Bristol Myers Squibb Enhances Neuroscience Arm with Karuna Therapeutics Buyout

Bristol Myers Squibb has declared the finalization of its purchase of Karuna Therapeutics, Inc. With this acquisition concluded Karuna’s shares are no longer being traded on the Nasdaq Global Select Market, as Karuna is now fully owned by Bristol Myers Squibb.

“We are thrilled to broaden our range of neuroscience offerings with the addition of Karuna to Bristol Myers Squibb,” stated Chris Boerner, Ph.D., Chief Executive Officer of Bristol Myers Squibb. “Crucially, this agreement supports our dedication to enhancing BMS’s growth prospects for the latter part of this decade and beyond. We are eager to collaborate with the skilled team at Karuna to introduce KarXT to individuals with schizophrenia later in the current year.”

Through this deal, BMS has acquired KarXT (xanomeline-trospium), an antipsychotic showcasing a new method of action along with a distinctive efficacy and safety profile. Additionally, BMS has gained access to Karuna’s early-stage and pre-clinical pipeline. KarXT is slated for a Prescription Drug User Fee Act (PDUFA) decision on September 26, 2024, specifically for treating schizophrenia in adults. Furthermore, KarXT is currently undergoing trials for its use as an adjunctive therapy alongside existing standard treatments for schizophrenia, as well as for treating psychosis in Alzheimer’s patients. There is potential for its application to broaden into other conditions such as Bipolar I disorder and agitation in Alzheimer’s disease.

The deal will be recorded as acquiring an asset, leading to a one-time, non-deductible charge of around $12 billion for Acquired In-Process Research and Development (Acquired IPR&D). This will affect both the first quarter and full-year 2024 GAAP and non-GAAP earnings per share by roughly $5.93.

FDA Greenlights Orchard Therapeutics’ Lenmeldy for Young Patients with Metachromatic Leukodystrophy

Orchard Therapeutics, which was recently acquired by Kyowa Kirin to speed up the delivery of new gene therapies to patients worldwide, has announced that the FDA has given approval for Lenmeldy (atidarsagene autotemcel), previously known as OTL-200. This approval is for treating children who have pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ), or early symptomatic early juvenile (ESEJ) forms of metachromatic leukodystrophy (MLD)—all collectively known as early-onset MLD.

Bobby Gaspar, M.D., Ph.D., co-founder and CEO of Orchard Therapeutics, expressed that the FDA’s approval of Lenmeldy presents significant new opportunities for children in the U.S. facing early-onset MLD, a condition for which there were previously no treatment options beyond supportive and end-of-life care. Dr. Gaspar emphasized the severe impact of MLD, a rare disease that progresses rapidly, limits life, and is ultimately fatal, affecting children and families profoundly. He acknowledged that this achievement results from years of dedicated research and development in collaboration with the San Raffaele-Telethon Institute for Gene Therapy. Dr. Gaspar extended sincere appreciation to the patients and families involved in clinical trials, as well as to the wider MLD community, recognizing their invaluable contributions and support as pivotal to reaching this milestone.

Lenmeldy’s goal is to address the root genetic cause of MLD by placing one or more fully functional copies of the human ARSA gene into a patient’s own hematopoietic stem cells (HSCs) outside the body, using a lentiviral carrier. These genetically corrected cells are then reintroduced into the patient’s system. Once they take hold, these cells develop into various cell types, including some that move through the blood-brain barrier into the central nervous system, where they produce the needed enzyme. This method could potentially revive enzyme function, halting or reducing the advancement of the disease with just one therapy.

Lenmeldy received Priority Review status in September 2023. Before this, it had been awarded Rare Pediatric Disease (RPD) and Regenerative Medicine Advanced Therapy (RMAT) designations by the FDA. Orchard Therapeutics was granted a Priority Review Voucher (PRV) alongside the approval, which is set to be transferred to GSK as per the conditions of the initial licensing agreement.

Madrigal Pharmaceuticals’ Rezdiffra Secures FDA Approval for Noncirrhotic NASH with Moderate to Advanced Liver Fibrosis Treatment

Madrigal Pharmaceuticals, Inc. has reported that the FDA has given accelerated approval for Rezdiffra (resmetirom) when used alongside diet and exercise. This approval is for treating adults who have noncirrhotic NASH with moderate to advanced liver fibrosis (corresponding to stages F2 to F3 fibrosis). Further approval for this use may depend on confirming and describing the clinical benefits in ongoing trials.

Bill Sibold, Madrigal’s CEO, expressed that NASH, a liver disease marked by moderate to advanced fibrosis, has been a severe and progressing condition lacking FDA-approved treatments until now. The fast-tracked approval of Rezdiffra is the result of over 15 years of research led by Dr. Becky Taub, the company’s founder, and a small research and development team. Tackling one of the most significant challenges in drug development, marks a pivotal moment for the NASH field, showcasing the potential of the industry. Sibold added that they are eager to provide Rezdiffra to patients in need.

