After 55 new drug approvals at the FDA last year, biopharma and the U.S. agency are still going all guns blazing in getting new therapies out to patients. But what are the most hotly tipped—and potentially most lucrative—approvals on the horizon for 2022? Well, there’s a real eclectic mix of targets here, from Alzheimer’s disease and diabetes to psoriasis and lung cancer. And, according to the life sciences data crunchers at Evaluate Vantage, the top 10 most anticipated drugs are set to make a collective $26.9 billion by the middle of the decade. It’s Eli Lilly’s year in 2022, with the top two biggest prospects belonging to the Big Pharma and taking nearly half that total with just shy of $11 billion in potential earnings from its prospective drugs in Alzheimer’s and diabetes, respectively. Overall, it’s the Alzheimer's drug prospects that dominate the sales charts as a group, with Lilly’s donanemab worth potentially $6 billion by 2026 and Roche’s rival gantenerumab set to take $2.5 billion. That’s $8.5 billion in total potential in a disease area that hadn't produced a new therapy for nearly two decades. But with Biogen’s ongoing woes with Aduhelm—which also had sky-high expectations last year but has faced what could be the worst launch in drug history—the Lilly and Roche predictions may be some of the riskiest we’ve seen in many years. It’s also a good launch year for Bristol Myers Squibb, which, like Lilly, has two drugs in the top 10. Its hopefuls mavacamten in cardiomyopathy and deucravacitinib in psoriasis and autoimmune disorders are together worth $4 billion in predicted peak sales. But it’s not been an easy path to 2022 for all of the top 10: Johnson & Johnson and Legend Biotech were hit by an extended FDA review that pushed an expected decision from November to late February over manufacturing and technical concerns. And mavacamten had its own FDA delay to contend with. And, while Alzheimer's drugs may be the riskiest proposition launch-wise, Reata Pharmaceuticals is at the highest risk of falling short of an approval. An FDA advisory committee unanimously rejected its kidney disease hopeful bardoxolone last year, putting its projected $2.2 billion in 2026 sales in serious jeopardy. Check out the top 10 most anticipated drug launches of the year below. 1. Donanemab Drug: Donanemab Company: Eli Lilly Used for: Alzheimer's disease Est. 2026 sales: $6 billion It’s a case of déjà vu for the most hotly anticipated drug launches of the year as, once again, it’s an Alzheimer’s disease drug that leads Evaluate Vantage’s highest-grossing potential list. Last year, that honor went to Biogen’s amyloid therapy aducanumab, which was approved in June as Aduhelm. Evaluate had forecast peak sales for that drug at around $4.8 billion in 2026. This year, it’s Eli Lilly’s turn to take the top spot, with Evaluate eyeing a beefier $6 billion in sales for its Alzheimer’s hopeful donanemab. Like Aduhelm, donanemab is also an anti-amyloid beta monoclonal antibody, but Lilly hopes to best its rival and thus gain greater market share. These are big figures, but there's also plenty of room for doubt that the drugs using this approach to fight Alzheimer's—and that includes No. 3 on our list, another Alzheimer's hopeful from Roche—can actually measure up to these estimates. Biogen, in fact, only made $300,000 from Aduhelm in the third quarter of 2021. And there's a reason for that: An FDA advisory panel originally rejected the drug, which has questionable efficacy and fresh safety concerns, but the agency granted an accelerated approval based on biomarker evidence. Biogen also priced the drug very high, at $56,000, before slashing the sticker price in half at the end of last year. It’s had possibly one of the worst drug launches in history, with a number of physicians and medical groups questioning its worth and refusing to prescribe it. As Biogen's biomarker evidence showed, the drug can clear sticky proteins, known as amyloid, that can clog the brain. It is believed that amyloid plaques could be an underlying cause of Alzheimer's, though this has not been directly proven, and the theory has seen many drugs fail in the past. It also remains an open question as to whether clearing it can actually help reduce Alzheimer’s symptoms. But the FDA, in approving Aduhelm, set a precedent that clearing amyloid is an acceptable bar for getting an Alzheimer's drug on the market. Hence, after nearly two decades of no new drugs for the disease, Roche, Lilly and other drugmakers have suddenly jumped back into action. Lilly is not going in with blind optimism. Mindful of Biogen’s woes, the Big Pharma decided last year to run a head-to-head clinical trial for donanemab against Aduhelm. Analysts from Evercore ISI see donanemab as reducing amyloid more than other similar drugs—including Aduhelm—which could give it a market edge. In comparing the data on Lilly's drug to Aduhelm's, the Evercore ISI team saw an advantage for donanemab—and figured those data gave Lilly confidence to run the head-to-head test. Comparing different trials is always full of caveats, but, if Lilly can prove this thesis, it will be a major win for the pharma. In preparation for donanemab's potential launch, Lilly is already working to build out its commercial capabilities in neuroscience, Lilly’s Chief Commercial Officer Anat Ashkenazi told Fierce Pharma recently. With the donanemab launch in mind, the company split its Bio-Medicines business into two units last July, one focused specifically on neuroscience. Lilly has submitted the drug for an accelerated approval and expects to complete its rolling submission by the end of the first quarter. If all goes to plan at the FDA, the company aims to launch donanemab toward the end of the year. Donanemab is also slated to have results from a confirmatory trial by 2023, three years ahead of Biogen, which isn’t expecting data from its confirmatory trial until 2026. Lilly says it expects limited sales when the drug first hits the scene, but the arrival of phase 3 data in 2023 could serve as another “inflection point” for the drug, Ashkenazi said. By the middle of next year, Lilly expects to have data from that head-to-head trial against Aduhelm as well. Should donanemab gain the green light, Lilly will, however, likely still come up against some of the same issues that have been plaguing Biogen. It may gain approval, but in the real world, it will still need to be priced competitively and show it can actually help patients if it wants to hit that $6 billion sales figure. 