FDA Grants Orphan Drug Designation to AUM302 for Neuroblastoma

A global clinical-stage biotech company, AUM Biosciences, focused on discovering and developing precision oncology therapeutics, declared that the U.S. FDA has permitted Orphan Drug Designation for AUM302. For the treatment of neuroblastoma, AUM302 is a potential first-in-class oral kinase inhibitor that not only targets PI3K but also important resistance mechanisms like PIM and mTOR.

Preclinical studies of AUM302 have showed that complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition can improve clinical outcomes in children having high-risk of neuroblastoma and inhibit cancer cell growth, and prevent resistance emergence.

Orphan Drug Designation status is granted by the FDA’s Office of Orphan Products Development to drug and biologic drugs that are planned for the treatment, diagnosis or prevention of rare diseases. Orphan Drug Designation provides some benefits such as financial incentives required to support clinical development and the potential for upto seven years of market exclusivity for the drug for the designated orphan disease in the United States if the drug is ultimately approved for its designated disease.

On October 20, 2022, AUM Biosciences and Mountain Crest Acquisition Corp. V, declared that they have entered into a definitive business combination agreement. Upon closing the transaction, the companies will operate under a holding entity, AUM Biosciences Limited, a Cayman Islands exempted company, and plans to trade on the Nasdaq Stock Market under the ticker symbol AUMB.

X4 Pharmaceuticals Announces Positive Top-line Results for WHIM Syndrome Drug

X4 Pharmaceuticals, declared positive top-line results from the global, pivotal Phase III clinical trial, 4WHIM of its lead investigational therapy, mavorixafor (a novel CXCR4 antagonist) in people with WHIM syndrome.

Key Top-Line 4WHIM Trial Results:

  • When measuring TATANC, or the amount of time that participants’ absolute neutrophil counts stayed above a clinically significant threshold of 500 cells per microliter over 24-hour periods at four different points during the 52-week trial, mavorixafor showed statistical and clinical superiority over placebo. The mean TATANC in the therapy group was 15.04 hours compared to 2.75 hours in the placebo group.
  • The TATALC, or the period of time that participants’ absolute lymphocyte counts remained above a clinically significant threshold of 1,000 cells per microliter, over 24-hour periods at four different time points throughout the 52-week trial, was another important secondary endpoint that was also met by 4WHIM, with mavorixafor showing statistical and clinical superiority over placebo. In the therapy group, the mean TATALC was 15.80 hours compared to 4.55 hours in the placebo group.
  • Through 52 weeks, increases in TATANC and TATALC remained higher than baseline and the placebo, showing the treatment’s efficacy.

In the trial, Mavorixafor was generally well tolerated; there were no significant adverse events associated with the treatment and no discontinuations for safety events.

More than 90% of the eligible individuals chose to receive treatment with mavorixafor in the open-label trial extension after the placebo-controlled section of the trial was completed.

The 4WHIM trial’s secondary and exploratory endpoints are currently being further reviewed and analysed, and additional findings will be presented at a subsequent medical meeting.

The X4’s interim Chief Medical Officer, Murray Stewart added, “Mavorixafor is the first and only oral investigational therapy to show reliable improvements in severe chronic neutropenia and lymphopenia, the hallmarks of the WHIM syndrome.”

“Following the achievements of these key trial endpoints, we are now getting ready to meet with United States regulatory authorities in the first half of 2023 to discuss further steps in advancing mavorixafor towards a submission for regulatory approval and commercialization as the potential first treatment for people suffering with WHIM syndrome.”

Nkarta Announces Updated Clinical Data on Anti-CD19 Allogeneic CAR-NK Cell Therapy NKX019

Harnessing the power of natural killer (NK) cells to attack cancer is an unproven strategy in oncology but one that is gaining traction as clinical trials begin to generate data. Nkarta has recently reported new results from an early-stage trial of one of its CAR-NK therapies, which will likely add to the field’s excitement. A medium or high dose of its lead, CD19-targeting CAR-NK therapy candidate NKX19 achieved complete responses in 7 out of 10 patients with relapsed or refractory non-Hodgkin lymphoma (NHL), driving their cancer into remission.

The complete responses occurred despite the patients having an extensive, aggressive disease that had progressed despite a median of four previous lines of therapy, according to Nkarta in an update on the trial, which included patients with various forms of NHL, such as large B cell lymphoma, mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma. A lower dose of CAR-NK resulted in a complete response in 1 of 4 NHL patients, but no responses were observed in a group of five patients with either acute lymphoblastic leukemia or chronic lymphocytic leukemia.

It believes CAR-NK therapies will be easier to tolerate than CAR-T therapies and will have the added benefit of being an off-the-shelf therapy, eliminating the time-consuming cell harvesting, production, and re-infusion process required with current CD19-targeting CAR-Ts such as Novartis’ Kymriah (tisagenlecleucel), Gilead Sciences’ Yescarta (axicabtagene ciloleucel), and Bristol (lisocabtagene maraleucel).

The company is now moving forward with dose expansion cohorts to investigate combination and single-agent regimens in patients with large B cell lymphoma to “address the large unmet need in patients who have received prior autologous CAR T therapy.” These will begin in 2024.

Eisai Presents the Full Phase III Trial Results of lecanemab for Alzheimer’s Disease at CTAD

Following the announcement of two lecanemab-related deaths on the eve of the Clinical Trials on Alzheimer’s Disease (CTAD) 2022 conference, Eisai has now published the full results of its phase III confirmatory Clarity AD study for early Alzheimer’s disease in the New England Journal of Medicine (NEJM).

