Rare Disease

Vertex Pharmaceuticals announced new interim data showing that ALYFTREK, or vanzacaftor/tezacaftor/deutivacaftor, restored exocrine pancreatic function in some children with cystic fibrosis ages 2 to 5, allowing them to stop pancreatic enzyme replacement therapy. The data, presented as a late breaker poster at the North American Cystic Fibrosis Conference, came from 48 children enrolled in the PERT discontinuation substudy VX22-121-106 Cohort 2, part of an ongoing open-label extension study in that age group. After at least 48 weeks of treatment, mean fecal elastase-1 was 239.7 micrograms per gram, a mean increase of 110.2 micrograms per gram from baseline, and 48.6 percent of children reached the pancreatic sufficiency threshold of at least 200 micrograms per gram. Of the 48 children eligible for the substudy, 18, or 37.5 percent, successfully discontinued pancreatic enzyme replacement therapy for a mean duration of 8.6 weeks, and across the full enrolled cohort of 66 children, 50 percent were not on the therapy at the data cut. Carmen Bozic, Vertex's chief medical officer, said the findings represent a profound shift in understanding the benefits of treating cystic fibrosis in its earliest stages, noting that pancreatic failure had long been considered irreversible. Vertex also presented additional abstracts at the conference, held October 7 to 10 in Atlanta, on clinical and real-world evidence for CFTR modulators, including a post-hoc analysis of reduced intravenous antibiotic use with VNZ/TEZ/D-IVA in patients 12 and older and a natural history study of exocrine pancreatic function in infants under 12 months. The use of ALYFTREK in children 2 to 5 years old is investigational.

Scholar Rock has resubmitted its Marketing Authorisation Application for apitegromab to the European Medicines Agency for the treatment of children and adults with spinal muscular atrophy. The resubmitted application replaces the Catalent Indiana fill-finish facility with Scholar Rock's alternate fill-finish facility, the same U.S.-based site that supported the September 2026 FDA approval of ISEMBYLD, also known as apitegromab-mstn. The company withdrew its previous MAA in August 2026 after a lack of GMP compliance at the Catalent Indiana facility, and now anticipates a Committee for Medicinal Products for Human Use opinion in the first half of 2027. Chief Executive Officer David L. Hallal said the company is working with urgency to bring this first-ever muscle-targeted therapy to children and adults living with SMA in Europe, where more than 35,000 SMA patients globally are receiving an SMN-targeted therapy. Apitegromab is the first and only muscle-targeted treatment to demonstrate motor function improvement in individuals with SMA currently receiving a survival motor neuron 2-targeted treatment, based on the Phase 3 SAPPHIRE study.

The pheochromocytoma and paraganglioma market across the United States, EU4, the United Kingdom and Japan is projected to grow from approximately USD 300 million in 2025 to approximately USD 670 million by 2036, a CAGR of 7.3% during 2026-2036, according to a new ResearchAndMarkets.com report. The United States represented the largest regional market, generating approximately USD 200 million in 2025, and Merck's belzutifan, sold as WELIREG, is forecast to generate the highest PCPG therapy revenue in the United States by 2036. WELIREG, a selective HIF-2a inhibitor and the first oral targeted PCPG therapy, was approved in May 2025 for adult and pediatric patients aged 12 years and older with locally advanced, unresectable or metastatic PCPG, at a US list price of USD 31,162.50 per bottle of 90 tablets, or an estimated annual cost of USD 373,950. Approximately 4,900 incident PCPG cases were reported across the 7MM in 2025, including around 2,400 in the United States, and the report notes that pipeline rivals from Novartis, Jazz Pharmaceuticals and Perspective Therapeutics are advancing, including LUTATHERA, JZP3507 and VMT-a-NET.

The US FDA has granted orphan drug designation to vTv Therapeutics' oral sickle cell candidate HPPD. In preclinical studies, the first-in-class Nrf2/Bach1 modulator increased fetal hemoglobin and reduced oxidative stress and red blood cell sickling. The company noted that in those studies, the fetal hemoglobin increase was seen in a time- and dose-dependent manner, and effects were comparable to or better than hydroxy urea.