2. Tirzepatide Drug: Tirzepatide Company: Eli Lilly Used for: Diabetes Est. 2026 sales: $4.9 billion Eli Lilly landed a one-two punch on our most anticipated drug launch list this year. Its Alzheimer’s disease asset donanemab took the top spot with $6 billion in estimated sales by 2026, and it’s also taking second place with its diabetes hopeful tirzepatide, which Evaluate Vantage reckons could be bringing in $4.9 billion by the middle of the decade. This is much firmer market territory for Lilly compared to Alzheimer’s, given its long history in diabetes. And, like much of its competitive life in this disease, it’s going head-to-head against Danish rival Novo Nordisk. Tirzepatide works as a dual GIP and GLP-1 agonist and has been acing trials left and right over the past few years, helping Type 2 diabetes patients keep their blood sugar levels and weight down. It’s biggest win came last year when it beat Novo Nordisk’s GLP-1 blockbuster, Ozempic, in a direct head-to-head study. In the phase 3 SURPASS-2 trial, the readout was clear: In terms of reducing blood sugar levels and body weight, Lilly’s drug at all three doses tested was better than Novo’s GLP-1 drug at its highest approved dose. As analysts noted at the time, however, the differences between the two drugs were not huge, but the size of tirzepatide’s benefit over Novo’s entrenched Ozempic could make all the difference. “I still question usage of a dual agonist if efficacy is only slightly better,” Bernstein analyst Wimal Kapadi told Fierce Pharma last March when the head-to-head data first came out. In his investor note, fellow Bernstein analyst Ronny Gal said tirzepatide’s edge was “likely not sufficient to drive the transformation of the GLP-1 market,” so Lilly will need to work hard to win over this skepticism. Ozempic already makes around $3.4 billion a year and is set to reach a peak of about $8 billion. It has racked up more indications since its initial approval, including obesity, where it is marketed as Wegovy. Lilly, however, is going all in. The pharma already has a sizable diabetes commercial team in place thanks to its repertoire of insulins plus GLP-1 and SGLT2 meds Trulicity and Jardiance, respectively. And, while the company expects a diabetes indication first, it’s also eyeing a potential use in obesity to challenge Wegovy. Data for its obesity drive will be out in April. At the recent J.P. Morgan Healthcare Conference, Lilly CEO Dave Ricks said the company was mulling the idea of splitting the branding of tirzepatide into diabetes and obesity, as Novo had done, and marketing the pair separately. 3. Gantenerumab Drug: Gantenerumab Company: Roche Used for: Alzheimer's disease Est. 2026 sales: $2.5 billion Alzheimer’s disease (AD) is making a comeback after a long research drought. While Eli Lilly takes the top spot for sales potential with its AD hopeful, donanemab, which could bring in $6 billion in 2026, Roche takes the final podium position with its rival drug gantenerumab. Sales for the drug, which has a similar mechanism to Lilly’s as an anti-amyloid beta monoclonal antibody, aren’t expected to reach the heights of donanemab. Evaluate Vantage sees it bringing in less than half of its potential rival, at $2.5 billion by 2026. This would still be a good haul of blockbuster cash for the Swiss major, however, as it would help the company expand beyond its oncology staple and move more deeplyinto central nervous system disorders. But, as with all AD drugs—and, in fact, CNS research in general—with great sales potential comes great risks, and gantenerumab has already endured a rocky path through development. Roche, in fact, put the drug on the shelf in 2014 after it failed a phase 3 study but revived it in 2018, with the company saying it suspected a higher dose could spur an effect. A second Washington University School of Medicine study of the candidate failed as well. So, whether gantenerumab can build the clinical data needed to back up an approval remains to be seen. Genentech is working on a number of phase 3 studies, and executives including Rachelle Doody, M.D., Ph.D., global head of neurodegeneration and franchise head in product development, told Fierce Biotech last year that they remain focused on that task rather than on how Biogen’s activities around controversially approved Aduhelm might affect their regulatory prospects. 4. Deucravacitinib Drug: Deucravacitinib Company: Bristol Myers Squibb Used for: Psoriasis Est. 2026 sales: $2.4 billion With deucravacitinib, Bristol Myers Squibb took on an opportunity cost in losing out on Otezla; this year, industry watchers will start to see whether that bet could pay off. When faced with an antitrust roadblock for its $74 billion megamerger with Celgene in 2019, BMS chose to keep experimental deucravacitinib and offload growing blockbuster Otezla to Amgen for $13.4 billion. Despite their different mechanisms, the U.S. Federal Trade Commission thought the two meds’ oral dosing—in an inflammatory disease market filled with injectables—raised an anti-competition red flag. Phase 3 results backed BMS’ decision in that binary choice: Deucravacitinib topped Otezla, helping more patients with moderate to severe plaque psoriasis achieve skin clearance in the POETYK PSO-1 and POETYK PSO-2 trials. The FDA is expected to rule on deucravacitinib’s use in that indication by Sept. 10. BMS has been billing deucravacitinib as the potential new oral of choice in psoriasis, with expansion opportunities in psoriatic arthritis and inflammatory bowel diseases. The company has pegged the drug to possibly reach over $4 billion in peak sales, while Evaluate Vantage in its 2022 preview report put its 2026 sales estimate at $2.4 billion. In the first nine months of 2021, Otezla—first approved in the U.S. in 2014—brought in global sales of $1.62 billion. Deucravacitinib may be able to shake Otezla’s leader status as an oral option, but injectables are a different story. The proportion of patients who achieved at least 75% skin symptom relief as measured by the psoriasis area severity index looked smaller in the two BMS phase 3 trials than newer injectables like Novartis’ Cosentyx, Eli Lilly’s Taltz and AbbVie’s Skyrizi achieved in their studies. The FDA might also make commercial life difficult for deucravacitinib. The agency recently slapped classwide safety warnings on oral JAK inhibitors about increased risks of cancer and heart-related events and limited their use to after a patient has tried existing meds. Deucravacitinib’s target, TYK2, is a member of the JAK family. If the FDA paints deucravacitinib with the same brush, it would hurt the drug’s opportunity as a front-line treatment. BMS' argument for deucravacitinib centers around it being a first-in-class drug with a different mechanism than other JAK drugs. The med hasn’t shown any of the concerning side effects linked to JAK inhibitors—such as low blood platelet count, abnormal cholesterol levels or liver dysfunction—in its clinical trials up to one year, BMS Chief Medical Officer Samit Hirawat, M.D., noted in a