Pegcetacoplan

Character Biosciences, a biotechnology startup developing treatments for vision loss, said Tuesday it raised $93 million in a Series B round.The financing will help Character bring its two most advanced programs into clinical testing. One, dubbed CTX114, is being tested in geographic atrophy, a common eye condition and an advanced stage of age-related macular degeneration, or AMD. The other, CTX203, is designed to halt progression in people with intermediate AMD, so they dont develop geographic atrophy or other forms of advanced disease. Both drug prospects should begin Phase 1 trials this year.In geographic atrophy, Character aims to challenge two marketed drugs Apellis Pharmaceuticals Syfovre and Astellas Pharmas Izervay. Both can slow the growth of the patchy, map-like eye lesions that create blind spots in people with geographic atrophy. However, testing hasnt clearly shown that doing so preserves vision. And in rare cases, Syfovre has been associated with severe side effects.Like Syfovre and Izervay, CTX114 works on the complement system, an arm of the bodys immune system. According to Character co-founder and CEO Cheng Zhang, CTX114 does so differently, mimicking the function of a protein that stops the complement system from overactivating, but that malfunctions in AMD. Preclinical testing has suggested the approach may be more effective, though that hasnt been proven in humans.Characters second drug is being developed for people who dont yet have advanced AMD and arent typically treated. CTX203 is designed to stabilize expression of a protein called ABCA1 thats involved in lipid transport by retinal cells. Lower ABCA1 levels are associated with an abnormal buildup of lipids that can lead to AMD progression.While there are many medications for wet AMD, drugmakers have had less success with the dry form that accounts for the bulk of the estimated 200 million people worldwide with the disease. Zhang says a big reason why is the diseases heterogeneity and varied progression, which makes it difficult to design clinical trials. Character has collected a trove of AMD patient data to help design its drugs and identify the specific groups of people it intends to enroll in studies.What gives us comfort is that we have mapped out those challenges, we have a deeper understanding of how we might mitigate those risks, Zhang said. We can subtype patients, understand those patients who are more likely to respond to our therapy, and have a drug that has more applications in the first place.Characters Series B round was led by aMoon and Luma Group, and involved Bausch + Lomb, Jefferson Life Sciences and four other investors. Bausch + Lomb also announced a collaboration with the biotech in January.Characters patient-first approach is unique in its ability to identify those who are most likely to benefit from therapy, and we look forward to seeing the clinical impact of this approach with the use of proceeds from this financing, Jamie Kasuboski, a partner and head of research at Luma Group, said in a statement.Character was formerly known as Clover Therapeutics, which was launched in 2019 by the health insurance firm Clover Health. The company previously raised an $28 million in funding, Zhang said. '

Novartis' Fabhalta may be the first approved for complement 3 glomerulopathy, but it may not be the only one soon, as Apellis is also angling its Empaveli for the same kidney disease. Novartis’ kidney disease troika keeps marching forward.With a new FDA approval, the company’s Fabhalta has become the first treatment endorsed by the agency for the ultrarare kidney disease complement 3 glomerulopathy (C3G). But analysts spotted several shortfalls in the drug’s label, leaving more to be desired—and potential room for improvement for rival Apellis.Thursday’s approval clears Fabhalta to reduce excessive protein in the urine—a phenomenon called proteinuria—in adults with C3G.“This approval of Fabhalta is historic for the entire C3G community as now, for the first time, we have a therapy that is believed to treat the underlying cause of the disease, providing the potential for a new standard of care for patients,” Carla Nester, M.D., at the University of Iowa, said in a statement.About one to two people per million worldwide are diagnosed with C3G each year, according to a Novartis estimate based on a 2020 study. The disease is marked by the buildup of C3 protein in the kidney glomeruli as a result of overactivation of the alternative complement pathway, triggering inflammation and kidney damage. Fabhalta works by inhibiting complement factor B, blocking activation of C3.Data from the phase 3 Appear-C3G trial initially showed that treatment with Fabhalta led to a statistically significant 35% relative reduction in proteinuria from baseline, as measured by 24-hour urine protein-to-creatinine ratio (UPCR), compared with placebo after six months. Nester was an investigator of the study.Then 12-month data found that Fabhalta’s proteinuria benefit was maintained after one year. And in patients who switched from placebo to Fabhalta, the magnitude of 24-hour UPCR improvement, at 31%, was similar to the outcome seen in the original Fabhalta group during a six-month testing period.C3G marks Fabhalta’s third U.S. indication, following its approval in paroxysmal nocturnal hemoglobinuria (PNH) in 2023 and IgA nephropathy (IgAN) last year.