Bristol Myers Squibb is counting on Reblozyl, the thalassemia drug it co-developed with Merck, to help drive top-line growth as legacy drug sales decline, with the treatment's sales nearing $1.3 billion in the first half of 2026, up 23% from the year-ago period. The drug's strong sales reflect solid uptake in first-line MDS-associated anemia, continued strength in the second-line setting and further penetration in the first-line RS-negative population. The FDA has accepted a supplemental biologics license application for Reblozyl with concomitant janus kinase inhibitor therapy in adult patients with myelofibrosis-associated anemia receiving red blood cell transfusions, supported by the late-stage INDEPENDENCE study, and granted a target action date of March 11, 2027. A phase III study called ELEMENT-MDS, evaluating Reblozyl in first-line non-transfusion dependent low or intermediate risk MDS associated anemia, is ongoing, with data expected in 2028. In the competitive landscape, Geron Corporation's Rytelo generated $57.5 million of revenues in the second quarter of 2026 and is expected to post 2026 sales of $220-$240 million, while Keros Therapeutics expects a $20 million development milestone payment from partner Takeda after dosing the first patient in the late-stage ELRiSE MF study.

Rocket Pharmaceuticals said it has a clear path to complete a pivotal phase 2 trial for its Danon disease asset RP-A501. Twelve male patients will receive treatment, with co-primary endpoints of myocardial LAMP2 protein expression of at least Grade 1 and a reduction in left ventricular mass index of at least 10% from baseline after one year. If those endpoints are met, Rocket could seek a potential accelerated approval pathway. Phase 1 results showed that at around 12 months, the six patients in the main phase 1 analysis had myocardial LAMP2 protein expression and at least a 10% reduction in left ventricular mass index. At follow-up of three to seven years, left ventricular mass index was below baseline in five of six patients, with reductions of at least 10% in four patients. Danon disease is a rare genetic disorder characterized by cardiomyopathy and muscle weakness.

Shionogi & Co., Ltd. announced that its Board of Directors approved an agreement to acquire IntraBio Inc., a biopharmaceutical company developing and commercializing therapies for neurodegenerative diseases, for an upfront consideration of USD 2.0 billion payable to IntraBio shareholders. Under the agreement signed on October 5, 2026, IntraBio would become a wholly owned subsidiary of New Jersey-based Shionogi Inc., with the transaction scheduled to close between November 2026 and December 2026, subject to competition-law waiting periods and other customary conditions. The deal would add AQNEURSA (levacetylleucine) to Shionogi's rare disease portfolio; the drug was approved by the FDA in September 2024 for neurological manifestations of Niemann-Pick disease type C and by the European Medicines Agency in January 2026, and on September 18, 2026 it became the first and only FDA-approved treatment for Ataxia in patients with Ataxia-Telangiectasia, for which it is also under EMA review. Shionogi said the acquisition builds on the rare disease foundation it established through its April 2026 acquisition of global rights to edaravone, known as RADICAVA in the U.S. and RADICUT in Japan, and would strengthen its pipeline across Pompe disease, Fragile X syndrome, Jordan's syndrome and early-stage rare neurodegenerative programs. The impact on Shionogi's consolidated financial results for the fiscal year ending March 2027 is currently under review.

CSL and Alentis Therapeutics have entered an exclusive global partnership to co-develop and co-promote lixudebart for rare kidney, liver, and other diseases. Under the agreement, CSL will arrange an initial payment of $355M to Alentis, which is also eligible for up to $1.2B in commercial milestone payments, bringing the total deal value to $1.55B. The companies will share global profits 55% to CSL and 45% to Alentis once the drug is commercialized. CSL will fund Phase 2 and planned Phase 3 studies of lixudebart in AAV-RPGN while advancing Phase 2 programs in FSGS and PSC. Lixudebart is currently being evaluated in the Phase 2 RENAL trial for AAV-RPGN, a rare autoimmune disease that can cause rapid kidney function loss and irreversible kidney damage.

AnnJi Pharmaceutical announced it is proceeding with the U.S. portion of its pivotal Phase 3 ROMA-KD trial of AJ201, also known as rosolutamide, in patients with spinal and bulbar muscular atrophy, or SBMA, also called Kennedy's disease. The company said it submitted the Phase 3 protocol to the U.S. FDA under its active Investigational New Drug application and will now activate U.S. sites for the global trial. The ROMA-KD study is a global, multicenter, randomized, double-blind, placebo-controlled trial expected to enroll approximately 200 ambulatory patients with symptomatic SBMA worldwide, with the United States as a key region, and is intended to support potential global regulatory submissions. AJ201, an investigational oral small molecule and a potential first-in-class treatment for SBMA, has received Fast Track Designation from the U.S. FDA and Orphan Drug Designation in both the United States and the European Union. AnnJi said the Phase 3 program builds on encouraging results from its completed Phase 2 study announced in May 2025, and the company also noted its SBMA Patient and Care Partner Advisory Council, first announced in collaboration with the Kennedy's Disease Association at the 2026 KDA International Patient and Scientific Conference.