recent interview with Fierce Pharma. But, as Amgen commercial chief Murdo Gordon noted in an investor call in April 2021, it took a yearslong large-scale postmarketing study of Pfizer’s Xeljanz to really understand the safety problems of that JAK med. That means BMS might need longer-term data to fully convince doctors of deucravacitinib’s safety profile. Until then, the TYK2 inhibitor will likely be first used in patients who fail on Otezla, which is about a third of the Otezla-treated population, Amgen management told SVB Leerink during a recent event, analyst Geoffrey Porges said in a December note. Beyond plaque psoriasis, deucravacitinib recently hit a snag in ulcerative colitis when a phase 2 trial failed to meet its primary and key secondary goals. BMS is now taking a second shot at the indication with deucravacitinib at a higher dose. In psoriatic arthritis, the company is running two phase 3 trials in moderate to severe disease, with Otezla once again in its crosshairs. itial data from the studies are expected in 2024. 5. Bardoxolone Drug: Bardoxolone Company: Reata Pharmaceuticals Used for: Chronic kidney disease in Alport syndrome Est. 2026 sales: $2.2 billion The FDA is slated to decide the fate of Reata Pharmaceuticals' chronic kidney disease (CKD) drug bardoxolone Feb. 25. If approved, it would be the first therapy for Alport syndrome patients, a disease that damages the tiny blood vessels in the kidneys and can lead to kidney disease and renal failure. There’s $2.2 billion in peak sales on the line, but the likelihood of approval for the rare indication took a major hit last year when an expert review body for the FDA unanimously knocked down the drug for approval. Reata's stock sank more than 60% during that week of the Dec. 8 decision. The FDA doesn’t have to follow its advisory committee’s decision. For example, a year ago, the agency went against the panel's rejection of Biogen's Alzheimer's disease med Aduhelm and gave it an approval. Nonetheless, such a reversal remains a rarity. The committee for bardoxolone said Reata did not prove the therapy was effective in slowing the progression of CKD in Alport syndrome patients. The experts noted that the drug's benefits did not outweigh its risks based on the data Reata submitted. While bardoxolone achieved its primary and key secondary goals in its phase 3 registrational trial dubbed CARDINAL, the agency's review team questioned whether the drug actually reduced CKD progression. The expert reviewers specifically wanted an explanation on why Reata used eGFR—an estimate of the kidney’s filtration rate—as the main measure for CKD in its phase 3 trial given other measures might have been better able to show efficacy. Based on the eGFR measure, Reata said patients treated with bardoxolone experienced a statistically significant improvement in kidney function compared to patients treated with placebo. But the FDA reviewers didn’t agree that this proved efficacy. Panelist Paul Palevsky, M.D., who is chief of the kidney medicine section at the VA Pittsburgh Healthcare System, summed up the dissent: “[I am] quite concerned that the data provided does not meet the bar of showing this will slow the time to end-stage kidney disease,” he said at the meeting in December. Reata said after the 13-0 rejection that it planned to provide additional information and data leading up to decision day, including potential data from non-Alport studies. It has not publicly announced any new results since then. Bardoxolone is currently in a 550-patient late-stage trial in patients with autosomal dominant polycystic kidney disease and in a 70-patient midstage study in people with CKD at meaningful risk of progression to end-stage kidney disease. The drug has a long development history. In 2010, Reata linked up with AbbVie in deals totaling more than $800 million. In 2012, a data monitoring committee found patients with CKD in a phase 3 study had a higher rate of heart-related side effects. In response, Reata halted the trial, eliminated half its workforce and returned to the drawing board. In 2014, Reata moved the drug into a midstage study in pulmonary arterial hypertension. In 2017, it began trials in Alport, but, two years later, AbbVie walked away from its pact with the company. Reata paid $75 million to regain the rights to its drug, while AbbVie would no longer be eligible to royalties from bardoxolone sales. 6. Tezepelumab-ekko Drug: Tezspire (tezepelumab-ekko) Companies: AstraZeneca and Amgen Used for: Asthma Est. 2026 sales: $2 billion AstraZeneca and Amgen got the party started early, nabbing an approval in December 2021 ahead of schedule and launching tezepelumab-ekko, now branded as Tezspire, in mid-January 2022 for certain forms of asthma. As an add-on maintenance treatment, the monoclonal antibody has a chance to challenge the dominance of Regeneron and Sanofi’s blockbuster Dupixent, because it has shown effectiveness across a broad range of patients with the severe form of the lung disease. Among the 339 million people worldwide with asthma, 10% have the severe version the drug is targeting. Amgen said at the recent J.P. Morgan Healthcare Conference that it is eyeing a market of about 1.3 million patients with uncontrolled asthma in the U.S. alone. Use of the therapy will likely begin with the low eosinophilic population, which currently does not have a biologic treatment option. Analysts at SVB Leerink predict Tezspire can nab about 30% of the uncontrolled asthma population within that group of patients. Uptake could, however, be slow initially, because the drug is launching during the omicron surge and also carries a high price, analysts warn. But it’s still slated to reach a peak of $2 billion: The drug's list price comes in at $47,229, a full $10,000 higher than Dupixent when it was launched in 2017. The companies are also trialing the therapy in several other indications—including chronic rhinosinusitis with nasal polyps—which together could eventually take a bite out of Dupixent’s market dominance. Dupixent, which made $4 billion in 2020, is indicated to treat moderate to severe atopic dermatitis and also as a maintenance treatment for chronic rhinosinusitis with nasal polyposis. In 2018, it grabbed an FDA nod as a maintenance treatment for moderate to severe eosinophilic, oral steroid-dependent asthma in patients whose condition is not controlled with their current asthma medicines. One big plus for Tezspire in its comparison to the Dupixent in the asthma setting is its label: While Dupixent’s says the drug does not show benefit in patients with low levels of eosinophils, there is no such qualifier for Tezspire, which can thus edge in on this market. In trials, Tezspire indeed showed success in helping a subgroup with low levels of eosinophil white blood