Cardiovascular & Heart-Failure Therapeutics

The U.S. Food and Drug Administration has approved an expanded indication for Bristol Myers Squibb's CAMZYOS (mavacamten) to treat symptomatic obstructive hypertrophic cardiomyopathy in adults and pediatric patients weighing 30 kg (66 lbs) or more, making it the only FDA-approved therapy for oHCM in a pediatric population and giving it the broadest indication of any cardiac myosin inhibitor. The approval is based on positive results from the Phase 3 SCOUT-HCM trial, which evaluated CAMZYOS (n=23) versus placebo (n=21) in patients aged 12 to under 18 years with symptomatic NYHA Class II-III oHCM. CAMZYOS met the trial's primary endpoint, showing a statistically significant reduction in Valsalva left ventricular outflow tract gradient at Week 28 compared with placebo, with a least-squares mean difference from placebo of minus 48.0 mm Hg (95% CI, minus 67.7 to minus 28.3; P<0.0001). No patients in SCOUT-HCM experienced left ventricular ejection fraction below 50%, no adverse events led to treatment discontinuation, and no new adverse reactions were identified beyond the safety profile observed in adults. CAMZYOS was first approved by the FDA in 2022 for adults with symptomatic NYHA class II-III oHCM and has been prescribed by more than 5,000 healthcare providers to over 25,000 patients in the U.S. alone; the pediatric data is now being discussed with multiple global regulatory authorities for potential pediatric indications.

Cantor Fitzgerald initiated coverage of Lexicon Pharmaceuticals at overweight, citing optimism over upcoming phase 3 data for the SGLT1/2 inhibitor Inpefa, also known as sotagliflozin, as a treatment for hypertrophic cardiomyopathy, with results expected in the first quarter of 2027. The firm set a price target of $8, which it said represents roughly 344% upside based on the September 27 close. Analyst Steve Seedhouse wrote that Inpefa is completely orthogonal to cardiac myosin inhibitors, where most of the recent innovation in HCM has come from, so it will complement rather than compete with those drugs, examples of which include Bristol Myers Squibb's Camzyos, or mavacamten, and Cytokinetics' Myqorto, or aficamten. Seedhouse added that background cardiac myosin inhibitors are allowed in the phase 3 study SONATA-HCM, so if SONATA-HCM works, sotagliflozin is essentially unencumbered competitively in a proven blockbuster market. He noted several potential ways SGLT and SGLT2 are involved in HCM, including reducing epicardial adipose tissue and mitochondrial oxidative stress and restoring glucose levels and ATP homeostasis. Inpefa is already approved to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure in adults with heart failure, or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.

B. Riley analyst Mayank Mamtani has identified six top biotech picks heading into third-quarter 2026 earnings season, following the Federal Reserve's 25 basis point rate hike to 4.00%, its first increase since July 2023. The unanimous 12-0 vote left room for one to two additional hikes before year-end, and with the 10-year Treasury at its highest level since 2007, small and mid-cap biotech stocks face a macro-driven drawdown that historically has presented buying opportunities. The XBI index is up 27% year-to-date but down 2% quarter-to-date, compared to the S&P 500's 13% and 4% gains respectively, while loss of exclusivity-driven pharma mergers and acquisitions track toward their strongest year since 2019, permanent FDA leadership is installed, and drug-pricing risk is largely resolved through most favored nation agreements covering 26 companies. Late third quarter and fourth quarter carry over 40 company-specific catalysts across the coverage list. The picks are Axsome Therapeutics, rated Buy with a $300 price target and up 6% year-to-date, where the analyst models AUVELITY revenue at approximately $205 million to $210 million against consensus of $215.8 million and total revenue of approximately $259 million; Cytokinetics, rated Buy with a $146 price target and up 4% year-to-date, with MYQORZO wholesale tracking to approximately $18 million for the full third quarter versus $8.9 million for all of second quarter; Eton Pharmaceuticals, rated Buy with a $70 price target and up 229% year-to-date, with consensus third-quarter 2026 and fiscal year 2026 revenue of $42 million and $149.7 million versus management's guidance of over $145 million for fiscal year 2026; Harrow, rated Buy with a $60 price target and down 31% year-to-date, with fiscal year 2026 guidance of $350 million to $365 million; TG Therapeutics, rated Buy with an $86 price target and up 95% year-to-date, positioned to compound off an approximately $1 billion U.S. Briumvi exit run-rate at year-end 2026; and Zymeworks, rated Buy with a $44 price target and up 4% year-to-date, where partner Jazz Pharmaceuticals' third-quarter 2026 report in early November provides the first commercial read on the first-line HER2-positive gastroesophageal adenocarcinoma launch following the August 25 approval and $250 million milestone.

