Phentermine Hydrochloride/Topiramate

同写意20岁庆！第五届全球生物医药前沿技术大会报名开启！“意”同创新，穿越周期。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！GLP-1药物带来的“泼天富贵”终于轮到安进了。5月3日，这家巨头股价创下2009年以来单日最大涨幅，市值一夜增加约200亿美元。投资者的热情，源自一项II期临床的中期数据。安进CEO Robert Bradway透露，经内部审查，他们对肥胖症管线AMG133的“差异化特征”“充满信心”。尽管他并没有言明具体情况，但并不妨碍外界翘首以盼。正如在诺和诺德、礼来案例上体现的，一项研究能创造富可敌国的神话，背后则是掀起的一场制药革命。4年前，诺和诺德开展的大型临床试验显示，semaglutide帮助肥胖症患者平均减轻约15%的体重。该数据远超既往其他疗法所能达到的效果，很快引起研发热潮，重塑了肥胖症药物领域。目前，诺和诺德在9个国家以Wegovy的商品名销售semaglutide减肥疗法，产能已经落后于夸张激增的需求。在不少医生看来，Wegovy和其他同类药物是治疗肥胖症及相关问题的有效方案。分析师预测，到2030年，这些药物的年销售额将超过1000亿美元。制药商正在投资数十亿美元，试图在这个市场分一杯羹，探索调节新陈代谢和促进减肥的新方法。根据IQIVA最近的一份报告，约有120种治疗肥胖症的药物处于临床开发，三分之一以上通过刺激肠道激素如GLP-1起作用。要想取得成功，这些竞品至少要达到与Wegovy和Zepbound类似的减肥效果——Zepbound是礼来开发的一款GLP-1R/GIPR双重激动剂，去年获得FDA批准用于肥胖症。在最高剂量下，Zepbound使三分之一的患者体重减轻25%。而新型减肥药的热度正在外溢。该需求不仅兴盛于欧美国家，也引起了中国等市场的波动。券商预计，到2033年，中国的GLP-1产品市场规模将达到114亿美元，本地药企有望占据五分之一。那么，谁会成为牌桌上的下一波赢家？随着药企近期披露的动态，答案已经在路上。1时势英雄很长一段时间里，医生能开具的肥胖症药物寥寥无几。代表性的元老产品，是一种拟交感神经兴奋剂芬特明，于1959年首次获得批准。本世纪初的研究热潮，促使2012年和2014年又有三种疗法上市：Qsymia、Belviq和Contrave。这些药物在测试中显示出优于安慰剂的减肥效果，但很大程度上被认为并不出众，因此使用量有限。尤其是Qsymia，饱受安全性质疑，包括胎儿中毒风险和心脏问题。而同类产品Belviq，也因与癌症发病率升高的相关风险而在2020年被撤回。Qsymia等减肥药物的上市，正值第一批治疗糖尿病的GLP-1药物崭露头角之时。诺和诺德观察到降糖药Victoza的减肥效果后，在2014年底推出一种专门针对肥胖症的剂型Saxenda。虽然Saxenda对体重的影响不大，也从未广泛流行起来，诺和诺德却不打算放弃。很快，这家药企开发了另外的GLP-1产品。研究糖尿病药物Ozempic的同时，诺和诺德还尝试一种用于减肥的配方。重要的是，该公司着手实施一项长期计划，旨在证明减肥有助于保护心脏。两个赌注都得到了回报。一系列研究中，经过含有与Ozempic相同活性药物的Wegovy治疗，患者体重平均减轻了10%至16%，接近通常通过减肥手术达到的水平。另外，大规模的临床证明，与安慰剂相比，使用Wegovy减肥后，受试者的心脏病发作、中风或心血管死亡的相对风险降低了20%。2023年，该适应症获得FDA批准，Wegovy成为唯一一种可以在市场上宣传具有此类益处的减肥药。面对美国减肥治疗费用报销受限的情况，新标签无疑有助于Wegovy继续放量。可值得注意的是，礼来推出的Zepbound正显露不甘落后的势头。从表面上看，Zepbound在临床中的平均减重幅度更大——根据研究和剂量的不同，减重幅度在13%到21%之间。此外，与诺和诺德对Wegovy进行的测试相比，礼来的研究里更多试验组患者体重至少减轻了10%。现阶段，Zepbound和Wegovy还没有完整的“头对头”比较数据，因此无法就二者减肥功效得出明确结论。礼来的产品也尚未得到与它的竞争对手相媲美的心脏获益数据。一项名为SURPASS-CVOT的类似大型试验，将于2025年得出结果，意味着Zepbound大概会比Wegovy晚两年扩大自己的标签范围。Zepbound正与礼来开发的GLP-1药物Trulicity进行对比试验，以扩大其影响力。美国肥胖医学协会主席Angela Fitch表示，Zepbound很可能会显示出与Wegovy类似的对心脏的益处，“低剂量的GLP-1药物对心血管健康有积极影响”。2突围之路有目共睹，霸主的帝国版图已经初步成型。5月初，诺和诺德公布的财报显示，Wegovy第一季度的销售额便高达13.51亿美元。而去年11月刚获得批准的Zepbound，2024年首个季度也拿下5.17亿美元的成绩。通过Wegovy和Zepbound，诺和诺德、礼来已为减肥赛道设定了很高的标准，以至于一些业内人士将这些药物的获益形容为潜在竞品的“赌注”。后来者需要证明自己在疗效、安全性或便利性方面的优势。目前，市面上GLP-1减肥药物都是通过皮下注射给药（Wegovy治疗糖尿病患者已经有口服剂型），具有类似效果的口服剂性，可能会吸引那些不愿打针的群体。然而，作为多肽类药物，GLP-1产品一般很难通过消化道给药，因为它们在消化道中会被酶分解，而且由于体积相对较大，吸收速度很慢。另一种改进方向，可以针对现有产品的已知副作用。GLP-1药物常会引起恶心、呕吐等胃肠道问题。根据动物和生物标志物数据，还有人担心，此类药物与某些癌症相关。这可能使其他减肥机制更具吸引力，例如阻断大麻素或阿片受体。希望突破Wegovy和Zepbound统治版图的药企，还可尝试改进现有GLP-1药物被人体吸收和利用的方式。不论诺和诺德抑或礼来，尽管它们都致力于扩大产能，甚至直接买下收购工厂，也都很难生产出足够的减肥产品。而更容易被吸收的配方，则可以降低给药剂量，缓解产能压力。对商业化生产底子薄的Biotech，这不失为一条超车道。此外，药物研发人员正在研究如何保持肌肉量，因为目前的GLP-1药物会迅速减轻体重，导致肌肉组织减少。例如在FDA批准的一项试验中，患者使用Zepbound后肌肉量减少了11%。肌肉量的减少对老年人而言尤其令人担忧，体力下降可能会增加他们的虚弱程度。如果人们在体重大幅下降后又恢复，那么随后增加的往往是不成比例的脂肪。肌肉在新陈代谢中同样发挥着重要作用。既往资料显示，肌肉在静止状态下比脂肪组织燃烧更多能量，并分泌一种刺激葡萄糖吸收的激素。Biohaven负责临床开发的副总裁Peter Ackerman表示，他们“倾向于把肌肉看成是一个马达——它把东西从一个地方移动到另一个地方”。该公司正在开发一种针对肥胖症和罕见疾病脊髓性肌肉萎缩症的增肌药物。“我认为（肌肉）它在我们的整体健康中还有许多更重要的作用。”