cells. Existing asthma drugs such Dupixent and AstraZeneca’s older asthma drug Fasenra target eosinophilic forms of the disease. Patients with non-eosinophilic disease have limited treatment options. The tezepelumab collaboration agreement between Amgen and AstraZeneca began in 2012 and was updated in 2020, with both agreeing to share costs and profits equally after a milestone payment paid to Amgen. AstraZeneca, which brings expertise in respiratory diseases, is leading the development process, while Amgen, with a proven name in biologic drugs, is handling the manufacturing and is also joining forces on the marketing side. Last year, in anticipation of the approval, Amgen and AstraZeneca launched an unbranded awareness website for asthma, “Break the Cycle,” which features E! host Nina Parker. AstraZeneca said it will have more marketing campaigns but is already tapping medical influencers on Instagram and running ads on TikTok to help spread its awareness campaign. Sanofi and Regeneron are of course spending big on marketing Dupixent, leading the TV spend list for last year by plowing $288 million to take the crown. 7. Vutrisiran Drug: Vutrisiran Company: Alnylam Used for: Amyloid transthyretin amyloidosis Est. 2026 sales: $1.8 billion Alnylam may already have a marketed therapy for amyloid transthyretin (ATTR) amyloidosis, but a newer candidate could give it an edge in its competition with Pfizer. Vutrisiran is Alnylam’s follow-on candidate to its ATTR amyloidosis drug Onpattro. The marketed therapy is given as an infusion every three weeks, which makes vutrisiran’s less cumbersome proposed under-the-skin dosing every three months more attractive. Evaluate Vantage projected the new med could reach $1.8 billion in 2026 sales, and an approval decision is expected April 14. As its predecessor does, vutrisiran is targeting a hereditary form of ATTR amyloidosis called polyneuropathy (PN), which affects the nerves. About 50,000 patients live with hereditary ATTR worldwide. Both are RNA interference therapies that target TTR mRNA to reduce disease-causing TTR protein deposits in tissues. In the phase 3 HELIOS-A study, vutrisiran data were better than results from the placebo group of an earlier Onpattro trial called APOLLO. On the primary endpoint of nine-month change in a measure called modified neuropathy impairment score that evaluates neurologic problems, patients on vutrisiran showed a 2.2-point improvement, while the placebo group deteriorated by 14.8 points. In addition, vutrisiran also nailed key secondary measures including patient-reported quality of life and a 10-meter walk test Although the primary endpoint pitted vutrisiran against placebo in a different trial, the HELIOS-A trial did also have an Onpattro arm. There, the older therapy led to a a 1.4-point improvement. While vutrisiran looks on track to secure an FDA nod in PN, another form of ATTR called cardiomyopathy (CM), which causes heart problems, represents a much larger market. Most ATTR-CM cases are the result of aging-related destabilization of TTR, while some others inherit the condition from a parent. Nonhereditary ATTR is estimated to affect 200,000 to 300,000 people worldwide, according to Alnylam. Thanks to an FDA approval in ATTR-CM in 2019, Pfizer’s Vyndaqel/Vyndamax has enjoyed enviable growth. In the first nine months of 2021, the once-daily oral med sold $1.45 billion globally, a 69% increase year over year. The drug isn’t approved in ATTR-PN in the U.S. All eyes are on Onpattro’s Apollo-B trial to gauge the strength of Alnylam’s RNAi approach in the more prevalent ATTR-CM disease. The company expects to have those data mid-2022. Vutrisiran’s own ATTR-CM trial, dubbed HELIOS-B, is further out. A recent competitor’s failure gave Alnylam some bittersweet feelings. In a surprising revelation, BridgeBio found its TTR stabilizer acoramidis failed to beat placebo on a six-minute walk test in ATTR-CM patients. Industry watchers had hoped for better results than Pfizer’s Vyndaqel/Vyndamax showed. The fact that patients in the placebo arm barely declined on the walk test marks a baffling departure from what was seen in Pfizer’s ATTR-ACT trial along with prior natural history data, Stifel analysts wrote in a December note. As BridgeBio noted, the decline in walking distance in its ATTRibute-CM trial’s placebo group was more than 70% lower than the decline observed in ATTR-ACT’s treatment group. Removing a potential rival from the equation could have meant a big relief for Alnylam, but, as the Stifel team noted, if BridgeBio’s well-performing placebo arm is really the “new standard,” the hurdle for success for Onpattro in APOLLO-B could be higher, given that trial also uses the six-minute walk test as its primary outcome measurement. For vutrisiran’s HELIOS-B, though, Alnylam has set clinical improvement—specifically, a composite of death and recurrent cardiovascular events—as the primary target, while the six-minute walk test is a secondary endpoint. Alnylam’s founding CEO John Maraganore, Ph.D., won’t be steering the wheel for vutrisiran’s launch. The longtime chief executive has handed the reins to Yvonne Greenstreet, who was the company’s president and chief operating officer. Elsewhere in the ATTR arena, Ionis’ Tegsedi also holds a small market share, and AstraZeneca just paid $200 million upfront for the company’s follow-on med eplontersen, which is currently in phase 3 testing. The British pharma also recently in-licensed an early-stage asset from Neurimmune. That drug, dubbed NI006, is an antibody targeted at misfolded amyloid conformation. 8. Mavacamten Drug: Mavacamten Company: Bristol Myers Squibb Used for: Hypertrophic cardiomyopathy Est. 2026 sales: $1.7 billion Mavacamten, the centerpiece of Bristol Myers Squibb’s $13.1 billion acquisition of MyoKardia in 2020, will likely start its commercial journey this year. BMS CEO Giovanni Caforio said from the outset that the drug’s potential as a first-in-class therapy that addresses the underlying cause of obstructive hypertrophic cardiomyopathy (HCM) justified the purchase price, not to mention additional opportunity in the less common nonobstructive form of the disease. For BMS, mavacamten could be the company’s next big cardiovascular asset when Pfizer-shared blood thinner Eliquis, currently BMS’ top-selling drug, falls off the patent cliff in the latter half of the decade. BMS figures mavacamten could reach over $4 billion in nonrisk-adjusted revenues in 2029. Evaluate Vantage, for its part, projected $1.7 billion for the drug’s 2026 sales in a 2022 preview report. Mavacamten seemed on track to get an FDA decision in symptomatic obstructive HCM in January, but the agency in November postponed the deadline by three months, as the agency needed more time to work out a safety monitoring