PCRX-201 is the first gene therapy product candidate to receive RMAT designation for osteoarthritis --
-- Designation supported by encouraging preliminary data from 72-patient Phase 1 study --
-- 52-Week Data Accepted for Presentation at OARSI 2024 and 104-week data to be submitted for presentation later this year --
Allogene Therapeutics and Arbor Biotechnologies on Tuesday announced that they entered into a non-exclusive global gene editing licensing deal to develop allogeneic CAR-T therapies for autoimmune diseases.
The collaboration agreement “provides us access to Arbor’s proprietary gene-editing technology and know-how,” Allogene CMO Zachary Roberts said in a statement, adding that the partnership will help the company develop “the most effective and broadly accessible CAR T approach for the treatment of autoimmune disease.”
The licensing deal will bring together Allogene’s CAR T expertise with Arbor’s proprietary CRISPR gene-editing technology. Using AI techniques with high-throughput screening, Arbor engineers novel genomic editors that leverage the CRISPR-Cas9 system to deliver therapeutically relevant levels of editing efficiency, according to the biotech’s website.
Arbor’s approach allows it to use various technology platforms—from gene knockouts to large insertions and precision editing—giving it a “robust set of tools” to most effectively target specific disease.
Allogene and Arbor did not disclose the specific financial terms of the deal or the division of responsibilities, nor did they reveal what autoimmune indication they would target.
Arbor’s next-generation gene-editing technology has also attracted Vertex Pharmaceuticals, which in 2018 paid $30 million upfront to target cystic fibrosis. In January 2023, Vertex expanded the partnership, allowing for up to three disease targets.
For its part, Allogene will leverage its AlloCAR T platform, which makes use of T cells from healthy donors engineered to express CARs that recognize and destroy the target cells.
By combining these technologies, the partners aim to reduce or completely remove chemotherapy conditioning typically required for the treatment of autoimmune diseases. Allogene expects to launch a Phase I study for its first AlloCAR T investigational product in early 2025.
For Allogene, the Arbor pact comes as it refines its pipeline priorities. In January 2024, the biotech announced that it would focus its allogeneic CAR-T development on four main programs: large B-cell lymphoma, chronic lymphocytic lymphoma, renal cell carcinoma and autoimmune diseases.
Its autoimmune disease program is led by ALLO-329, a CD19 product that targets B-cells and CD70-positive activated T-cells, both of which are known to play a role in autoimmune diseases.
As part of its new pipeline strategy and resource reallocation, Allogene eliminated 22% of its headcount.
Novartis is acquiring IFM Due, a subsidiary of privately held IFM Therapeutics, with the biotech getting $90 million in an upfront payment and remaining eligible for up to $745 million in milestone payments, the companies announced Wednesday.
This is not the first deal between the companies. In September 2019, IFM forged an option and collaboration deal with Novartis, which saw the Swiss pharma make fixed payments to finance R&D costs for the program in exchange for the option to acquire the company.
Under Wednesday’s acquisition, Novartis now has the full rights to IFM Due’s portfolio of STING antagonists, which can potentially treat inflammation-driven diseases “characterized by excessive interferon” and other pro-inflammatory cytokine signaling, according to the announcement.
“The acquisition of IFM Due represents the culmination of a highly productive, four-year preclinical collaboration between Novartis and IFM to develop novel small-molecule STING inhibitors with the potential to treat a spectrum of inflammatory diseases,” Richard Siegel, global head of immunology research at Novartis, said in a statement. “We are excited to advance IFM Due’s STING program and leverage our deep expertise in inflammation science to bring forward transformative medicines that address major unmet patient needs.”
Other deals between Novartis and IFM have also been made. In April 2019, the Swiss pharma acquired subsidiary IFM Tre, paying $310 million upfront and another $1.26 billion in various milestones. That deal was focused on developing NLRP3 antagonists for treating inflammatory diseases.
Novartis has made other acquisition and licensing moves this year. In February 2024, it bought German biotech MorphoSys for around $2.9 billion, expanding its oncology offerings.
