Pembrolizumab

Today, a brief rundown of news from the Food and Drug Administration and Intellia Therapeutics, as well as updates from United Therapeutics, the Department of Health and Human Services and Merck & Co. that you may have missed.The Food and Drug Administration issued 30 warning letters to telehealth companies for making false or misleading claims about GLP-1 products offered on their websites. The new batch of letters is the second round the agency has sent since September, and warns companies making claims of sameness with FDA-approved medicines while obscuring product sourcing. The announcement comes amid a broader crackdown on pharmaceutical ads by the agency and a recent step-up in threats against GLP-1 copycats after Hims & Hers short-lived attempt to launch a compounded version of Novo Nordisks Wegovy pill.U.S. regulators on Monday also cleared Intellia Therapeutics to resume a Phase 3 trial evaluating one of its experimental gene editing treatments against transthyretin amyloidosis with cardiomyopathy, a progressive heart condition. The study is one of two late-stage trials that were paused last year following the death of a participant. Both have now been cleared to restart with new safeguards and, in the latest case, updating the study protocol to exclude patients with a recent history of certain heart problems.Intellia shares initially climbed by more than 10% before falling back.A pulmonary arterial hypertension drug from United Therapeutics lowered the risk of patients disease worsening by 55% compared to a placebo in a Phase 3 trial, positioning the company to seek approval later this year. The drug, ralinepag, is a newer type of prostacyclin receptor agonist, a therapy designed to help widen blood vessels in people with the condition. The results exceeded expectations and compare favorably with what was observed in testing of another prostacyclin therapy, Johnson & Johnsons Uptravi, wrote Leerink Partners Roanna Ruiz. United acquired ralinepag via a 2018 icensing deal with Arena Pharmaceuticals.Health and Human Services Secretary Robert F. Kennedy Jr. appointed two new members to the key federal panel, ACIP, that guides U.S. vaccine policy. One new appointee is Sean Downing, a Florida-licensed primary care physician who works in concierge medicine. The other is Angelina Farrella, a pediatrician and owner of a medical practice in Webster, Texas. The two have joined a committee thats been overhauled over the last year and since weakened multiple longstanding vaccine recommendations, drawing criticism from major medical organizations as well as, recently, a lawsuit from 15 Democrat-led states. The panels next meeting is scheduled for March 18.Merck & Co. on Saturday detailed a pair of study results that could help broaden the use of its kidney cancer drug Welireg. In one study, adding Welireg to Mercks immunotherapy Keytruda after surgery to remove a tumor reduced the risk of disease progression or death by 28% when compared to Keytruda alone. In the other, Welireg and Eisais Lenvima cut that same risk by 30% versus Exelixis Cabometyx in people who relapsed after treatment with Keytruda. The results, which Merck first announced without specifics last year, position the Welireg regimens to rapidly become standard-of-care treatments in their respective settings, wrote Leerinks Daina Graybosch. The Leerink team is predicting more than $3.4 billion in U.S. peak sales for Welireg, which Merck acquired in a 2019 buyout. '

US-based biopharma Inovio Pharmaceuticals and China-based Akeso, Inc. announced a clinical collaboration to evaluate a glioblastoma combination therapy pairing Inovio’s DNA medicine candidate INO-5412 with Akeso’s bispecific antibody cadonilimab. The collaboration will assess the combination in a Phase II adaptive platform trial in patients with glioblastoma multiforme (GBM), the most common and lethal primary brain malignancy in adults. Financial terms of the collaboration were not disclosed. The collaboration centers on two distinct immunotherapy assets contributed by each party. Inovio contributes INO-5412, a combination regimen comprising INO-5401, a DNA plasmid encoding three tumor-associated antigens (hTERT, WT1, and PSMA), and INO-9012, a DNA plasmid encoding the pro-inflammatory cytokine interleukin-12 (IL-12). Akeso contributes cadonilimab, also known as AK104, a PD-1/CTLA-4 bispecific antibody (BsAb) designed to achieve dual immune checkpoint blockade with a single molecule. The combination will be studied within the INSIGhT adaptive platform trial framework. Each company retains ownership of its respective drug candidate with no commercial rights involved in the deal. Scientific rationale for the glioblastoma combination regimen The pairing of INO-5412 with cadonilimab reflects a strategy to address GBM’s immunosuppressive tumor microenvironment from multiple angles. INO-5412 is designed to generate antigen-specific cytotoxic T lymphocyte responses against GBM cells expressing hTERT, WT1, and PSMA, while the IL-12 component encoded by INO-9012 is intended to amplify and sustain those responses by promoting a pro-inflammatory milieu at the tumor site. Cadonilimab’s simultaneous blockade of PD-1 and CTLA-4 is intended to release the brakes on T cell activity that the tumor microenvironment imposes through checkpoint-mediated suppression. The rationale for combining these modalities rests on the hypothesis that antigen-directed immune priming (via INO-5412) paired with checkpoint de-repression (via cadonilimab) could produce a more durable anti-tumor response than either approach alone. This is particularly relevant in GBM, where single-agent checkpoint inhibitors have so far failed to demonstrate survival benefits in randomized trials. Development status of participating molecules Inovio has been developing INO-5412 in GBM for several years, previously reporting interim and progression-free survival data from a Phase I/II trial of the combo regimen used in conjunction with cemiplimab (Regeneron’s PD-1 inhibitor) in newly diagnosed GBM patients at the ASCO Annual Meeting in 2022. The collaboration with Akeso marks a shift from a monospecific PD-1 antibody to bispecific targeting. The move to a dual-checkpoint agent reflects the broader oncology field’s interest in whether simultaneous PD-1 and CTLA-4 blockade can overcome resistance patterns observed with PD-1 monotherapy in GBM immunotherapy treatment settings. Cadonilimab has been developed primarily in China across multiple solid tumor indications, including cervical cancer, non-small cell lung cancer, hepatocellular carcinoma, gastric cancer, and esophageal cancer. The molecule’s Fc-null design is intended to reduce Fc-mediated effector functions that can contribute to immune-related adverse events, a persistent limitation of combining separate PD-1 and CTLA-4 antibodies. The GBM indication represents a new therapeutic frontier for cadonilimab. Akeso has not previously disclosed clinical activity for this asset in brain tumors. The blood-brain barrier and the immunologically privileged nature of the central nervous system present distinct pharmacological challenges that will need to be addressed in the trial design. Competitive landscape for GBM immunotherapy GBM remains one of the most treatment-resistant cancers. The standard of care has not changed materially in two decades and consists of maximal safe surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide. Median survival is approximately 15 to 18 months, and nearly all patients experience recurrence. Several other immunotherapy approaches are in clinical testing for GBM. Immunomic Therapeutics is evaluating ITI-1001, a multi-antigen DNA vaccine, in a Phase I trialin newly diagnosed GBM. Roswell Park Cancer Institute has advanced SurVaxM, a survivin-targeting peptide vaccine, into Phase II testing. None of these programs have yet advanced to late-stage registration trials. In the checkpoint inhibitor space, nivolumab failed to demonstrate an overall survival benefit over bevacizumab in the CheckMate 143 trial in recurrent GBM, and pembrolizumab has shown limited single-agent activity in this indication. The combination of a tumor-antigen-directed vaccine with a bispecific checkpoint inhibitor, as proposed in the Inovio-Akeso collaboration, represents a mechanistically distinct approach that has not been tested previously in GBM.