Ackerman说。2月，在增肌方面表现不错的BioAge Labs，完成了1.7亿美元的D轮融资。而此前，礼来已与其达成合作。去年7月，礼来还以近20亿美元收购了另一家开发增肌药物的公司Versanis。3千帆竞发礼来、诺和诺德的目标是保持目前在市场上的占有率。两家公司都在测试几种实验性减肥药物，旨在是推出口服版本，或是比现有产品更有效的治疗方法。诺和诺德已接近完成一项Wegovy口服剂型的减重III期试验。此外，该公司将Wegovy与cagrilintide相结合的药物，目前也处于后期开发阶段。据了解，cagrilintide可作用于一种名为淀粉样蛋白的肠道激素。礼来有两种药物处于临床III期。其中一种名为orforglipron的口服GLP-1药物，即将在2025年获得关键数据。另一种名为retatrutide的注射药物，可刺激GLP-1、GIP和胰高血糖素，相关研究结果将于2026年对外公布。而在更早期，礼来储备了4款进入临床I期、II期的在研药物；相应的，诺和诺德则披露了5种。“礼来跟诺和诺和覆盖了所有方面。”Metsera CEO Clive Meanwell认为，“这将是一个组合游戏，在不同的临床场景、市场中进行混合、匹配。”眼下，这家初创Biotech手握两款减肥药物。大大小小的制药商急于测试GLP-1竞品，这意味着，临床试验数据很快就能证明哪种方法最有效。一些公司已经被迫做出调整。例如，辉瑞开发了两种靶向GLP-1的非肽类口服药物，但结果好坏参半：有一种因安全性问题被放弃，另一种仍在测试中，但由于胃肠道副作用发生率较高，辉瑞正在重新调整剂量。Viking Therapeutics的运气较好。这家Biotech报告了其正在开发的一种GIP/GLP-1双靶点资产VK2735的早期数据。该药物既可以注射，也可以口服，似乎比Wegovy或Zepound更容易耐受。VK2735的II期研究预计将于今年晚些时候开始。与此同时，Viking的估值已飙升至80亿美元左右，暗示了投资者将其视为那些希望建立自己的产品管线的大型制药商的收购目标。其他MNC确实有所行动了。勃林格殷格翰就跟Zealand Pharma达成合作，开发了同时靶向GLP-1和胰高血糖素的survodutide，也取得令人鼓舞的早期疗效。III期临床的数据可能会在2025年底公布。投资者还在密切关注安进的两款药物，AMG133和AMG786。AMG133可以激活GLP-1，就像Wegovy和Zepbound一样，但又能阻断GIP——与Zepbound的机制相反。5月财报电话会议上，安进高官表示，AMG133有望在年内获得II期完整数据，随后进入III期临床。当被投资者请求置评，礼来并没有显得多被动。该公司声称同行的数据非常少，仍需要观望，而他们有自己的节奏。除了礼来，再生元、Biohaven同样在探索保持肌肉的减重方法，其结果将揭示该策略的作用有多大。美国本土之外，例如日本，大药厂盐野义、初创公司Kallyope、Skye Bioscience也都跃跃欲试。其中，盐野义正研究一种参与膳食脂肪吸收的酶的抑制剂，而Kallyope的药物则以肠道蛋白为目标，这些蛋白本身会刺激GLP-1等激素。Skye在测试一种药物，目的是通过阻断神经系统中的某些蛋白质来调节食欲。4鏖战中国GLP-1药物朝着千亿市场跑去。按照Bloomberg的预测，2030年，该类药物的全球市场就会超过超过1000亿美元。而中国市场，渐渐成为减肥药企的一块必争之地。近期，日本最大的证券公司Nomura发布分析报告。在它看来，中国GLP-1市场会以每年23%的速度增长，到2033年会达到114亿美元。届时，凭借具有竞争力的价格、庞大的销售网络以及潜在的更好功效，中国公司有望占据20%的份额。但这一切的前提是，以GLP-1为代表的本土减肥药能够成功上市。2023年6月，华东医药打响了第一枪。作为GLP-1生物类似药，该公司旗下的利拉鲁肽获得NMPA批准，用于需要长期体重管理的成人患者，作为低热量饮食和增加运动的辅助治疗。紧随其后，仁会生物自研的GLP-1药物贝那鲁肽，成功拿到了减重适应症。当时的公告称，该药是全球首款全人源GLP-1受体激动剂，与人体天然GLP-1氨基酸序列100%相同，抗体发生率低，疗效显著，安全性更佳。不过，二者都尚未披露具体的销售表现。至于其他在研竞品，尤其是多靶点策略方面，本土药企的探索也持续活跃。其中，信达生物的GLP-1R/GCGR双重激动剂玛仕度肽已于2月提交了相关上市申请，有望夺得“首个国产双靶点减重药”之名。根据既往数据，在以中国人群为主开展的临床研究中，接受治疗48周后，玛仕度肽可使患者体重下降18.6%，这个程度甚至高于礼来的Zepbound、诺和诺德的Wegovy。长于销售、推广的恒瑞医药，也在加速冲刺。5月，其GLP-1R/GIPR双重激动剂HRS9531已启动治疗肥胖的III期临床，如果进展顺利，预计将于2025年7月完成研究。三靶点激动剂方面，华东医药子公司道尔生物开发的FGF21R/GCGR/GLP-1R三重激动剂DR10624，已完成中国I期单次给药剂量递增研究，并在新西兰开展肥胖合并高甘油三酯血症的Ib/IIa期临床，预计2024年底前完成。另外，联邦制药也储备了一款长效GLP-1/GIP/GCG受体激动剂UBT251，已获得NMPA、FDA批准开展超重或肥胖等临床研究。最近更新进度的本土药企，是去年6月刚登陆港股的来凯医药。5月13日，该Biotech表示，自研ActRIIA单抗——增肌减重新药——LAE102的临床申请已获NMPA批准，公司正加速I期临床试验准备工作，即将启动肥胖症受试者招募。很明显，这些国产药物都存在长短不等的商业化时间窗。而与之相对应的是，海外巨头并未停下扩大市场的步伐。3月，诺和诺德表示，Wegovy预计今年在中国上市。欧洲市值第一的名头，并未让诺和诺德知足。相反，它正计划斥资5.56亿美元，以扩建其1994年开设的天津工厂，这是继2023年初向该工厂投资1.64亿美元后的又一布局。礼来也在摩拳擦掌。2023年8月，Zepbound用于成人长期体重管理适应症的上市申请被NMPA受理。几乎没有悬念，这家即将成为万亿美元市值巨头的药企，还会在中国的减肥市场占据第一梯队。问题在于，本土药企的成本或者营销优势，能在多大程度上对冲MNC的跑马圈地窗口期？或许，这很快会从信达生物等第一批抢滩者身上显露出来。主要参考资料：1.Amgen Stock Is Having Its Best Day Since 2009. Why Wall Street Is Excited About Its Weight-Loss Drug.，Barron's2.Amgen shares soar as executives outline obesity drug push；BioPharma Dive3.Chasing Novo and Lilly: The obesity drugs that could challenge Wegovy and Zepbound；BioPharma Dive’s4.Chinese pharma to ride on the global GLP-1 drugs bonanza；Nomura5.Riding GLP-1 wave, Novo Nordisk lays out $560M to boost drug production in China；Fierce Pharma6.中国GLP-1类“减肥”新药3期临床试验一览；医药观澜更多优质内容，欢迎关注↓↓↓