Wells Fargo initiated coverage of Design Therapeutics with an overweight rating, citing the company's Friedreich ataxia candidate DT-216P2 as having potentially best-in-disease functional improvement based on results from the RESTORE-FA study released in May. The bank set a $26 price target, implying roughly 112% upside based on the October 1 close. Analyst TianQi Hang wrote that the May update showed pharmacokinetics look good, and that blood-FXN protein, muscle-mRNA data, plus an early mFARS signal further de-risk the platform. Hang estimates that the blood FXN protein increase seen after 6 weeks can translate to at least a 2-point mFARS change, and said that if the drug kinetics sustain for 12 weeks, which he believes they will, DT-216P2 could deliver best-in-disease functional benefits. He assigns DT-216P2 a 60% probability of success, with peak sales of approximately $600M in the US and approximately $900M outside it. If approved, DT-216P2 would compete against Biogen's Skyclarys, also known as omaveloxolone, and Hang sees it gaining a peak share of the FA treatment market of 30% in the US and 20% ex-US.

The US FDA has approved Bristol Myers Squibb's Camzyos, also known as mavacamten, for children with symptomatic obstructive hypertrophic cardiomyopathy, a rare genetic heart condition that can cause shortness of breath, fatigue, and abnormal heart rhythm. The approval was based on results of the phase 3 double-blind, placebo-controlled SCOUT-HCM trial, which enrolled children 12 to 18 years old with symptomatic oHCM; patients in the Camzyos arm had a significantly reduced Valsalva LVOT gradient, a measure of pressure in the left ventricular outflow tract while bearing down, compared to placebo. Camzyos carries a boxed warning for heart failure risk and is restricted through a Risk Evaluation and Mitigation Strategy program. The treatment was approved for adults in 2022.

argenx SE announced it will present new clinical, long-term and real-world data across its neuromuscular portfolio at the 2026 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting and the Myasthenia Gravis Foundation of America Scientific Session in Orlando, Florida, from September 29 to October 2, 2026. In myasthenia gravis, Phase 3 ADAPT OCULUS data showed ocular MG improvements deepened with additional VYVGART cycles, with mean MGII ocular scores improving from -4.5 to -6.8 points in AChR-Ab-positive patients and from -2.7 to -4.5 points in triple-seronegative patients, while one-year ADAPT SERON results showed mean MG-ADL improvements of approximately 5 points maintained through Week 52 in anti-AChR antibody-negative generalized MG. A real-world analysis of more than 1,100 U.S. MG patients found patients treated within a year of diagnosis had a mean MG-ADL reduction of 4.7 points over the first three months versus 3.5 points for those treated more than three years after diagnosis, with 50% reaching minimal symptom expression. In CIDP, an interim analysis of ADHERE and ADHERE+ showed approximately 40% of responding participants reached an INCAT score of 0 or 1 with follow-up beyond five years, a post hoc analysis found VYVGART Hytrulo reduced the relative risk of grip strength deterioration by 71.5%, and a Phase 4 switch study showed 87% of patients remained on VYVGART Hytrulo through 12 weeks after a one-week direct transition from IVIg. The company also reported sustained clinical benefit and consistent safety for empasiprubart in multifocal motor neuropathy from the Phase 2 ARDA+ study, and in-clinic and real-world walking improvements for adimanebart in DOK7-congenital myasthenic syndrome from a Phase 1b study.