In January 2024, Novartis entered a strategic collaboration and licensing deal with Voyager Therapeutics, paying $100 million upfront and $1.2 billion in potential milestones. The deal will see the development of gene therapies for Huntington’s disease and spinal muscular atrophy.
A Phase II clinical trial of Ionis Pharmaceuticals’ metabolic dysfunction-associated steatohepatitis drug candidate has hit its primary endpoint, the company said Wednesday.
Investigators randomized 160 people with metabolic dysfunction-associated steatohepatitis (MASH), the liver disease formerly known as nonalcoholic steatohepatitis, to receive placebo or one of three doses of ION224 subcutaneously once a month. Ionis designed the ligand-conjugated antisense medicine to cut production of DGAT2, an enzyme that studies have linked to fatty liver disease.
After 51 weeks, the proportion of patients who had MASH histologic improvement without worsening of fibrosis was significantly higher in the top two dose cohorts than in the placebo group. The significant differences caused the trial to meet its primary endpoint.
Ionis shared the p values for the successful 90-mg and 120-mg doses—0.015 and less than 0.001, respectively—but is yet to provide a closer look at the primary endpoint data. Subgroup analyses found patients with both F2 and F3 fibrosis, the middle scores on a four-point scarring severity scale, improved after taking ION224.
The biotech published some secondary endpoint data. ION224 beat placebo on an endpoint that looked at MASH resolution without worsening of fibrosis, as measured by biopsy. At the highest dose, 44% of patients had a 50% or greater relative reduction in liver steatosis, as measured by imaging, while 3% of people on placebo experienced such an improvement.
Ionis also saw a trend favoring ION224 for a liver scarring endpoint. In the high-dose arm, 32% of people had at least a one stage improvement in fibrosis without worsening of steatohepatitis as measured by biopsy, compared to 12.5% of their peers in the placebo cohort.
The FDA asks sponsors to show a one stage improvement in fibrosis with no worsening of MASH or the resolution of MASH with no worsening of fibrosis in Phase III clinical trials. The first wave of MASH assets failed to clear that bar but recent studies have fared better, with Madrigal Pharmaceuticals hitting both the endpoints in Phase III. The FDA is set to decide whether to approve Madrigal’s resmetirom by Thursday.
The success of resmetirom, a THR-β agonist, in clinical trials is part of a series of events that suggest Ionis will face competition if it delivers its own pivotal study victory and brings ION224 to market. Companies are working on MASH molecules against a range of targets, from Boehringer Ingelheim’s glucagon/GLP-1 receptor dual agonist survodutide to Akero Therapeutics’ FGF21 analog efruxifermin.
Other companies are interested in Ionis’ MASH target, DGAT2. Pfizer axed one DGAT2 inhibitor after Phase I but still has another candidate, PF-06865571, in mid-stage development. Data from the Phase II clinical trial are imminent, according to ClinicalTrials.gov. Other companies including Sinew Pharma and Viking Therapeutics are working on DGAT1 inhibitors.
Bristol Myers Squibb’s Abecma and Johnson & Johnson’s Carvykti may be facing potential resistance from the FDA as the respective CAR-T therapies head into Friday’s advisory committee meeting with the regulator’s panel of outside experts, according to briefing documents from the FDA’s staff.
The agency is interested in the advisory committee’s opinion regarding the “higher rate of early deaths” for both Abecma and Carvykti in their respective trials, the documents state.
For Abecma, the document noted that there was a higher rate of early deaths in the treatment arm of the trial.
“The adequacy of exploratory analyses of the KarMMa-3 trial to support the identification of strategies to mitigate this risk warrants further discussion. Retrospective subgroup analyses, which are not pre-specified at the initiation of the study and not supported by an adequate sample size, cannot adequately characterize a heterogeneous patient population,” the FDA staff stated in the document.
The regulator also said that an analysis of the reasons for death is varied but includes an “inability to proceed with the first treatment step” as well as leukapheresis, manufacturing failure, disease progression and adverse events, among other reasons.
In the Carvykti briefing document, the FDA said the trial that was conducted—Cartitude-4—has shown “early detriment” in overall survival in the treatment arm, and an increased rate of early death is reflected in the Kapan-Meier curves as a “crossing hazards pattern favoring the standard therapy arm up to approximately 11 months; heavy censoring limits the estimation of the treatment effect on overall survival after 11 months.”
