment in any jurisdiction globally.

We are delighted to have received Fast Track designation for MWTX-003, which highlights the unmet need for PV patients and the potential of MWTX-003 in a disease where there are few treatment options. We believe MWTX-003 is uniquely positioned to address the needs of PV patients and are excited to initiate a Phase 1 trial in the coming months.

John Quisel, J.D., Ph.D., President and Chief Executive Officer of Disc.

Polycythemia Vera (PV) is a chronic and uncommon myeloproliferative disorder characterized by the abnormal overproduction of red blood cells. The excessive production of red blood cells leads to changes in blood viscosity, resulting in increased thickness and raising the likelihood of cardiovascular and thromboembolic events, such as heart attacks and strokes, for patients. As per DelveInsight, the total Polycythemia Vera prevalent cases in the 7MM was found to be 309,000 cases in 2022 and the number of cases are projected to increase in the upcoming years. The total prevalent cases of Polycythemia Vera in the United States were around 179,000 cases in 2022. 

Presently, the management of Polycythemia Vera typically encompasses two main approaches. One method involves phlebotomy, a procedure in which blood is physically withdrawn from the patient to reduce the volume of blood and decrease iron levels, ultimately curbing the excessive production of red blood cells. This approach serves to maintain hematocrit levels within a normal range and mitigate the risk of complications associated with increased blood thickness. Another therapeutic avenue involves the use of cytoreductive agents, which are medications designed to regulate the overproduction of blood cells in the bone marrow. These agents help in lowering the red blood cell count and mitigating the overall disease burden. Their application is particularly valuable for individuals who may not be suitable candidates for frequent phlebotomy or who require more comprehensive control of their condition. Globally, several major pharmaceutical and biotech giants, like Disc Medicine among others, are actively developing Polycythemia Vera therapies for better treatment outcomes. 

FDA Accepts Submission to Add PH-ILD to YUTREPIA Label

Liquidia Corporation announced that the U.S. Food and Drug Administration (FDA) has agreed to review the company’s modification to the preliminary approval of their new drug application (NDA) for YUTREPIA™ (treprostinil) inhalation powder. This amendment aims to include the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD) in the drug’s label. The FDA specified the resubmission type as Class II and set a Prescription Drug User Fee Act (PDUFA) goal date of January 24, 2024.

Dr. Rajeev Saggar, Chief Medical Officer of Liquidia, expressed satisfaction with the FDA’s acceptance of the submission for review, particularly noting the early PDUFA goal date before the March 2024 expiration of the new clinical investigation exclusivity granted to Tyvaso®. Dr. Saggar highlighted that if this amendment is approved, YUTREPIA would be indicated for treating both PH-ILD and pulmonary arterial hypertension (PAH).

The FDA initially granted tentative approval for YUTREPIA to address PAH in November 2021 and confirmed that including the PH-ILD indication would not necessitate new clinical studies. However, the launch of YUTREPIA for both indications is contingent upon successful resolution of the ongoing litigation with United Therapeutics and final FDA approval. Moreover, final FDA approval for the PH-ILD indication might be delayed until after the new clinical investigation exclusivity granted to Tyvaso expires on March 31, 2024.

FDA Issues CRL to BLA for On-Body Injector Presentation of Pegfilgrastim-cbqv

Coherus BioSciences, Inc. announced that the U.S. Food and Drug Administration (FDA) has issued a Comprehensive Response Letter (CRL) pertaining to the Biologics License Application (BLA) supplement for UDENYCA® ONBODY™, the on-body injector (OBI) presentation of UDENYCA® (pegfilgrastim-cbqv). This action was solely due to an ongoing assessment of inspection findings at a third-party filler. It’s important to note that the CRL did not flag any concerns regarding UDENYCA® ONBODY™’s clinical effectiveness or safety, trial design, labeling, drug substance manufacturing, or device design or manufacturing. Furthermore, the FDA did not request additional data or trials. Coherus remains committed to closely collaborating with the FDA and the third-party filler to expedite the availability of UDENYCA® ONBODY™ to cancer patients in need of pegfilgrastim treatment.