program, known as a Risk Evaluation and Mitigation Strategy, according to BMS. The BMS filing included such a program, which is usually set up for drugs with important side effect concerns. The drug’s phase 3 trial found that its safety and tolerability were similar to the placebo arm. HCM is the most common genetic heart disease, affecting about 1 in 500 people by BMS' estimate. It’s marked by increased thickening of heart muscle and hence harder contraction. Many cases are asymptomatic, while others can cause various problems as serious as sudden death. Existing treatments such as beta blockers only deal with symptoms. Mavacamten targets the underlying HCM disease by inhibiting cardiac myosin to reduce heart muscle contractility. Before the BMS buyout, MyoKardia had reported positive pivotal trial results in patients with symptomatic, obstructive HCM. In the phase 3 EXPLORER-HCM trial, 36.6% of patients on mavacamten responded and achieved meaningful improvements in oxygen consumption and heart function after 30 weeks, compared with 17.2% of those in the placebo group. BMS has followed up with more data showing the drug could improve patients’ perception of their health status and that it worked in patients who were also taking beta blockers. Competition is also brewing in HCM. Last year, Cytokinetics rolled out encouraging phase 2 data for its HCM contender, aficamten (previously known as CK-274). The med showed competitive results in terms of hitting a target resting gradient, a marker of heart pressure. The drug, with a newly earned FDA breakthrough designation in obstructive HCM, is heading to a phase 3 dubbed SEQUOIA-HCM. Meanwhile, BMS expects a 2022 readout from the phase 3 VALOR-HCM study, which is meant to expand mavacamten’s obstructive HCM label to include information on the drug’s ability to reduce the need for highly invasive septal reduction therapy in high-risk patients. The company also plans to start a phase 3 trial for nonobstructive HCM this year. And it recently launched a proof-of-concept phase 2 study in heart failure with preserved rejection fraction. 9. Cilta-cel Drug: Cilta-cel Companies: Johnson & Johnson and Legend Biotech Used for: Multiple myeloma Est. 2026 sales: $1.7 billion Chinese company Legend Biotech and U.S. partner Janssen, the R&D unit of Johnson & Johnson, were the darlings of the American Society for Clinical Oncology (ASCO) annual meeting a few years ago. Their CAR-T therapy known as cilta-cel wowed the crowd, and last year, it won a speedy review by the FDA for its use in multiple myeloma. Janssen and Legend swiftly set up a sales team and put marketing platforms in place, ready to jump into action as soon as that expected green light came in. But then, things took a left turn. In November last year, the FDA unexpectedly hit the brakes on its review, which was focused on the relapsed/refractory setting in multiple myeloma. The agency had questions about the BCMA-directed CAR-T therapy, specifically around nonclinical data and chemistry, manufacturing and controls. The original date set for its approval under its priority review was late November, but the FDA pushed its decision back to Feb. 28 this year. Analysts at the time, including Jefferies, remained confident of approval and saw little long-term impact on the companies as a result of the delay. And speaking at the recent J.P. Morgan Healthcare Conference, Legend CEO Ying Huang, Ph.D., was also still bullish about cita-cel’s prospects and chances of approval, adding that it was “ready to go” if the FDA says yes in February. Legend has ramped up its manufacturing base to avoid the supply pitfalls that has befallen some of its competitors. But there are a lot of competitors: GSK’s BCMA-targeted antibody-drug conjugate Blenrep for certain types of relapsed/refractory patients, approved in 2020, as well as Bristol Myers Squibb and bluebird bio’s CAR-T therapy Abecma, approved last March, are some of its more direct rivals in this space. Blenrep is expected to achieve $2 billion in peak sales and made 67 million pounds ($90 million) for GSK during last year's third quarter. Abecma, slated to make $1.9 billion in 2026, made $71 million in the third quarter of 2021. Also in the game are J&J's own Darzalex, Bristol’s Celgene-inherited Revlimid and Takeda’s proteasome inhibitor Velcade, all three of which bring in blockbuster sales. Takeda also has the follow-on drug Ninlaro, while Amgen has Kyprolis, which is also paired with Darzalex for myeloma patients who've already tried between one and three previous therapies. But J&J and Legend still believe they can carve out a good chunk of the relapsed/refractory multiple myeloma market with cilta-cel, and Evaluate Vantage sees $1.7 billion in sales by 2026 despite the FDA prolonging its decision. The pair is hoping to hit the ground running on the awareness front, too. Last year, it set up a specialized patient support program and a dedicated sales team, and J&J plans to roll out a customized program to help patients who receive cita-cel navigate the treatment journey. To help with this, J&J has set up Janssen Compass, which allows a single point of contact—a nurse—assigned to help bring the right resources to a patient to manage obstacles along the way, including access challenges and side effects. In Janssen Compass, this “care navigator” will help set expectations, educate each patient on how to manage potential obstacles and support them in developing a care plan to communicate with doctors. J&J has been using it for other drugs including Darzalex but is boosting its use for cita-cel to maximize use of the therapy. 10. Adagrasib Drug: Adagrasib Company: Mirati Therapeutics Used for: Non-small cell lung cancer Est. 2026 sales: $1.7 billion Rounding off our top 10 most anticipated drug launches for the year is Mirati Therapeutics with its Amgen-rivaling cancer hopeful adagrasib. Mirati is, in fact, already at the FDA’s doorstep for its first potential drugapproval and expects a decision in the coming months, with a launch ready to go for its blockbuster-in-waiting KRAS inhibitor. Adagrasib is Mirati’s attempt to catch up to Amgen, which beat Mirati to the punch. Last May, the Big Pharma won approval in the U.S. for its KRAS drug, Lumakras, for non-small cell lung cancer (NSCLC) with a particular genetic mutation called KRAS G12C. In the final weeks of 2021, Mirati asked the FDA to approve adagrasib in KRAS G12C patients as a single treatment in second-line NSCLC, new CEO David Meek said at the recent J.P Morgan Healthcare Conference. Lumkras itself is approved as a monotherapy and in the second-line setting. The drug booked $36 million in the third quarter, the first full quarter after it launched. It’s slated to make $1.3 billion by 2025, less than the $1.7 billion adagrasib