Aptadir Therapeutics has closed a EUR 40M Seed round to advance a novel class of RNA inhibitor-based therapeutics for intractable genetic conditions. The round was led by 4BIO Capital, with follow-on participation from the company's original pre-seed investor EXTEND, Italy's National Technology Transfer Hub launched by CDP Venture Capital SGR and jointly funded by Angelini Ventures and Evotec SE. Additional support came from CDP Venture Capital through the Digital Transition Fund, Indaco Venture Partners, XGEN Venture, CE-Ventures, Angelini Ventures through a direct investment, Kerna Ventures, Italian Angels for Biotech, and Club degli Investitori. The funds will advance the company's pipeline of disease-modifying investigational RNA therapeutics, including its lead candidate CAP1-FMR1 for Fragile X Syndrome, based on a new class of RNAs called DNMTs Interacting RNAs that block aberrant DNA methylation at a single gene level to reactivate silenced gene expression. The science originates from the Beth Israel Deaconess Medical Center, the Italian Research National Council, and the Cancer Science Institute of Singapore.

Truist analyst Danielle Brill identified a significant positive readthrough for Maze Therapeutics following positive Phase 2 topline data from Vertex Pharmaceuticals, validating APOL1 inhibition in classic APOL1-mediated kidney disease and supporting an addressable population of over 100,000 patients. Truist reiterated a Buy rating and $64 target on Maze, noting the market is large enough to support blockbuster potential for Maze's MZE829 even if efficacy merely matches Vertex's inaxaplin. Maze reported $494.9 million in cash, cash equivalents, and marketable securities in Q2 2026, funding its Phase 2 HORIZON trial of MZE829 with cohort updates expected in late 2026 or early 2027 and a pivotal trial planned for H1 2027. Vertex, which posted $3.33 billion in Q2 2026 revenue, up 12% year-over-year, and holds $13.6 billion in cash and marketable securities, raised its full-year 2026 revenue guidance to $13.1–$13.2 billion. Maze faces late-mover risk behind inaxaplin and reported a Q2 2026 net loss of $44.7 million, while Vertex's R&D and SG&A expenses reached $1.6 billion in Q2 2026.

Biogen's growth portfolio generated $1.06 billion in second-quarter 2026 revenues, up 24% year over year and 25% sequentially, surpassing the company's legacy MS portfolio, which brought in $767 million. Even excluding newly acquired Syfovre and Empaveli, growth-product revenues reached $933 million, up 9% year over year and 10% quarter over quarter, still above the legacy MS portfolio. Within the growth portfolio, Skyclarys revenues rose 29% to $168 million, Zurzuvae increased 53% to $71 million, Spinraza grew 2% to $402 million, and Vumerity fell 7.4% to $196.5 million, while Syfovre and Empaveli contributed $97.4 million and $30.4 million respectively. Alzheimer's collaboration revenues from Eisai for Leqembi rose 16% to $63.7 million, and the companies expect blood-based diagnostics and the launch of Leqembi Iqlik to drive further growth from 2027 onward. Biogen expects the growth portfolio to maintain its lead in the second half of 2026, with Syfovre and Empaveli contributing more than in the second quarter since revenue recognition began only in mid-May.

Oryzon Genomics, S.A. announced that the European Medicines Agency has authorized its Clinical Trial Application to initiate a Phase II study of vafidemstat for the treatment of Phelan-McDermid Syndrome. The study, named HOPE-2, is a single-center, single-arm, open-label Phase IIa trial that will enroll 12 adult patients with PMS, a severely disabling genetic disorder related to autism with a U.S. prevalence estimated at approximately 1 in 7,300 people. The primary objective is to evaluate the safety and tolerability of vafidemstat, with secondary objectives assessing its effect on anger and aggression and overall disease efficacy; vafidemstat will be administered for 12 weeks, after which the investigator will assess whether participants may continue treatment through week 24 based on clinical benefit. The study will be conducted in Spain as part of Oryzon's VANDAM project, which is part of the Med4Cure Important Project of Common European Interest on Health and has received funding from the Spanish Ministry of Science, Innovation and Universities and the Centre for the Development of Industrial Technology and Innovation under the Recovery, Transformation and Resilience Plan funded by the European Union – NextGenerationEU. Oryzon will collaborate with the Spanish Phelan-McDermid Syndrome Association to support identification of potential participants.