In addition, Coherus reported the successful completion of the FDA’s inspections for toripalimab. The FDA concluded clinical study site inspections at three clinical sites in China that enrolled subjects for the pivotal clinical trials supporting the toripalimab BLA for the treatment of metastatic or recurrent nasopharyngeal carcinoma (NPC) as the first-line or subsequent-line treatment. Only one site received an FDA Form 483, noting a single observation, which Coherus believes can be promptly addressed. Coherus maintains its expectation of potential approval for toripalimab by the end of 2023.

Dr. Theresa LaVallee, Coherus Chief Development Officer, expressed contentment with the completion of the FDA’s review for the OBI and toripalimab applications. She emphasized the intent to collaborate with the third-party filler to resolve the concerns and promptly resubmit the UDENYCA® ONBODY™ application. Additionally, having completed all necessary review components for the toripalimab BLA, Coherus will continue working closely with the FDA to introduce toripalimab, offering significant survival improvement compared to chemotherapy, to patients with NPC—an uncommon cancer with a significant unmet medical need lacking approved treatments in the U.S.

LEQEMBI Intravenous Infusion Approved for the Treatment of Alzheimer’s Disease in Japan

Eisai Co., Ltd. and Biogen Inc. announced that LEQEMBI® Intravenous Infusion (200 mg, 500mg, lecanemab) has been approved in Japan as a treatment for slowing the progression of mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). 

LEQEMBI is a humanized IgG1 monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of A. LEQEMBI is the first and only licensed medication that has been demonstrated to attenuate cognitive and functional decline while slowing disease progression by selectively binding to and removing the most toxic A aggregates (protofibrils) that contribute to neurotoxicity in AD. In Japan, a marketing permission application was filed, and it was selected for priority consideration in January 2023. Following the traditional approval in the United States in July 2023, Japan is the second country to issue approval.

LEQEMBI received approval based on Phase III data from the extensive Clarity AD clinical trial conducted by Eisai. The trial demonstrated LEQEMBI’s efficacy by meeting its primary endpoint and all key secondary endpoints with statistically significant results, thus confirming its clinical benefits. The primary endpoint assessed global cognitive and functional abilities using the Clinical Dementia Rating Sum of Boxes (CDR-SB). 

Today marks a significant milestone as LEQEMBI receives approval, becoming the first anti-amyloid Alzheimer’s disease treatment approved in Japan. This breakthrough treatment has shown promising results in slowing the progression of the disease and mitigating cognitive decline in the early and mild stages of dementia. Haruo Naito, Chief Executive Officer at Eisai, shared his thoughts on this historic moment, stating, ‘We believe this marks a turning point in the treatment of Alzheimer’s disease.

Eisai takes on the primary role in the global development and regulatory submissions for LEQEMBI, while both Eisai and Biogen collaborate in marketing and promoting the product. Eisai retains ultimate decision-making authority in this partnership. In Japan, Eisai and Biogen Japan will jointly promote LEQEMBI, with Eisai serving as the Marketing Authorization Holder.

Novartis’ Lutathera Shows Significant & Clinically Meaningful Improvement in First-line Advanced GEP-NETs’ Progression-free Survival

Novartis reported that the Phase III NETTER-2 trial, evaluating Lutathera, achieved its primary objective. The study showed that when used as a first-line treatment in combination with long-acting octreotide, Lutathera significantly increased progression-free survival (PFS) in patients with newly diagnosed somatostatin receptor (SSTR)-positive, Grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), compared to high-dose long-acting octreotide treatment alone. The safety profile of Lutathera remained consistent with previous findings, and no new safety concerns emerged.

NETs, or neuroendocrine tumors, are a type of cancer that originate in neuroendocrine cells found throughout the body. While they are generally considered slow-growing malignancies, some NETs exhibit rapid progression and have a poor prognosis. Often, patients are diagnosed at an advanced stage of the disease. Despite being classified as a rare or orphan disease, the incidence of NETs has surged by over 500% in the past three decades. Consequently, there is a pressing need for additional treatment options for patients newly diagnosed with inoperable or advanced NETs. 

The latest results from the NETTER-2 trial mark the second Phase III study demonstrating clinically significant outcomes for patients using Lutathera. The initial approval of Lutathera was based on the pivotal NETTER-1 trial, which exhibited a highly significant and clinically meaningful extension of progression-free survival (PFS) for patients treated with Lutathera in combination with long-acting octreotide when compared to high-dose (60 mg) long-acting octreotide, specifically for those with SSTR-positive, inoperable midgut neuroendocrine tumors (NETs) that were progressing despite standard treatment.