is set to make a year later despite getting on the market 12 months after its rival—if it gets approved, of course. At the JPM conference, Mirati's CEO said the company has been working on building its commercialization team for the past two years. “Adagrasib is going to be a very big drug for a very long time,” Meek said. Why the bigger estimate for little Mirati? Undeterred by not being first, the biotech is already hard at work in the clinic to find an edge over Amgen, and that includes in indications outside NSCLC. At the European Society of Medical Oncology (ESMO) cancer conference last September, Mirati showed an early win in colorectal cancer (CRC) patients that trumped Amgen. Amgen linked Lumakras to an overall response rate (ORR) of just 7% in CRC, leading it last summer to drop work in CRC as a monotherapy. Meanwhile, data released at ESMO showed that the response rate in the 45 evaluable patients who received adagrasib as a single agent stood at 22%. The 10 patients listed as responders include one person with an unconfirmed partial response who remains on study. Absent that unconfirmed response, the ORR would be 20%. Median duration of response was 4.2 months. Mirati has said that an ORR of 20% and median duration of four months are the threshold to potentially seek accelerated approval of adagrasib. The data in the ESMO abstract put it over that bar—but only by a whisker. Amgen is, however, still pursuing CRC, but with help: Lumakras is in a phase 1/2 trial coupled with Amgen’s approved CRC drug Vectibix. But Mirati appeared to take another win just last month when adagrasib led to a 41% response rate in patients with pancreatic and other gastrointestinal tumors. This came from the phase 2 KRYSTAL-1 study that featured patients with cancers of the biliary tract, appendix, small bowel, gastro-esophageal junction or esophagus who have a mutation of the KRAS gene. Mirati disclosed the findings at the 2022 American Society for Clinical Oncology Gastrointestinal Cancers Symposium. A specific breakdown of adagrasib's impact shows the drug worked better in patients with pancreatic cancer than in those with other gastrointestinal tumors. Patients with pancreatic cancer notched a 50% objective response, whereas others with GI cancers achieved a 35% response. Patients responded for a median of 7 months and 7.9 months, respectively. The disease control rate was 100% across the 27 patients in the subset. Patients with pancreatic cancer did not see progression of their disease for a median of 6.6 months; for GI tumors, the duration was 7.9 months. While next year features the massive patent cliff for AbbVie's Humira, plenty of Big Pharma's significant brands are set to take the tumble in 2022. (Jan Vašek/Pixabay) With AbbVie’s megablockbuster Humira set to face an onslaught of biosimilars next year, industry watchers have long circled 2023 as the year of the major pharma patent cliff. But this year’s slate of top losses of exclusivity covers sizable brands worth more than $17 billion in annual sales. When Bristol Myers Squibb inked its $74 billion deal to buy Celgene back in early 2019, the timing of generics to blockbuster multiple myeloma drug Revlimid loomed as one major uncertainty for the deal. Now, the $12 billion brand is set to face some of its first copycats within weeks. It’s looking to be the industry’s biggest loss of exclusivity since Pfizer’s Lipitor, which peaked at $13 billion in annual sales. But, unfortunately for AbbVie, Revlimid will only hold that distinction for a year. AbbVie’s megabrand Humira, which generates around $20 billionannually, is set to tumble next year as a host of generics vie for market share. For BMS, the copycat pain won’t end there. The company also expects generics to its chemotherapy drug Abraxane, which pulled in $898 million in the U.S. last year starting in late March. Aside from BMS, AbbVie is losing U.S. exclusivity on a pair of eye drugs in 2022. Restasis, a drug inherited in its Allergan buyout, is facing new copycats from Viatris after that company’s FDA generic approval last month. And Combigan, another former Allergan med, is facing a key patent expiration in April.
10 clinical trials to watch in the first half of 2022
Biotech stocks ended 2021 in a slump. But positive study results in breast cancer, schizophrenia and Alzheimer's could help turn fortunes around.
One year ago, the biotechnology sector was in the middle of a record run. The successful development of coronavirus vaccines and drugs had helped slow the pandemic and propelled investment into new companies going public at a historic rate. Biotech stock indexes traded at all-time highs.
But that momentum quickly vanished. Clinical and regulatory setbacks, as well as the prospect of drug price reform in the U.S., weighed on companies large and small, driving down stock prices and opening a gulf between the industry's performance and the broader market's. Newly public biotechs struggled to keep their footing, with nearly 80% of the 2021 IPO class trading below their offering prices, according to data from BioPharma Dive.
Positive clinical trial results — events that companies can use to sway investors, cut deals and raise cash — could help turn things around. And multiple opportunities lie ahead, with key studies in breast cancer, cystic fibrosis and ulcerative colitis set to read out in the first half of the year.
Here are 10 to watch:
Company: Pfizer, Arena Pharmaceuticals Disease: Ulcerative colitis Treatment type: Small molecule Trial: Elevate UC 12 Why it's important: Pfizer's $7 billion buyout of Arena, one of the sector's largest acquisitions of 2021, was largely based on the promise of a single drug known as etrasimod. After a disappointing past selling an obesity drug, Arena had rebuilt itself around the medicine, which showed early promise in several inflammatory diseases. Etrasimod works the same way as Zeposia, once the crown jewel of Celgene's acquisition of Receptos and now sold by Bristol Myers Squibb. Pfizer gambled on Arena on the belief that its drug is better and did so — to the surprise of some Wall Street analysts — before key clinical trial results were available to potentially prove out that hypothesis. Those results will emerge this year, beginning with a pair of studies testing etrasimod in ulcerative colitis. Pfizer executives revealed on a recent conference call that they had already looked at blinded data from two studies, known as Elevate 12 and Elevate 52, and made the deal assuming etrasimod will succeed. (Results for Elevate 12 could be ready first, according to a federal clinical trials database). Pfizer is banking on such an outcome to boost its business treating inflammatory diseases, an area where its drugs Xeljanz and abrocitinib have been slowed by safety concerns.