One study can start a pharmaceutical revolution.Four years ago, a large clinical trial run by Novo Nordisk showed a drug called semaglutide helped people with obesity lose, on average, around 15% of their weight. The results far exceeded what prior studies of other treatments had suggested was possible pharmaceutically, sparking a rush to research that has quickly reshaped the obesity drug field.Demand for semaglutide, now sold in nine countries by Novo as Wegovy, has surged to such heights the company cant keep up. Physicians see Wegovy and other drugs like it as powerful treatments for obesity as well as its many related health consequences.Analysts forecast annual sales of this new class of medicines to surpass $100 billion by early next decade. Drugmakers are investing billions of dollars in an attempt to get a piece of that market, as would-be competitors test new ways to regulate metabolism and spur weight loss.Some 120 drugs are now in clinical development for obesity, according to a recent report from Iqvia, from Wegovy mimics to psilocybin and coated glucose beads. More than one-third work by stimulating gut hormones like GLP-1 the target of Wegovy.To succeed, theyll likely have to at least match the double-digit weight loss numbers shown in testing for Wegovy and Zepbound, a rival drug from Eli Lilly approved in the U.S. last year. Heres where the field stands:How well do current drugs work?Until the early 2010s, physicians had only a few drugs they could prescribe for obesity, one of which, phentermine, was first approved in 1959. A spurt of research in the early 2000s led to the 2012 and 2014 approvals of three more treatments: Qsymia, Belviq and Contrave.While those drugs showed greater weight loss than placebo in testing, their effects were largely seen as unexceptional, resulting in limited uptake. Qsymia in particular was linked with safety issues, including the risk of fetal toxicity and heart problems. Belviq, meanwhile, was withdrawn in 2020 due to an association with higher rates of cancer.Their launches came around the time the the first GLP-1 drugs arrived on the market for diabetes. Novo, after seeing the weight loss effects of its diabetes drug Victoza, developed a daily injectable version specifically for obesity. Dubbed Saxenda, it had only a modest impact on weight and never caught on widely, either.Novo was quick to advance successor GLP-1s, however. While working on the weekly injection that became the diabetes drug Ozempic, Novo simultaneously studied a formulation for weight loss. Importantly, the company also committed to a longer-term plan designed to prove the expected weight loss benefit would help protect the heart.Both