The United States Food and Drug Administration granted platform technology designation to Precigen's AdenoVerse immunotherapeutic platform, which underpins the recently approved PAPZIMEOS therapy. The designation and the earlier PAPZIMEOS approval have coincided with a sharp shift in market sentiment toward Precigen, with the share price delivering an 81.07% year-to-date return and a three-year total shareholder return exceeding 4x, while the more recent 90-day share price return of 32.25% indicates momentum has been building. The stock last closed at $7.75, and the most followed analyst view puts fair value at $11, framing the rally as only a partial catch up. On that view, bearish analysts expect earnings to reach $253.7 million, or $0.68 per share, by about August 2029, up from $336.7 million of losses today, while more bullish analysts expect earnings as high as $363.7 million. On a sales-based measure, the stock trades at 32.4x sales against a US Biotechs group average closer to 12.1x and a fair ratio of 9.5x, a gap that points to valuation risk if sentiment or forecasts change.

The US FDA on Friday approved Mirum Pharmaceuticals and Incyte's Atebrioz, also known as zilurgisertib, as a treatment for the rare bone condition fibrodysplasia ossificans progressiva, or FOP. The oral activin receptor-like kinase 2 inhibitor is designed to reduce the volume of total new heterotopic ossification in adults and children 12 years and older. Approval was based on results from a cohort of the PROGRESS study that showed at week 24, mean total new heterotopic ossification lesion volume decreased by 3.2 cm³ in patients receiving Atebrioz compared with an increase of 24.6 cm³ in those on placebo, with benefits maintained through week 48 of the open-label extension. FOP is an ultra-rare, progressive genetic disease impacting approximately 300 people in the US and approximately 900 worldwide, characterized by heterotopic ossification in which bone forms in muscles, tendons, ligaments, and other soft tissues.

Sanofi's new and acquired drugs are emerging as a broadening growth base beyond its flagship immunology medicine Dupixent, with sales of those newer products rising 48.3% at constant exchange rates to €1.3 billion in the second quarter, led by Altuviiio, Ayvakit and Sarclisa. Dupixent, marketed in partnership with Regeneron, remains the company's primary growth engine and accounted for roughly 42% of Sanofi's first-half 2026 revenues. Altuviiio achieved blockbuster sales in 2025, while Ayvakit, added through the Blueprint Medicines acquisition, is expected to become the next blockbuster drug in 2026, and Beyfortus, developed with AstraZeneca, reached blockbuster sales in its first full year in 2024. Sanofi now expects its Pharma launches to generate approximately €10 billion of annual sales by 2030, compared with about €25 billion for Dupixent, as it positions the newer medicines to gradually reduce reliance on its top-selling drug. The Zacks Consensus Estimate for 2026 earnings has risen from $4.96 per share to $5.07 per share over the past 60 days, while 2027 estimates climbed from $5.18 to $5.29 per share, and Sanofi stock has fallen 15.5% year to date against an 11.7% gain for the industry.

Prime Medicine shares jumped 8% Friday after the FDA cleared its IND application for PM647, an experimental gene-editing therapy for Alpha-1 Antitrypsin Deficiency. The clearance allows Prime Medicine to begin a Phase 1/2 trial evaluating PM647 in adults with the inherited disorder, with initial clinical data expected in 2027. PM647 is designed to fix the genetic mutation that causes Alpha-1 Antitrypsin Deficiency, and Prime Medicine said the treatment could restore the normal protein and potentially help treat both the lung and liver problems caused by the disease.

Vertex Pharmaceuticals is building a differentiated kidney disease franchise to diversify beyond its dominant cystic fibrosis business, with povetacicept and inaxaplin seen as significant commercial opportunities. Povetacicept, added through the approximately $4.9 billion acquisition of Alpine Immune Sciences in 2024, targets the BAFF and APRIL cytokines, and the FDA accepted a regulatory filing for its use in IgA nephropathy in June 2026, with a final decision expected on Nov. 30, 2026. If approved, povetacicept would become Vertex's first marketed nephrology product, addressing an estimated 330,000 people with IgAN in the United States and Europe and more than 1.5 million diagnosed patients globally, with analysts forecasting blockbuster sales and peak annual revenues in the multi-billion-dollar range. Inaxaplin is being developed in the phase II/III AMPLITUDE study in primary APOL1-mediated kidney disease, with enrollment complete and interim data expected in early 2027, while data from the phase II AMPLIFIED study announced earlier this week showed a 42.7% reduction in urine albumin to creatinine ratio at week 13 in patients with AMKD and modest proteinuria, and a 17.3% reduction in those with AMKD and type II diabetes. The IgA nephropathy space has grown more competitive, with the FDA already approving Otsuka's Voyxact, Vera Therapeutics' Trutakna and Novartis' Vanrafia.