“It’s a molecule nephrologists already know, and we’re going to fully synergize our launch with the presence that we already have amongst these nephrologists,” Victor Bulto, president of Novartis U.S., said in an interview with Fierce Pharma ahead of the latest FDA approval. While Fabhalta is the first drug to enter the C3G field, it may soon have company. Apellis is also angling its Sobi-partnered C3 inhibitor Empaveli (pegcetacoplan) for a C3G nod. And by analysts’ observations, Apellis has better efficacy data.In the phase 3 Valiant trial, Empaveli led to a 68% relative reduction in proteinuria versus placebo after six months.Despite differences in trial design and baseline patient characteristics, analysts at Citi and William Blair view Empaveli as the winning C3G med between the two. And according to the team at William Blair, so too did Nester.Nester presented both trials’ results at the 2024 American Society of Nephrology Kidney Week conference in October. When asked about her expectation of commercial uptake for the two drugs, “she noted that physicians will be choosing based on efficacy, and pegcetacoplan has shown the best efficacy so would likely get the majority of patients,” William Blair analysts wrote in an October note.Novartis’ Bulto argued that C3G is a very heterogeneous disease, and the measurements of proteinuria can be highly variable, making cross-trial comparisons difficult.Rather than precise proteinuria numbers, doctors are really hoping to see stabilization of patients’ estimated glomerular filtration rate (eGFR), which is a key measurement of kidney function, Bulto argued.In Appear-C3G, Fabhalta appeared to confer eGFR stability through one year, compared with disease progression prior to treatment. However, the mean improvement of 1.3 mL/min/1.73m2 at six months was not statistically different from the 0.9 mL/min/1.73m2 deterioration seen with placebo.As the Fabhalta label now states, “there was no difference between arms in the proportion of patients with stable or improved eGFR compared to baseline at 6 months (90% in Fabhlata vs 89% in placebo).”That might be why the FDA’s approved indication for Fabhalta in C3G has specific language stating that it’s used “to reduce proteinuria.”In contrast, in Valiant, Empaveli showed a relative eGFR improvement of 6.3 mL/min/1.73m2 over placebo after six months. This represents an opportunity for Empaveli to earn a broader label without the proteinuria language, Evercore ISI analysts said in a Thursday note.However, to Bulto’s point of heterogeneity among C3G patients, Empaveli patients actually logged a 1.5 mL/min/1.73m2 eGFR decline from baseline in Valiant, although that was better than the 7.8 mL/min/1.73m2 drop seen in the placebo group. The Empaveli eGFR showing was not formally significant in Valiant thanks to the trial’s statistical design. Apellis’ study included adolescents. Novartis’ only enrolled adults, leading to an adult-only FDA label; Novartis has noted that the average age of diagnosis is around 23 years old. In addition, in the efficacy section, the FDA label specifies that Fabhalta’s profile has not been established in C3G patients following kidney transplant, whereas Empaveli has data in that population.“Overall, it looks to us like FDA label for [Novartis] includes specific language keeping the door open for [Apellis] to have a clearly differentiated label—on both breadth and efficacy,” the Evercore team said.There’s one potential advantage for Fabhalta, though—it’s an oral drug, while Empaveli is an injection.“We also hear from the patient community, if they can achieve that efficacy with an oral therapy, that's always a layer of preference as well,” Bulto said.Fabhalta is one of three meds that Novartis is developing against kidney diseases from different mechanisms of action. The company is also expecting an FDA decision on endothelin A receptor antagonist atrasentan in IgAN and is working on anti-APRIL antibody zigakibart.Commercially, Novartis is bringing “several products” and “several capabilities” in kidney diseases, Bulto noted. Apellis, in contrast, has one single asset here.