bets paid off. Treatment with Wegovy, which contains the same active drug as Ozempic, reduced weight by an average of 10% to 16% across a range of studies approaching levels typically achieved via bariatric surgery.A large study, meanwhile, proved weight loss from Wegovy reduced the relative risk of heart attacks, strokes or cardiovascular death by 20%, compared to a placebo. U.S. approval for this use last year made Wegovy the only weight loss drug that can be marketed as having such benefits. The new label helped push Medicare, which is prohibited by law from reimbursing for obesity treatment, into covering Wegovy for some people.Yet Lilly may ultimately have an upper hand with its rival drug Zepbound. On a surface-level comparison, Zepbound led to greater average weight loss in testing, showing reductions between 13% and 21%, depending on the study and dose. Additionally, a larger share of participants in Lillys studies experienced at least 10% weight loss than did participants in Novos testing of Wegovy.The two medicines have never been compared head to head in a trial, however, so no definitive conclusion can be drawn about their relative weight loss benefits.Lilly doesnt have heart data to match Novo yet. A similarly large Zepbound trial, called SURPASS-CVOT, should produce data in 2025, potentially putting an expanded label for the drug two years behind Wegovy. Lilly is testing Zepbound against an active medicine, its older GLP-1 drug Trulicity, however, which could strengthen its case.Zepbound is likely to show a similar heart benefit to Wegovy, according to Angela Fitch, president of the Obesity Medical Association and chief medical officer at the Massachusetts clinic Knownwell.Theres been a positive effect on cardiovascular health from the less potent GLP-1s, she noted.What could new drugs improve upon?Novo and Lilly have set the bar high with Wegovy and Zepbound, so much so that some in the industry are describing those drugs benefits as table stakes for would-be rivals. Competitors will need to show an advantage in efficacy, safety or convenience.Current GLP-1 drugs for weight loss are delivered via an under-the-skin injection. (Although Novo does sell an oral version of Wegovy for diabetes.) A pill with similar potency could be attractive to people whod prefer to avoid needles. However, peptide-based drugs like GLP-1s are difficult to deliver through the digestive tract, where they are broken down by enzymes and absorbed only slowly due to their relatively large size.Key GLP-1 and related drugs in developmentCompanyDrugStatusTypeKey datesEli LillyZepboundMarketedGLP-1/GIP agonistLate 2024 heart outcomes data readoutEli LillyorforglipronPhase 3Oral GLP-1 agonist2025 data readoutsEli LillyretatrutidePhase 3GLP-1/GIP/Glucagon agonist2026 data readoutsNovo NordiskOral semaglutidePhase 3GLP-1 agonist2024 FDA filing, adtl. data readoutsNovo Nordiskcagrilintide/semaglutidePhase 3GLP-1/amylin agonistLate 