Lutathera’s positive outcomes are truly remarkable, highlighting the potential of radioligand therapy to significantly benefit newly diagnosed patients grappling with advanced GEP-NETs,” according to Jeff Legos, Executive Vice President and Global Head of Oncology Development at Novartis. “Our exploration of radioligand therapies in earlier stages of cancer treatment aligns with our broader, cooperative mission to precisely target cancer cells with innovative treatments for improved patient results.

The NETTER-2 study outcomes are scheduled for presentation at an upcoming medical conference, where we will also confer with regulatory agencies.

AbbVie Announces European Commission Approval of TEPKINLY® (epcoritamab) for Adults with Relapsed or Refractory Diffuse Large B-cell Lymphoma

On September 25, 2023, AbbVie (NYSE: ABBV) revealed that the European Commission (EC) has provided provisional marketing authorization for TEPKINLY® (epcoritamab) as a standalone treatment for adult patients with relapsed or have refractory (R/R) diffuse large B-cell lymphoma (DLBCL) following two or more rounds of systemic therapy. TEPKINLY marks a significant milestone as it becomes the inaugural subcutaneous T-cell engaging bispecific antibody to receive approval for addressing this specific patient group in the European Union (EU), including Liechtenstein, Norway, and Iceland.

TEPKINLY is a collaborative effort between AbbVie and Genmab in the field of oncology. In the United States and Japan, both companies will jointly handle commercial responsibilities, while AbbVie will take charge of its global commercialization. AbbVie remains committed to submitting regulatory applications for epcoritamab in various international markets throughout the year.

This provisional authorization is underpinned by findings from the pivotal EPCORE™ NHL-1 Phase 1/2 open-label, multi-cohort, multi-center, single-arm trial, which assessed the initial effectiveness and safety of TEPKINLY in patients with relapsed or refractory large B-cell lymphoma (LBCL), including the diffuse large B-cell lymphoma (DLBCL) subtype. Within this investigation, DLBCL patients who received TEPKINLY (N=139) achieved an overall response rate of 62 percent and a complete response rate of 39 percent. Furthermore, the median duration of response extended to 15.5 months (with a range of 9.7 to not reached).

The trial findings indicated that TEPKINLY exhibited a well-tolerated safety profile in the group of patients with LBCL, encompassing those with DLBCL (N=167). The most frequently reported adverse events (occurring in ≥ 20 percent of patients) included cytokine release syndrome, fatigue, neutropenia, injection site reactions, musculoskeletal pain, abdominal discomfort, fever, nausea, and diarrhea.

The European Commission approval of epcoritamab represents a significant milestone in our aspiration with Genmab to develop a potential core therapy for patients with B-cell malignancies, like DLBCL. With this milestone achievement, TEPKINLY is now the second approved cancer treatment in the EU from our oncology portfolio and AbbVie’s third blood cancer medicine across the world. We remain committed to developing new innovative medicines that help improve the lives of people with hematological cancers.

Roopal Thakkar, senior vice president, development and regulatory affairs, chief medical officer, AbbVie.

Relapsed or refractory DLBCL is an aggressive cancer and patients can face a difficult and emotional treatment journey. At this point in the journey, a patient may have had multiple lines of therapy and will already have experienced relapse. This European Commission approval represents an important moment for the DLBCL patient community and brings with it a potential opportunity for effective disease management for a condition with limited available treatment options.

Anna Sureda, M.D., Ph.D., Head of the clinical hematology department, Institut Català d’Oncologia – L’Hospitalet, Barcelona, Spain

DLBCL stands as the prevailing form of B-cell non-Hodgkin’s lymphoma on a global scale. The total diffuse large B-cell lymphoma (DLBCL) incident population in the 7MM was 73,000+ cases in 2021. The total incident population of DLBCL in the United States is 29,000+ in 2021. The United States contributed to the largest incident population of DLBCL, accounting for ~ 41% of the 7MM in 2021. Despite the existence of chemoimmunotherapy approaches for disease management, patients encounter a constrained array of treatment choices, with only a handful of readily accessible pharmaceutical solutions, particularly for those individuals whose condition has relapsed or developed resistance to previous therapies. Globally, several major pharma and biotech giants are actively working in the diffuse large B-cell lymphoma (DLBCL) therapeutics market to improve the treatment outlook.