Companies: Sanofi, GlaxoSmithKline Disease: COVID-19 Treatment type: Protein vaccine Trial: VAT008 Why it's important: The coronavirus pandemic has shifted since 2020, when Sanofi and GlaxoSmithKline partnered to develop a COVID-19 shot. The original coronavirus strain gave way to more elusive variants that are harder targets for the vaccines developed by Moderna, partners Pfizer and BioNTech and others. Boosters, meanwhile, have grown in importance, as they've proved the best defense against the fast-spreading omicron variant and the waning of vaccine protection. Those factors have left Sanofi and GSK, now several times delayed in their vaccine research, with a potential role to play in 2022 and beyond. In December, the two reported their shot can significantly boost levels of virus-fighting antibodies in people who had previously received any of the four most widely used vaccines. But they can't file for authorization until proving their vaccine can prevent COVID-19 in a large clinical trial, a test that has become harder to complete as more people are vaccinated or infected. Sanofi and GSK expect to report results from their study in early 2022. If positive, their vaccine, which relies on well-established technologies, could be helpful in places where other shots aren't widely available.
Company: Roche Disease: Alzheimer's Treatment type: Antibody Trials: Graduate 1 Why it's important: Does Aduhelm, the first new Alzheimer's drug in decades, actually slow the mental and physical deterioration caused by the disease? Doctors, experts and even the Food and Drug Administration's own reviewers haven't agreed, fueling a debate that's made the agency's decision to approve the drug among the most controversial in its history. Faced with conflicting clinical trial data, the FDA chose to clear Aduhelm based on how it is thought to work, elevating a long-debated and unproven disease hypothesis in the process. Over the course of 2022, study results from Roche and Eisai could offer supporting evidence for Aduhelm, its developer Biogen and the FDA, or throw the drug's approval further into doubt. Aduhelm, Roche's gantenerumab and Eisai's lecanemab all work by targeting clumps of a protein in the brain known as amyloid. A long list of predecessors — also aimed at amyloid, in one fashion or another — have failed in clinical trials over the past decade. Hopes are higher, though, that gantenerumab and lecanemab could show a benefit, based on the type of amyloid clump they target and more carefully tailored study designs. (Gantenerumab fell short in a previous study, but is being reevaluated at a higher dose.) Already, Eisai — Biogen's development partner on Aduhelm — has applied for accelerated approval of lecanemab based on mid-stage trial data showing treatment could eliminate amyloid in the brain. Roche, meanwhile, recently informed trial investigators it would not seek an expedited OK for its drug. Phase 3 data from both companies aren't expected until the second half of the year, although one of Roche's trials — dubbed Graduate 1 — is earmarked to be completed by May on a federal database of clinical trials. Either way, the studies will be closely tracked throughout the year. Eli Lilly, meanwhile, could quickly follow Roche and Eisai with Phase 3 data for its Alzheimer's drug donanemab by mid 2023. The pharma has also applied for accelerated approval based on amyloid-reduction data and expects an FDA decision toward the end of 2022.
Company: AbbVie Disease: Cystic fibrosis Treatment type: Small molecule Trial: NCT04853368 Why they're important: One by one, Vertex Pharmaceuticals has held off would-be competitors to its four dominant cystic fibrosis drugs, which now generate almost $7 billion each year. But the biotech's stiffest test may be just around the corner. Early this year, AbbVie is expected to disclose proof-of-concept results for a three-drug combination made of similar components as Trikafta, Vertex's own triplet for CF and its top-selling medicine. The program is part of a long-running effort by AbbVie to challenge Vertex's leadership in CF. The pharma giant worked with Galapagos NV for five years before deciding to acquire the Belgian biotech's cystic fibrosis portfolio in 2018, a move that surprised analysts at the time given the disappointing early results some of the drugs had produced. But AbbVie has since worked to improve the drug combination, making changes to two of its three components. The company is hoping to see "an efficacy advantage," even a small one, over Trikafta, chief commercial officer Jeff Stewart said on a conference call earlier this year. Though AbbVie isn't expecting full results until the end of 2022, it'll publicly disclose some findings in the first quarter. Separate data from a two-drug regimen are expected as well. The results have significant implications for Vertex, whose efforts to establish a business outside of cystic fibrosis have underwhelmed.
Company: Gilead Disease: Breast cancer Treatment type: Antibody-drug conjugate Trial: TROPiCS-02 Why it's important: Gilead has spent more than a decade and billions of dollars trying to become a major player in oncology, with mixed results. The company has won approvals of three cancer drugs in the last four years, but sales are dwarfed by the HIV medicines for which it's long been known. The cancer drug Trodelvy is meant to help change the narrative for Gilead, and is the key reason the biotech shelled out $21 billion for the medicine's developer, Immunomedics, in 2020. Currently, Trodelvy is only approved for late-line use in triple-negative breast cancer and a form of bladder cancer. For the drug to become the blockbuster medicine Gilead envisions, Trodelvy has to succeed in an ongoing Phase 3 study known as TROPiCS-02. The trial is testing Trodelvy against several chemotherapies in patients with HR-positive, HER2-negative breast cancer, a form of the disease accounting for 60% to 70% of all breast cancer cases. Patients in the study have seen their disease progress despite two to four prior treatments, among them a relatively new type of breast cancer drug known as a CDK 4/6 inhibitor. A positive result in the first quarter of 2022 is crucial for Gilead. Success would open up a $2 billion revenue opportunity for Trodelvy, add 5% to 8% to Gilead's shares and validate the Immunomedics deal, wrote Brian Abrahams, an analyst at RBC Capital Markets.
Company: Karuna Therapeutics Disease: Schizophrenia Treatment type: Small molecule Trial: EMERGENT-2 Why it's important: Developing new drugs for psychiatric disorders is notoriously difficult, which is why any medicine that shows promise draws close attention. KarXT, a drug developed by Karuna Therapeutics, is a good example. Compelling results in a Phase 2 schizophrenia study added billions of dollars to the company's market value and made it one of the field's most closely watched medicines. KarXT combines the powerful antipsychotic xanomeline and a chemical, trospium, that's meant to blunt its potentially problematic side effects like sedation and vomiting. Lilly developed and then shelved xanomeline in the 1990s because of those issues. But Karuna's drug showed few signs of them in mid-stage testing while producing a notable effect on schizophrenic symptoms. That's supported a reevaluation of xanomeline and other drugs like it, which act on nervous system proteins known as muscarinic receptors. A similar medicine from Cerevel Therapeutics has also shown promise. And Karuna has since launched additional studies for KarXT, among them a Phase 2 study in Alzheimer's patients with psychosis. Analysts at Stifel expect the muscarinic drug class to be worth about $4 billion in schizophrenia. A lot is therefore riding on Karuna's Phase 3 study, called EMERGENT-2 and expected to deliver results by the middle of the year. Many promising neurological drugs have fallen short in late-stage testing before, though, often because of higher-than-expected placebo effects.