Apollo Global Management is in discussions to acquire Johnson & Johnson's orthopedics business, DePuy Synthes, in a potential transaction valuing the unit at close to $20 billion, according to Bloomberg. The unit, which J&J previously announced plans to separate within an 18-to-24-month timeframe, generated $9.3 billion in 2025 revenue. An agreement could be reached within weeks, though J&J is also weighing a tax-efficient public market spin-off. For Apollo, the deal would deploy capital into a scaled medical technology franchise at roughly 2.2 times 2025 revenue, while for J&J an upfront cash sale would accelerate its pivot toward higher-growth areas such as Oncology, Immunology, and Cardiovascular. Risks include medical device litigation liabilities and integration complexity for Apollo, and sacrificed long-term cash flows for J&J.

Merck won an FDA label update adding HYPERION trial data for adults recently diagnosed with pulmonary arterial hypertension, sending shares up about 1.0% to $149.56 at 11.19am ET on Thursday. In the 320-person trial, Winrevair plus background therapy cut the risk of clinical worsening by 76% versus placebo, with first events occurring in 10.6% of treated patients compared with 36.9% of those receiving placebo. The broader label could support earlier use of the therapy, though commercial gains still hinge on diagnosis, insurance coverage and how long patients stay on treatment. Merck shares trade at $149.56, 23.8% above GuruFocus' $120.80 GF Value estimate.

Novo Nordisk is exploring the hair-loss market as the Ozempic and Wegovy maker looks to diversify beyond its blockbuster GLP-1 drugs. Chief Scientific Officer Martin Lange said Novo could leverage its scientific expertise to move into hair loss, though the company has not decided whether to pursue the market first. The comments came as Novo outlined plans to find new growth areas beyond its weight-loss franchise, targeting more than five drugs with multi-blockbuster potential by 2030 and expecting more than $23 billion in risk-adjusted pipeline sales by 2035. The company also plans to pursue bolt-on deals and accelerate development of treatments for heart, liver and blood disorders, as Eli Lilly has taken share in the injectable GLP-1 market and Novo faces a longer-term patent cliff for semaglutide, the active ingredient in Ozempic and Wegovy. Pattern hair loss affects an estimated 50 million men and 30 million women in the U.S., and no new FDA-approved therapy for the condition has emerged since the 1990s, according to the report.

Merck announced that the U.S. Food and Drug Administration has approved an update to the U.S. product label for WINREVAIR, also known as sotatercept-csrk, for injection at 45mg and 60mg, based on the Phase 3 HYPERION trial. In HYPERION, which enrolled 320 adults newly diagnosed with pulmonary arterial hypertension at intermediate to high risk of disease progression, adding WINREVAIR to background therapy reduced the risk of clinical worsening events by 76% compared with placebo, with a hazard ratio of 0.24 and a 95% confidence interval of 0.14 to 0.41 and a p value below 0.0001. A first clinical worsening event occurred in 10.6% of patients who received WINREVAIR, or 17 of 160, versus 36.9%, or 59 of 160, of those on placebo, and the mean time since PAH diagnosis was 7.2 months. The label update also adds safety information, including monitoring of hemoglobin and platelets before each dose for the first 5 doses, and notes that the most common adverse reactions in HYPERION were epistaxis at 31.9% versus 6.9%, telangiectasia at 26.3% versus 11.3% and increased hemoglobin at 11.3% versus 1.3%. Separately, Merck said the European Respiratory Society this month published clinical guidelines for the treatment of PAH that are the first formal clinical guidelines to include WINREVAIR, giving it a strong recommendation and grading the certainty of evidence as high.

