Cellerys

A couple of months after getting its self-administered multiple sclerosis drug Kesimpta cleared by EU regulators, Novartis has found what it believes is “the next frontier” of MS treatment at a University of Zurich spinout — and it’s already laying the groundwork for a buyout. Novartis struck a deal to develop Cellerys’ cell therapy CLS12311, which is designed to induce antigen-specific immune tolerance in MS patients, the pharma said on Tuesday. The drugmakers have been in talks for several years, according to a Novartis spokesperson, and upon completion of a Phase II trial in “coming years,” the pharma will have a chance to acquire Cellerys. The drugmakers didn’t release many details, other than to say that Novartis will “support the development” of CLS12311, and they’re keeping the financial terms of the deal under wraps for now. “Immune tolerance therapies offer the potential to intervene early and decisively in the development of MS, to potentially stop progression of the disease,” the spokesperson told Endpoints News in an email. Cellerys was founded in 2015 by University of Zurich professors and MS specialists Roland Martin and Andreas Lutterotti. CLS12311 was shown to be safe and well-tolerated in a Phase I trial at the University Hospital Zurich, according to Novartis, and it’s now in Phase II for relapsing MS — the same indication that Kesimpta snagged an FDA approval for back in August. Kesimpta — Novartis’ B-cell therapy also known as ofatumumab — was approved by the EC in March, several months after it was given the OK in the US. Novartis originally got the drug from GlaxoSmithKline in their big vaccines-for-cancer therapies swap, but had a hard time selling it as a leukemia therapy. In MS, the drug showed a 51% and 59% reduction in annualized relapse rate compared to Sanofi’s Aubagio in ASCLEPIOS I and II, winning over regulators after a delayed decision. The treatment can be administered at home, which gave it a leg up on rivals that require a trip to an infusion center — and Novartis charges for that convenience. Back in August, the pharma announced Kesimpta’s wholesale price would be $83,000. That’s much higher than Roche’s rival Ocrevus, which hit the market at a discounted price of $65,000. In Q1 of this year, Kesimpta pulled in $50 million.

Harold Cunningham/Getty Images The early termination of the Beovu trials places a damper on Novartis’ hopes of competing even further with Regeneron Pharmaceuticals’ retinal disease drug Eylea. Novartis put a hold on further studies of Beovu. (Harold Cunningham/Getty Images) Novartis has cut three Phase III trials of its eye therapy Beovu (brolucizumab) after the studies showed higher rates of intraocular inflammation with frequent dosing intervals of the therapy. The early termination of the trials places a damper on Novartis’ hopes of competing even further with Regeneron Pharmaceuticals ’ retinal disease drug Eylea. Novartis is halting the MERLIN trial as well as the RAPTOR and RAVEN studies because of safety concerns. In these trials, investigators evaluated safety and efficacy outcomes after four-week Beovu dosing intervals. The company said it would amend all “relevant ongoing trial protocols” to discontinue the four-week dosing intervals following the loading phase. Beovu is an approved retinal disease therapy indicated for age-related macular degeneration (AMD) in over 60 countries. Currently, ongoing trials are investigating whether the drug holds promise in wet AMD, proliferative diabetic retinopathy, and diabetic macular edema. In MERLIN, treatment with Beovu met the trial’s primary endpoint of non-inferiority for the change in best-corrected visual acuity. The drug also met superiority on specific anatomical secondary endpoints at one-year follow-up compared with aflibercept when administered every four weeks after the loading phase. Treatment with Beovu at 6 mg every four weeks in the MERLIN trial, however, was associated with more frequent incidences of retinal vasculitis and retinal vascular occlusion compared with the aflibercept 2 mg arm. Additionally, the overall vision loss rate was proportionally higher in the Beovu group (4.8% vs. 1.7%). “Although longer dosing intervals may benefit many people living with wet AMD and other retinal diseases, some are in need of monthly dosing to address persistent fluid. We initiated MERLIN and other clinical programs to explore Beovu for these patients,” said Novartis’ Global Head of Drug Development and Chief Medical Officer, John Tsai, MD, in a statement. “These data help inform our trials moving forward, so we can best determine how appropriate patients can benefit most from this important medicine.” Despite these adverse effects, Novartis maintains Beovu is still an effective and clinically significant therapy for patients with wet AMD, at least when given on a two- to three-month interview after the loading phase. The company states it will continue to further analyze MERLIN trial data to understand its full range of effects in patients. Novartis said in its statement on the study terminations that it has communicated the adverse event data to health authorities and is planning to provide an update to global Beovu prescribing information. The shutdown of the three trials hasn’t swayed Novartis from making noticeable business moves, including signing a recent collaboration agreement that features an option to acquire Zurich-based startup Cellerys. The collaboration agreement with Cellerys gives Novartis the option of buying out the former Swiss biotech, which is currently developing CLS12311, a multiple sclerosis drug in phase II trials. Reuters reports that Novartis will support the development of CLS12311 under the agreement and “will have the option to acquire Cellerys upon completion of a Phase 2 trial in the coming years.” The two companies have not released any financial details on the deal.