The full findings of Eisai’s large, global phase III confirmatory Clarity AD clinical trial of lecanemab – an investigational anti-amyloid beta (A) protofibril antibody for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD), with confirmed presence of amyloid pathology in the brain – were presented at CTAD in San Francisco, California and simultaneously published in the prestigious NEJM

The Clarity AD phase III placebo-controlled, double-blind, parallel-group, randomized study enrolled 1,795 people with early Alzheimer’s disease across North America, Europe, and Asia. There were 898 in the lecanemab group and 897 in the placebo group. Stratification was based on a clinical subgroup (MCI due to AD or mild AD), presence or absence of concomitant approved AD symptomatic medication at baseline – such as acetylcholinesterase inhibitors, memantine, or both – as well as ApoE4 status and geographical region.

The results showed that deaths occurred in 0.7% and 0.8% of participants in the lecanemab and placebo groups, respectively, and that no deaths were associated with lecanemab or amyloid-related imaging abnormalities (ARIA) during the 18-month study period. Based on the phase IIb results, lecanemab’s ARIA incidence profile was within expectations. Eisai and Biogen both co-commercialize and co-promote lecanemab, with Eisai making the final decision.

EQRx Announces Acceptance of MAA by the EMA for Aumolertinib in EGFR-Mutated NSCLC

On December 02, 2022, EQRx, Inc. announced that the European Medicines Agency (EMA) has accepted for review its marketing authorization application (MAA) for aumolertinib. EQRx’s Aumolertinib is a third-generation irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in development as a first-line treatment option in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutations, and for adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC. 

The Marketing Authorization Application of Aumolertinib, is based on the data from the pivotal Phase 3 AENEAS trial evaluating the therapy in the first-line treatment of locally advanced or metastatic EGFR-mutated NSCLC. AENEAS (NCT03849768) is a randomized, double-blind, multicenter, Phase 3 study designed to evaluate the efficacy and safety of aumolertinib versus gefitinib as first-line treatment for adults with locally advanced or metastatic EGFR-mutated NSCLC. The study was conducted by Hansoh Pharma and enrolled 429 patients who were randomized to receive either aumolertinib (n=214) or gefitinib (n=215). 

Melanie Nallicheri, president and chief executive officer of EQRx has said, “this acceptance is an important milestone for aumolertinib, and for EQRx, as we focus on improving and broadening patient access to today’s therapeutic innovations within this class of medicines,”. This is EQRx’s second submission to a regulatory agency for aumolertinib. UK’s Medicines and Healthcare products Regulatory Agency is reviewing the Aumolertinib’s MAA  in EGFR-mutated NSCLC. Moreover, National Medical Products Administration (NMPA) of China has approved Aumolertinib as both first-line and second-line treatment of patients with locally advanced or metastatic EGFR-mutated NSCLC.

Aumolertinib is being investigated in several ongoing clinical trials, including studies in first- and second-line EGFR-mutated NSCLC. Aumolertinib was discovered by Hansoh Pharma. EQRx has partnered with Hansoh Pharma on the global development of aumolertinib to end global access to the therapy. As per the agreement, EQRx holds the development and commercialization rights to aumolertinib outside Greater China.

Lung cancer was the third most diagnosed cancer in Europe and also the leading cause of cancer-related mortality, accounting for one-fifth of cancer deaths. As per the estimate, globally, about a third of patients with NSCLC, which accounts for approximately 85% of all lung cancers, have EGFR mutations. As per the estimate, approximately 60,000 European patients may be diagnosed with EGFR-mutated NSCLC annually. If approved, aumolertinib can create a potentially differentiated option for patients with EGFR-Mutated Non-small Cell Lung Cancer in Europe.

FDA Approves Olutasidenib for IDH1-Mutated Relapsed/Refractory Acute Myeloid Leukemia (AML)

On Dec. 1, 2022, Rigel Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved REZLIDHIA™ (olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) Acute Myeloid Leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. The FDA approval was based on the data from the open-label Phase 2 registrational study evaluating REZLIDHIA monotherapy at a dose of 150 mg twice daily in 153 mIDH1 R/R AML patients.

Rigel is assessing REZLIDHIA, as a non-intensive monotherapy treatment in the relapsed/refractory AML setting and demonstrated a CR+CRh rate of 35% in patients, with over 90% of those responders in complete remission. REZLIDHIA is an oral, small molecule and an inhibitor of mutated IDH1 designed to bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells. The primary endpoint was a composite of complete remission (CR) plus complete remission with partial haematological recovery (CRh).

Earlier in August 2022, Rigel and Forma Therapeutics, Inc. announced that they had signed an exclusive, worldwide license agreement to develop, manufacture and commercialize REZLIDHIA. As per the agreement, Rigel will be responsible for the launch and commercialization of REZLIDHIA in the US and intends to work with potential partners to develop further and commercialize the product outside the U.S.As per DelveInsight, Acute myeloid leukemia (AML), is one of the most common types of leukemia in adults. Still, AML is fairly rare overall, accounting for only about 1% of all cancers. Despite the new therapies, several limitations are associated with the current treatment option available in the market.  The approval of the REZLIDHIA™ (olutasidenib) is expected to further improve the treatment scenario for patients with relapsed or refractory (R/R) Acute Myeloid Leukemia (AML).