Amgen's updated analyst model lifted its fair value price target to US$388.03 from a prior US$371.93, with the revenue growth assumption rising to 3.50% from 2.93%, the net profit margin assumption moving to 25.15% from 24.84%, the future P/E multiple changing to 25.1x from 24.6x, and the discount rate shifting to 7.96% from 7.70%. The revision reflects a split analyst view, with UBS, Argus, TD Cowen, Scotiabank and Oppenheimer raising their Amgen price targets into a US$420 to US$460 range on the strength of a strong product portfolio, Q2 beats and higher guidance. Wells Fargo and Piper Sandler lifted their targets to US$435, citing external survey work and prescription data they believe support higher long term sales potential for cholesterol and cardiovascular products such as Repatha and Lipfendra. On the bearish side, HSBC downgraded Amgen to Hold and cut its target to US$425 from US$445, saying the stock price now more closely matches its assessment of fair value with limited near term upside, while BMO Capital shifted to a neutral Market Perform stance even with a higher US$450 target, citing ongoing loss of exclusivity headwinds and a need for more clarity on the competitive profile and sales potential of MariTide.

Edwards Lifesciences outlined a structural heart growth plan that targets more than US$2 billion in transcatheter mitral and tricuspid revenue by 2030, anchored by its PASCAL, EVOQUE, and Sapien M3 technologies. The plan sits alongside updated Medicare coverage that could enable 100 to 200 additional U.S. centers to perform TAVR procedures, reinforcing the company's transcatheter ecosystem. Edwards' broader narrative projects $8.5 billion in revenue and $2.2 billion in earnings by 2029, requiring 9.3% yearly revenue growth and an earnings increase of about $1.2 billion from $979.9 million today. Three fair value estimates from the Simply Wall St Community cluster between US$91.47 and US$100.96 per share, against a $100.96 fair value that implies 14% upside to the current price. The company still faces risks around margins, tariffs, and competitive pressure in international markets.

Medtronic raised the lower end of its fiscal 2027 profit forecast and lifted its revenue growth outlook, citing strong demand for heart devices used in complex cardiovascular procedures. The Ireland-based company raised the lower end of its adjusted per-share profit forecast to $5.94 from $5.90 while keeping the upper end at $6.00, against an analyst average of $5.95, and now expects annual organic revenue growth of 7.25% to 7.75%, up from 6.75% to 7.25% previously. First-quarter fiscal 2027 revenue reached $9.756 billion, up 13.7% both reported and organically, beating the $9.55 billion analyst consensus, with adjusted earnings per share of $1.45 topping the $1.39 estimate. Growth was broad-based across segments, with Cardiovascular revenue up 19.5%, Diabetes up 16.9%, Neuroscience up 10.3%, and Medical Surgical up 10.0%, though Medtronic said about $570 million of the quarter's growth came from an extra week in the reporting period. The guidance still includes the diabetes business, which Medtronic has said it may fully separate before fiscal year-end, though CFO Thierry Pieton said the company is not under pressure to rush that timeline.

Bayer announced that the FDA has approved a label expansion for its kidney disease drug Kerendia, also known as finerenone, to treat adults with chronic kidney disease associated with type one diabetes. The drug, a selective non-steroidal mineralocorticoid receptor antagonist, was initially approved in the United States in 2021 for chronic kidney disease associated with type two diabetes, and its label was expanded in 2025 to include adults with symptomatic chronic heart failure with a left ventricular ejection fraction of at least 40 percent. This latest approval, the drug's third in the United States, follows a Priority Review designation and is supported by positive results from the pivotal phase three FINE-ONE study, in which Kerendia added to standard of care produced a statistically significant 25 percent reduction from baseline in the urine albumin-to-creatinine ratio over six months compared with placebo. The company said the expanded indication addresses an important unmet need, as approximately 30 percent of people with type one diabetes in the United States develop chronic kidney disease. Kerendia, marketed as Firialta in some countries, is approved for chronic kidney disease associated with type two diabetes in China, Europe and Japan, and finerenone is also approved for heart failure with a left ventricular ejection fraction of at least 40 percent in Europe, Japan, China and several other markets. Year to date, Bayer's shares have risen 29.8 percent compared with the industry's 10.9 percent growth, and sales of Kerendia skyrocketed 82.9 percent in the second quarter.

AstraZeneca shares rose 2.16% intraday after J.P. Morgan reiterated an Overweight rating, citing six Phase III readouts due in 2027 that together carry more than $10 billion in risk-adjusted peak sales and should improve confidence in the company's ability to keep growing beyond 2030. For laroprovstat, an oral PCSK9 inhibitor reading out in the first quarter of 2027, the bank models peak risk-adjusted sales of $3.2 billion against consensus of $2.4 billion, noting the drug showed a smaller LDL-C reduction than Merck's Lipfendra in earlier testing but carries no fasting requirement, which J.P. Morgan sees as the more important difference. On the bank's numbers, zibotentan with Farxiga in kidney disease gets an 80% probability of success on comparable earlier results, while balcinerenone with Farxiga in heart failure gets 50% because its partial mineralocorticoid receptor antagonism could dilute the benefit rivals have shown. In oncology, Datroway in triple-negative breast cancer and puxi-sam in endometrial cancer both carry 80%, and saruparib in prostate cancer is judged strong enough in the 30% of trial patients with HRR mutations to de-risk $3 billion of peak sales.