2024/2025 data readoutBoehringer / ZealandsurvodutidePhase 3GLP-1/glucagon agonistLate 2025 data readoutPfizerdanuglipronPhase 2Oral GLP-1 agonist2024 data on once-daily versionAmgenmaridebart cafraglutidePhase 2GLP-1 agonist, GIP antagonistLate 2024 data readoutViking TherapeuticsVK2735Phase 1/2GLP-1 agonist2024 oral Phase 2 trial startRocheRG 6641 (CT-868)Phase 2GLP-1/GIP agonist2024 data readoutRocheRG 6640 (CT-388)Phase 1GLP-1/GIP agonist2024 data readoutRocheRG 6652 (CT-996)Phase 1GLP-1 agonist2024 data readoutSOURCE: Company disclosuresAnother approach could target the drugs known side effects. GLP-1s are often associated with gastrointestinal problems such as nausea and vomiting. There are also concerns, based on an animal and biomarker data, of a possible link to certain types of cancer. This could make other proposed mechanisms for stimulating weight loss, such as blocking cannabinoid or opioid receptors, more attractive.Companies hoping to make inroads on Wegovy and Zepbound might also try to improve on how readily existing GLP-1s are absorbed and used by the body. Both Novo and Lilly have had difficulty manufacturing enough of the drugs, and a formulation thats more easily taken up by the body could allow for lower doses.Drug developers are looking, too, at how to preserve lean mass, as the rapid weight loss from current GLP-1s also leads to unwanted reduction in muscle tissue. Patients taking Zepbound lost 11% of their muscle mass in a substudy of a major trial that led to its FDA approval, for example.Shrinking muscle mass is particularly concerning for older people for whom less strength could increase frailty. And if people regain weight after significant losses, the subsequent gains tend to be disproportionately fat.Lean mass also plays an important role in metabolism, as muscles burn more energy at rest than fatty tissue and secrete a hormone that spurs glucose uptake.We tend to think of a muscle as a motor it moves things from one place to another, said Peter Ackerman, vice president for clinical development at Biohaven, which is developing a muscle-building drug in both obesity and the rare disease spinal muscular atrophy. I think it has many more important roles to play in our overall health.Whats next?Lilly and Novo aim to maintain their current hold on the market. Both companies are testing several experimental drugs with the goal of launching oral versions or even more effective treatments than their current products.Novo is already close to completing a Phase 3 trial program testing an oral form of Wegovy. It also has in late-stage development a combination of Wegovy with a compound called cagrilintide that acts on a gut hormone called amylin.Lilly has two drugs in Phase 3: an oral GLP-1 dubbed orforglipron that is approaching key data readouts next year and an injectable treatment called retatrutide that stimulates GLP-1, GIP and a third hormone known as glucagon. Results in obesity are due in 2026.Lilly has four experimental drugs in Phase 1 or 2, while Novo has five.