Rezdiffra, a daily oral THR-β agonist, is engineered to address core factors contributing to NASH. Its fast-track approval came after the Phase III MAESTRO-NASH study, recently published in the New England Journal of Medicine. This pivotal trial continues, involving 1,759 NASH patients confirmed through biopsy. Over 52 weeks, both the 100 mg and 80 mg Rezdiffra doses significantly outperformed a placebo on two main measures: resolving NASH (with a decrease in NAFLD activity score by ≥2 points) without worsening fibrosis and enhancing fibrosis by at least one stage without worsening NAFLD activity score. These benefits were consistent across different demographics like age, gender, presence of type 2 diabetes, or stage of fibrosis.

Rezdiffra is anticipated to be accessible for US patients starting in April, with distribution managed via a restricted specialty pharmacy network. Madrigal is dedicated to assisting suitable patients who could benefit from Rezdiffra by facilitating access through the Madrigal Patient Support initiative. This initiative aims to guide patients through insurance and financial obstacles, offering co-pay aid for those eligible. Additionally, Madrigal has initiated a patient assistance program (PAP) to aid uninsured patients in obtaining access to Rezdiffra.

AstraZeneca’s Acquisition of Amolyt Pharma Boosts Advancements in Late-Stage Rare Disease Treatments

AstraZeneca has revealed its plans to buy Amolyt Pharma, a biotech firm in the clinical stage that concentrates on creating new therapies for rare endocrine illnesses. This acquisition aims to strengthen the Alexion and AstraZeneca Rare Disease late-stage development pipeline. It will also broaden its expertise in bone metabolism by adding eneboparatide (AZP-3601), a Phase III experimental peptide with a unique way of working that targets important treatment objectives for hypoparathyroidism. Furthermore, Alexion is eager to incorporate the skilled team members from Amolyt Pharma into its fold.

Marc Dunoyer, CEO of Alexion, AstraZeneca Rare Disease, expressed that individuals with chronic hypoparathyroidism urgently require an alternative to current supportive treatments, as these fail to address the root cause of hormone deficiency. With Alexion’s expertise in rare diseases, they are well-placed to advance the late-stage development and worldwide distribution of eneboparatide. This drug has the potential to reduce the often severe effects of low parathyroid hormone levels and eliminate the risks associated with high-dose calcium supplements. Dunoyer believes that this initiative, in collaboration with Amolyt’s skilled team and promising pipeline, will facilitate their expansion into the realm of rare endocrine disorders.

Eneboparatide, acting as an agonist for the PTH receptor 1 (PTHR1), operates through an innovative mechanism tailored to address the treatment objectives of hypoparathyroidism. Phase II findings demonstrated that eneboparatide not only restored serum calcium levels to normal but also showed promise in potentially removing the need for daily calcium and vitamin D supplements. Among adults grappling with chronic hypoparathyroidism alongside hypercalciuria, eneboparatide was observed to bring about a normalization of calcium levels in urine. Furthermore, in individuals with hypoparathyroidism, eneboparatide safeguarded bone mineral density, offering a significant potential advantage for those at heightened risk of osteopenia or osteoporosis.

Prilenia Aims for EU Marketing Approval of Pridopidine for Huntington’s Disease

Prilenia Therapeutics B.V. has revealed intentions to present a Marketing Authorization Application (MAA) for pridopidine to the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP), aiming for its approval for treating Huntington’s disease. This announcement comes after productive pre-submission discussions with EU regulatory bodies, with the submission slated for mid-2024.

Dr. Michael R. Hayden, CEO of Prilenia, stated that Pridopidine consistently shows beneficial effects in various areas important to patients and their families. These include everyday functioning, cognition, motor skills, and clinical advancement in individuals with Huntington’s disease. The advantages are particularly clear in HD patients who do not use anti-dopaminergic medications (ADM). Hayden expressed gratitude for the productive discussions with European regulators concerning their pridopidine data. This progress offers a potential path toward approving a therapy for Huntington’s disease, a rare neurodegenerative condition marked by a predictable decline and a current lack of approved treatments that address its progression. The company is now finalizing its submission for Marketing Authorization Application (MAA) by mid-2024 and preparing to make pridopidine available for commercial use among patients in Europe, pending approval.

ADMs encompass neuroleptics (alternatively termed antipsychotics) and VMAT2 inhibitor (anti-chorea) medications. Prilenia aims to engage in discussions with the FDA regarding potential avenues for pridopidine as a prospective treatment for individuals with Huntington’s disease in the United States. The company also plans to explore regulatory submissions globally for other countries and regions after the regulatory assessment process in Europe. Apart from advancements in Huntington’s disease, Prilenia disclosed in January 2024 that it had concluded talks with regulatory bodies worldwide concerning the next developmental phase of pridopidine for amyotrophic lateral sclerosis (ALS) and is preparing for a singular pivotal Phase III trial.