Otsuka Pharmaceutical and U.S.-based Ionis Pharmaceuticals announced on the 22nd that their jointly developed treatment for hereditary amyotrophic lateral sclerosis, ulefnersen, met its primary goal in a late-stage clinical trial. In patients with FUS mutation ALS, a rare inherited form of ALS that damages the nerve cells controlling movement, ulefnersen improved function and extended survival compared with the placebo group. The drug reduced markers of nerve cell damage and slowed disease progression, and most side effects were mild or moderate, indicating a favorable safety profile. No approved treatment currently targets the genetic cause of FUS-ALS, and the two companies plan to discuss the results with the U.S. Food and Drug Administration and global health authorities as they explore a path toward accelerated approval. Separately, Otsuka Pharmaceutical has launched a global early access program for FUS-ALS patients unable to participate in the trial, allowing physicians to request access to ulefnersen before approval.

Arcturus Therapeutics said interim phase 2 results for ARCT-810 showed the candidate reduced and/or maintained first morning fasting ammonia within the normal range in patients with ornithine transcarbamylase deficiency, and also reduced glutamine, with some individuals reaching the normal range. Based on those results and a June meeting with the US FDA, the company aims to begin dosing of ARCT-2601 close to the end of the year in participants 12 years and older under an amended phase 2 protocol that integrates ARCT-2601 into the current ARCT-810 phase 2 study. Both ARCT-810 and ARCT-2601 are mRNA therapeutics for OTC deficiency, but ARCT-810 uses the LUNAR platform while ARCT-2601 uses the next-generation LUNAR 2.0 platform, which Arcturus says produces greater than 30-fold higher protein expression and could allow for lower or less frequent dosing. OTC deficiency is a rare genetic disorder in which the body stops breaking down and removing nitrogen, leading to dangerous ammonia levels in the blood. Arcturus is also acquiring AI discovery company myNeo, with which it has worked since 2024, and the deal is expected to close in October.

Roche Holding partner Ionis reported that sefaxersen met the primary endpoint in the Phase 3 IMAgINATION trial for IgA nephropathy, delivering a statistically significant reduction in proteinuria compared with placebo. The clinical win comes on top of a strong run for Roche Holding, with the share price up 8.32% over 90 days and 11.58% year to date, and a 1-year total shareholder return of 44.02%. Roche Holding now trades at CHF363.20, only about 3% below the average analyst target, yet screens at a roughly 59% discount to an intrinsic value estimate, while the most followed narrative fair value of CHF353.34 pegs the stock as 2.8% overvalued. The SWS DCF model points the opposite way, implying a future cash flow value of CHF893.70. The story could still change quickly if key Phase 3 programs disappoint or if biosimilar pressure on older blockbusters accelerates faster than expected.

Ionis Pharmaceuticals announced positive late-stage results from two partnered phase III programs. The FUSION study of ulefnersen in amyotrophic lateral sclerosis caused by mutations in the fused in sarcoma gene met its primary endpoint assessing functional impairment and survival at 72 weeks, with Ionis reporting the results as statistically significant without disclosing supporting numbers; Otsuka Pharmaceutical, which holds worldwide commercialization rights licensed in 2024, plans to discuss the data with the FDA and other global health authorities regarding potential expedited regulatory submission pathways. Separately, the IMAgINATION study of sefaxersen in adults with primary immunoglobulin A nephropathy, conducted by Ionis' partner Roche, met its primary endpoint in a prespecified interim analysis, showing statistically significant and clinically meaningful reductions in proteinuria after 37 weeks, and will continue in a blinded manner to evaluate kidney function over two years with estimated glomerular filtration rate at week 105 as the longer-term measure. Roche licensed sefaxersen from Ionis in 2022 and is responsible for the phase III study and future global development, regulatory and commercialization activities, while Ionis is eligible for milestone payments and tiered royalties on net sales of both drugs. The two wins follow back-to-back cardiovascular setbacks for Ionis, including the phase III CARDIO-TTRansform failure of Wainua with AstraZeneca in July and the phase III Lp(a)HORIZON miss for pelacarsen with Novartis, and come after the FDA approval of Zanvastro for Alexander disease earlier this month. Year to date, Ionis shares have lost 42% compared with the industry's 2% decline.