Company: Intercept Pharmaceuticals Disease: Non-alcoholic steatohepatitis Treatment type: Small molecule Trial: REGENERATE Why it's important: Few biotechs have had a more dramatic rise and fall than Intercept Pharmaceuticals, shares of which have swung from more than $400 apiece to less than $16 during the tumultuous saga of obeticholic acid, its drug for a fatty liver disease known as NASH. Intercept backed up encouraging early clinical results with apparent success in the Phase 3 REGENERATE study in 2019, positioning the company to bring the first treatment to market for NASH, a disease thought to affect millions of people in the U.S. The Food and Drug Administration, however, wasn't convinced the benefits outweighed the potential risks, among them cardiometabolic side effects. The agency asked Intercept for more data from the trial, leading to a lengthy delay, a corporate restructuring and several senior executive departures. But Intercept still has a chance to rebound. Would-be rivals like Gilead, Genfit and NGM Biopharmaceuticals failed to capitalize on Intercept's stumbles as NASH proved a tougher target than previously expected. Others, such as Madrigal Pharmaceuticals, are still awaiting Phase 3 results. Intercept, then, could still win the first NASH drug approval if updated results from REGENERATE are positive. The results, which are expected early this year, will include substantially more safety data than were in Intercept's original filing, as well as 18-month liver biopsy analyses from 500 more patients. Late-stage results are also due from REVERSE, a study that enrolled NASH patients with cirrhosis but who haven't yet shown symptoms. The overall data set should provide "long-awaited clarity on the viability of [obeticholic acid] in NASH," Thomas Smith, an analyst at SVB Leerink, wrote recently.
Company: Allogene Therapeutics Disease: Large B-cell lymphoma Treatment type: Cell therapy Trial: ALPHA-2 Why it's important: This past year was challenging for the field of so-called off-the-shelf CAR-T therapy. Meant to be a more convenient alternative to the personalized cell treatments now used to fight several blood cancers, allogeneic treatments, as they're known, haven't yet proven as durable as their more complex counterparts. But the biggest surprise came in October, when the FDA suspended clinical studies run by Allogene Therapeutics, one of the field's leading companies. The move was made after researchers discovered a "chromosomal abnormality" in one patient treated with ALLO-501a, a lymphoma treatment Allogene had selected for advancement. Though the clinical significance of that finding isn't yet known, the agency responded firmly, halting testing of not just ALLO-501a, but all of Allogene's other programs as well. Since then, Allogene has been working with the FDA to understand whether the gene editing involved in preparing its treatment is to blame. For its part, the company has downplayed the event, with executives expressing surprise at the FDA's actions. Even so, the clinical hold nearly halved Allogene's share price and added new questions about off-the-shelf treatments. The results of the investigation and restart of testing, which multiple analysts expect this year, could have far-reaching implications for Allogene and other developers of off-the-shelf cell therapies, many of which involve gene editing.
Companies: GlaxoSmithKline, Pfizer Disease: Respiratory syncytial virus Treatment type: Vaccine Trials: NCT04886596, RENOIR Why they're important: Vaccines for COVID-19 have dominated the world's attention over the past two years, becoming some of the most widely used and lucrative products in the pharmaceutical industry's history. Fewer headlines have covered a high-stakes race to develop shots for another common and potentially deadly infection caused by respiratory syncytial virus. Important clinical trial results are expected this year. RSV, as it's more commonly known, causes an estimated 177,000 hospitalizations among older adults each year and 58,000 in children under five. The virus has proven a tough target for drugmakers: efforts dating back to the 1960s to develop a vaccine have been unsuccessful. The only way to combat infections is antiviral treatment; synthetic antibodies can also be used to prevent the disease they cause. That could soon change. GlaxoSmithKline, Pfizer and Johnson & Johnson have each developed shots that train the body to recognize a viral protein RSV uses to infect human cells. All three vaccines are now in late-stage testing, with Pfizer and GSK anticipating initial Phase 3 data by the middle of the year and J&J shortly afterwards. The financial implications for the studies are significant. Cowen analysts forecast the market for RSV vaccines will be worth nearly $10 billion by 2028.
BONUS: Company: Alnylam Pharmaceuticals Disease: ATTR cardiomyopathy Treatment type: RNA interference Trial: Apollo-B Why it's important: One of 2021's more surprising trial failures came during its final week, when a drug for a form of the rare genetic disease transthyretin amyloidosis that affects the heart didn't outperform placebo in a Phase 3 study. The results were "baffling," Neil Kumar, the CEO of the drug's developer, BridgeBio, said in an announcement that sent shares falling by nearly 80%. And they've raised the stakes for an Alnylam Pharmaceuticals study that should deliver data in the middle of 2022. Alnylam's Onpattro was the first RNA interference medicine to get to market when the FDA approved it in 2018 for the nerve damage associated with transthyretin amyloidosis, or ATTR. Alnylam has since won approvals of multiple other RNAi drugs, but Onpattro remains its top-seller. And one key to its growth is proving Onpattro can help ATTR patients with heart problems — a faster-moving, deadlier and more common form of the condition. The APOLLO-B study is meant to do just that, and Alnylam has produced encouraging early results from the trial. This year Alnylam will report whether Onpattro can help patients perform better than a placebo on a test of how far they can walk in six minutes after one year of treatment. That's the same measure on which BridgeBio's drug failed, largely because placebo recipients fared significantly better than they have in previous ATTR studies. BridgeBio says it doesn't yet know why its drug fell short. Nonetheless, Alnylam shares tumbled more than 15% on concerns that the bar for study success in ATTR may now be higher, according to Stifel analyst Paul Matteis. Alnylam, for its part, believes its drug should have a more potent effect because it works differently than BridgeBio's and a similar, approved medicine from Pfizer, Matteis wrote.