Eli Lilly reported second quarter revenue of $22.97 billion, up 47.7% year over year, while Merck posted $16.6 billion, up 5%, according to results from both drugmakers. Lilly's growth was driven by Mounjaro at $9.94 billion, up 91%, and Zepbound at $4.93 billion, up 46%, and the company raised its full-year guidance to $85 to $87 billion with an 85.8% gross margin. Merck's KEYTRUDA family brought in $8.4 billion, growing just 4%, and management said U.S. KEYTRUDA growth will moderate as the drug reaches peak penetration, while a $5.7 billion Terns acquisition charge pushed the company to a reported loss. Lilly's pipeline advanced with retatrutide showing weight loss approaching bariatric surgery levels in Phase 3, orforglipron, branded Foundeo, becoming the first once-daily oral GLP-1 with prescriber counts jumping from roughly 8,000 to 36,000 in one quarter, and FDA clearance of Mounjaro for cardiovascular risk reduction in type 2 diabetes on August 28. Merck is leaning on new launches including Lipvendra, the first oral PCSK9 inhibitor, and WINREVAIR, which grew 75% to $588 million, though GARDASIL China stayed weak and three Phase 3 oncology trials missed. Lilly trades at a forward P/E of 24 versus Merck at 15 with a 2.29% yield.

Hengrui Medicine announced that its subsidiary Guangdong Hengrui has received the Drug Clinical Trial Approval Notice for Recaticimab Injection issued by the National Medical Products Administration, approving the product to proceed with a Phase III clinical trial. The indication sought is for adult patients with intracranial atherosclerotic stenosis, to reduce the risk of stroke recurrence. Recaticimab Injection is a self-developed anti-PCSK9 monoclonal antibody that inhibits the binding of PCSK9 to LDL receptors, increasing the number of LDL receptors available to clear low-density lipoprotein from the blood, thereby lowering LDL cholesterol levels. The announcement shows that the product was approved for marketing in China in 2025 for adult patients with hypercholesterolemia and mixed dyslipidemia. Cumulative R&D investment in this project is approximately 422 million yuan.

Roivant Sciences shares surged 18% on September 8 after the biotech reported positive topline Phase 2 results for mosliciguat, an experimental treatment for pulmonary hypertension. In the PHocus trial, the drug produced a 56.3% placebo-adjusted reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with interstitial lung disease, well above the 20% threshold Leerink Partners analyst David Risinger had flagged as an important benchmark, along with a 35.2-meter placebo-adjusted improvement in six-minute walk distance at Week 16. Risinger said mosliciguat could potentially generate more than $10 billion in annual sales across multiple indications, a distinction that matters for Roivant's long-term growth strategy as it seeks to reduce reliance on a small number of products; Roivant has already secured U.S. approval for Lisraya. The company still must complete its Phase 3 PHrontier trial and show the benefits can be reproduced, and a disappointing late-stage result could trigger a significant valuation reset after the sharp post-results rally. Hedge fund holdings in Roivant rose to 64 in the second quarter from 60 in the first, though positioning was mixed, with QVT Financial cutting its exposure by 6% to approximately $839.6 million and Farallon Capital raising its stake by 48% to approximately $506.4 million.

Merck & Co. reported second-quarter worldwide sales of $16.6 billion, with its oncology franchise led by intravenous Keytruda and the subcutaneous formulation Keytruda QLEX generating $8.4 billion in quarterly revenue. The pulmonary arterial hypertension treatment Winrevair surged 75% to reach $588 million, and management raised its full-year 2026 sales guidance to a range between $66.3 billion and $67.3 billion. The company faces the loss of exclusivity for Keytruda toward the end of 2028, pushing it to fund and acquire new pipeline assets, including a personalized mRNA cancer vaccine collaboration with Moderna. According to Insider Monkey's database, 101 hedge funds held a stake in the company during the second quarter, up from 98 in the prior quarter, while short interest sits at just 0.99% of the float. Fisher Asset Management maintained the top position with 38.5 million shares, increasing its holdings by 46%.