However, J&J remains positive about the trial results going into Friday’s advisory committee meeting.
“We are confident in the data from the Phase III Cartitude-4 study and look forward to reviewing survival and safety data with the FDA Oncologic Drugs Advisory Committee,” Brian Kenney, the global oncology and R&D communication leader at J&J, told BioSpace in an emailed statement. “We are committed to working with the FDA in the continued clinical development of Carvykti with a focus on bringing this immunotherapy to patients with multiple myeloma earlier in the course of the disease. We remain confident that the overall benefit-risk profile of Carvykti remains favorable in treating patients with relapsed/refractory multiple myeloma.”
BMS was not immediately available to respond to BioSpace’s request for comment.
Friday’s advisory committee meeting comes as the FDA has been looking deeper into the safety issues around CAR-T therapies. Since November of last year, the agency has been investigating the risk of secondary malignancies in patients who have received CD19-directed or BMCA-autologous CAR-T therapies. Global regulators are also increasingly scrutinizing the therapies.
Eli Lilly is enlisting the help of Amazon Pharmacy to fill prescriptions of its blockbuster weight-loss treatment Zepbound (tirzepatide), according to several media reports on Wednesday.
Under the arrangement, Amazon Pharmacy will deliver prescriptions of Zepbound—as well as Lilly’s migraine and diabetes medicines—to patients who ordered them via the pharma’s end-to-end digital health portal LillyDirect. Amazon can deliver orders out within two days for certain patients, according to CNBC.
Amazon Pharmacy is LillyDirect’s second online dispensing partner, following the digital health start-up Truepill. The bulk of online orders will be split between the two distributors, with final fulfillment carried out according to the customers’ insurance provider and other personal details.
CNBC reported that Lilly expects Amazon and Truepill to have similar processing times.
Amazon makes for a good distribution partner for Lilly because of its “experience in developing tech-enabled solutions,” Frank Cunningham, vice president of global value and access at Lilly, told Endpoints News. “We liked their commitment to patient safety, simplifying the pharmacy experience and great customer service.”
Lilly is also mulling a partnership with a retail pharmacy to allow for pick-up options for orders placed on LillyDirect, Cunningham told Reuters.
Launched in January 2024, LillyDirect is an online platform that caters to U.S. patients with obesity, migraine and diabetes. LillyDirect offers customers a “digital pharmacy” for some of the company’s medicines and is designed to provide consistent access to prescription access, along with the convenience of home delivery.
LillyDirect’s online pharmacy solutions are also meant to help patients access the company’s affordability and savings opportunities, according to Lilly.
The digital health platform also provides access to independent telehealth providers to complement patients’ existing care teams, as well as educational information. Lilly will continue to expand LillyDirect and future updates may include new products, partners and other services, the company said.
Lilly’s digital push comes as the pharma continues to ride the sky-high demand for obesity therapies. Currently, Lilly and Novo Nordisk—which owns the semaglutide products Wegovy and Ozempic—have a virtual duopoly on the obesity space and are poised to capture the vast majority of the potential $200 billion market in the coming years.
Several companies are also eyeing a slice of the massive weight-loss market including Regeneron, which is advancing a pair of muscle-preserving antibodies designed to improve the quality of weight loss when used in conjunction with the current GLP-1 receptor agonists.
Also in the race is Amgen, which has a Phase I candidate called MariTide that last month showed longer-lasting effects than current therapies on the market. Boehringer Ingelheim is also looking to challenge Lilly and Novo with its glucagon/GLP-1 receptor dual agonist survodutide, for which it launched three Phase III trials in August 2023.
THARROS is the first-ever prospective trial to investigate the potential of an inhaled triple therapy to reduce cardiopulmonary events, a key driver of mortality, in COPD
First patients dosed in ATHLOS Phase III trial assessing impact of BREZTRI on integrated cardiopulmonary parameters associated with health status and survival in patients with COPD
https://finance.yahoo.com/news/astrazeneca-announces-initiation-tharros-phase-110600738.html