[Lilly and Novo] cover all the bases, said Clive Meanwell, CEO of Metsera, a newly launched startup that has two obesity drugs in clinical testing. Our belief is it's going to be a portfolio play, with mix and match, with different clinical circumstances and different markets.Select non-GLP1 drugs in clinical developmentCompanyDrug(s)StatusTypeKey datesEli LillybimagrumabPhase 2activin inhibitor2024 data readoutNovo NordiskINV-202Phase 2CB1 inhibitor2025 data readoutShionogiS-309309Phase 2MGAT2 inhibitor2024 data readoutKallyopeK-757, K-833Phase 2Nutrient receptor agonist2024 data readoutAmgenAMG 786Phase 1UnknownMid-2024 data readoutRegenerontrevogrumab, garetosmabPhase 1myostatin, activin A inhibitorsMid-2024 Phase 2 trial startBiohaventaldefgrobep alfaPhase 1myostatin inhibitor2024 Phase 2 trial startSkye BiosciencenimacimabPhase 1CB1 inhibitorMid-2024 Phase 2 trial startSOURCE: Company disclosuresThe rush by drugmakers large and small to test GLP-1 rivals means clinical trial data could soon prove which approaches work best.Already, some companies have been forced to adjust. For example, Pfizer developed two non-peptide oral drugs targeting GLP-1, but both returned mixed results. One was scrapped because of safety concerns. The other remains in testing, but Pfizer is reworking its dosing because of a high rate of gastrointestinal side effects.Viking Therapeutics has had better luck. The biotech reported encouraging early data for a GIP-GLP1 combination its developing as both a shot and a pill. The drug appears more tolerable than Wegovy or Zepound.A Phase 2 trial of the pill is expected to begin later this year. In the meantime, Vikings valuation has swelled to around $8 billion, suggesting investors see it as an acquisition target for larger drugmakers looking to build their pipeline.Zealand Pharma and Boehringer Ingelheim, meanwhile, are partnered on a drug called survodutide that targets GLP-1 and glucagon and has also produced encouraging early results. Phase 3 study data could come late next year.Investors are also watching closely two drugs from Amgen called AMG 133 and AMG 786. The first activates GLP-1, like Wegovy and Zepbound, but blocks another hormone called GIP opposite of Zepbounds mechanism.The big biotech hasnt disclosed exactly how AMG 786 works.Regeneron Pharmaceuticals, Biohaven and Lilly are exploring treatments designed to preserve lean mass, results from which could reveal how much this strategy might contribute.Further afield are companies like Japans Shionogi and startups Kallyope and Skye Bioscience. The former drugmaker is working on an inhibitor of an enzyme involved in dietary fat absorption, while Kallyopes drugs target gut proteins that themselves stimulate hormones like GLP-1. Skye is testing a drug designed to regulate appetite by blocking certain proteins in the nervous system. '