Harold Cunningham/Getty Images Novartis has cut three Phase III trials of its eye therapy Beovu (brolucizumab) after the studies showed higher rates of intraocular inflammation with frequent dosing intervals of the therapy. The early termination of the trials places a damper on Novartis' hopes of competing even further with Regeneron Pharmaceuticals' retinal disease drug Eylea. Novartis is halting the MERLIN trial as well as the RAPTOR and RAVEN studies because of safety concerns. In these trials, investigators evaluated safety and efficacy outcomes after four-week Beovu dosing intervals. The company said it would amend all "relevant ongoing trial protocols" to discontinue the four-week dosing intervals following the loading phase. Beovu is an approved retinal disease therapy indicated for age-related macular degeneration (AMD) in over 60 countries. Currently, ongoing trials are investigating whether the drug holds promise in wet AMD, proliferative diabetic retinopathy, and diabetic macular edema. In MERLIN, treatment with Beovu met the trial's primary endpoint of non-inferiority for the change in best corrected visual acuity. The drug also met superiority on specific anatomical secondary endpoints at one-year follow up compared with aflibercept when administered every four weeks after the loading phase. Treatment with Beovu at 6 mg every four weeks in the MERLIN trial, however, was associated with more frequent incidences of retinal vasculitis and retinal vascular occlusion compared with the aflibercept 2 mg arm. Additionally, the overall vision loss rate was proportionally higher in the Beovu group (4.8% vs. 1.7%). "Although longer dosing intervals may benefit many people living with wet AMD and other retinal diseases, some are in need of monthly dosing to address persistent fluid. We initiated MERLIN and other clinical programs to explore Beovu for these patients," said Novartis' Global Head of Drug Development and Chief Medical Officer, John Tsai, MD, in a statement. "These data help inform our trials moving forward, so we can best determine how appropriate patients can benefit most from this important medicine." Despite these adverse effects, Novartis maintains Beovu is still an effective and clinically significant therapy for patients with wet AMD, at least when given on a two- to three-month interview after the loading phase. The company states it will continue to further analyze MERLIN trial data to understand its full range of effects in patients. Novartis said in its statement on the study terminations that it has communicated the adverse event data to health authorities and is planning to provide an update to global Beovu prescribing information. The shutdown of the three trials hasn't swayed Novartis from making noticeable business moves, including signing a recent collaboration agreement that features an option to acquire Zurich-based startup Cellerys. The collaboration agreement with Cellerys gives Novartis the option of buying out the former Swiss biotech, which is currently developing CLS12311, a multiple sclerosis drug in phase II trials. Reuters reports that Novartis will support the development of CLS12311 under the agreement and "will have the option to acquire Cellerys upon completion of a Phase 2 trial in the coming years." The two companies have not released any financial details on the deal.