10 clinical trials to watch in the first half of 2022 (2023)

Ben Fiedler chief editor

Increase UC 12

PfizersArena was acquired for $7 billion, one of the industry's biggest acquisitions of 2021, built largely on the promise of a single drug called etrasimod. After disappointing sales of the weight-loss drug, Arena has repositioned itself around the drug that has shown promise in several inflammatory diseases. Etrasimod works the same way as Zeposia, once Celgene's crown jewelGet a receiptNow sold by Bristol Myers Squibb.

Pfizer bet on Arena because it believed its drug was better and did so before major clinical trial results confirmed that belief -- surprising some Wall Street analysts. Those results will be published this year, starting with two trials testing Etrimod in ulcerative colitis.

Pfizer executives announced in a recent conference call that they reviewed blinded data from two studies, Elevate 12 and Elevate 52, and assumed etrasimod would be a commercial success. (Increase 12 results may be available first, according to the federal clinical trials database.)

Pfizer is counting on such results to boost its inflammatory disease business, which includes the drugs Xeljanz and abrocitinibSlowed down due to security concerns.

VAT 008

The coronavirus pandemic has changed since 2020, when Sanofi and GlaxoSmithKline jointly developed a vaccine for COVID-19. The original strain of the coronavirus has given way to elusive variants that pose more difficult targets for vaccines being developed by companies such as Moderna, partners Pfizer and BioNTech. At the same time, booster vaccines are becoming increasingly important as they have proven to be the best defense against rapidly spreading Omicron variants and weakened immune protection.

These factors make Sanofi and GlaxoSmithKline attractive for potential roles in vaccine trials in 2022 and beyond, which have now been delayed several times. In December, the couple reported his shootingIt can significantly increase the concentration of antiviral antibodiesAmong people previously vaccinated with any of the four most commonly used vaccines. But they can't apply for approval until they show their vaccine can prevent COVID-19 in a large clinical trial -- a trial that's harder to do as more people get vaccinated or become infected.

Sanofi and GSK are expected to announce their results in early 2022. If the results are positive, their vaccine is based on proven technology and may help where other vaccines are not widely available.

graduation 1

Can Aduhelm, the first new Alzheimer's drug in decades, really slow the mental and physical decline caused by the disease? Doctors, experts, and even FDA reviewers disagree.spark a conversationThat made the agency's decision to approve the drug one of the most controversial in its history.

In the face of conflicting clinical trial data, the FDA decided to approve Aduhelm based on its mode of action, creating a long-standing and unproven disease hypothesis. Later in 2022, results from Roche and Eisai could provide evidence for Aduhelm, its maker, Biogen and the FDA, or further challenge the drug's approval.

Aduhelm, Roche's gantenerumab and Eisai's lecanemab work by targeting protein clumps in the brain called amyloid. Over the past decade, clinical trials have failed due to a long line of precursors that somehow also target amyloid.

Beyond that, however, gantenerumab and lecanemab could show benefit, depending on the type of amyloid clumps targeted and more carefully tailored study designs. (Gantenerumab performed poorly in a previous study, but is being reevaluated at a higher dose.)

Eisai - Biogen's development partner for Aduhelm - hasApply for expedited approvalBased on preliminary data from the study, lecanemab showed that the treatment can clear amyloid in the brain. Meanwhile, Roche recently told the study's researchers that it would not seek fast-track approval for its drug.

Phase 3 data from the two companies is not expected until the second half of the year, although a Roche study is being announcedgraduation 1– Designation in the federal database for clinical trials was completed in May. In any case, these studies will be closely monitored throughout the year.

Meanwhile, Eli could quickly follow Lilly Roche and Eisai into a Phase 3 lead for Alzheimer's drug donanemab by mid-2023. Also the drug companyApply for expedited approvalBased on the amyloid reduction data, the FDA is expected to make a decision by the end of 2022.

NCT04853368

Gradually, Vertex Pharmaceuticals has blocked potential competitors for four of its key cystic fibrosis drugs, which now bring in nearly $7 billion a year. But biotech's toughest test may yet lie ahead.

Earlier this year, AbbVie was set to announce evidence-based results of a triple-drug combination with ingredients similar to Trikafta, Vertex's CF triplet and its best-selling drug. The program is part of AbbVie's long-term effort to challenge Vertex CF's leadership position. The pharmaceutical giant partnered 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 as some of the drugs had disappointed early results. The teacher was surprised.

But AbbVie has since worked to improve its drug mix, making changes to two of its three ingredients. Jeff Stewart, chief commercial officer, said in a conference call earlier this year that the company would like to see an "efficiency advantage" over the Trikafts, even a small one. Although AbbVie doesn't expect full results until late 2022, the company will announce some results publicly in the first quarter. Data fromTwo-drug planThe same is expected.

The results have important implications for Vertex as the company struggles to build a business beyond cystic fibrosis.contrite.

TROPiCS-02

Gilead has invested over a decade and billions to become a major player in oncology, with mixed results. The company has won approval for three cancer drugs in the past four years, but sales are falling from its established HIV drugs.

Cancer drug Trodelvy aims to help change the narrative of Gilead, the number one reason for the biotech$21 billion was spentIn 2020, the drug's manufacturer, Immunomedics, was created.

Currently, Trodelvy is only approved for the treatment of advanced triple-negative breast cancer and a form of bladder cancer. For the drug to be the blockbuster that Gilead envisioned, Trodelvy must be successful in an ongoing Phase 3 trial called TROPiCS-02.

The study will compare Trodelvy with different types of chemotherapy in patients with HR-positive, HER2-negative breast cancer, which accounts for 60 to 70% of all breast cancer cases. Patients in the study experienced disease progression despite two to four prior treatments, including a relatively new breast cancer drug called a CDK 4/6 inhibitor.

Positive results in the first quarter of 2022 will be critical for Gilead. A win would give Trodelvy a $2 billion revenue opportunity, increase Gilead's stake by 5% to 8% and confirm the Immunomedics deal, wrote RBC Capital Markets analyst Brian Abrahams.

Emergency-2

Developing new drugs to treat mental illness is notoriously difficult, so any promising drug is subject to intense scrutiny. A good example is the drug KarXT developed by Karuna Therapeutics. Exciting Results from the Phase 2 Schizophrenia TrialHe increased the company's capitalization by billionsAnd it is one of the most talked about drugs in this field.

KarXT combines the powerful antipsychotic xanomeline with a chemical called trospium, which is said to reduce potentially problematic side effects such as sedation and vomiting. Because of these problems, Eli Lilly developed and discontinued Xanomeline in the 1990s. But Karuna's drug showed few of these signs in interim trials, but had a measurable impact on schizophrenia symptoms.

This supports a reevaluation of xanomeline and other similar drugs that act on proteins in the nervous system called muscarinic receptors. A similar drug from Cerevel Therapeutics also shows promise. Karuna has since initiated further studies of KarXT, including a phase 2 study in Alzheimer's patients with psychosis.

Stifel analysts estimate that muscarinic drugs will be worth about $4 billion in the treatment of schizophrenia. So there's a lot to be said for Karuna's phase 3 trial called EMERGENT-2, which is expected to have results by mid-year. However, many promising neurological drugs have so far underperformed in late-stage trials, often due to an unexpectedly large placebo effect.

Reproduction

Few biotechs have rallied faster than Intercept Pharmaceuticals, whose shares plummeted from more than $400 a share to less than $16 a share because of the turmoil surrounding opicholic acid, a drug used to treat fatty liver disease. NASH disease.

Intercept Support promotes early clinical outcomesPhase 3 of the REGENERATE study has been a clear successIn 2019, the company was positioned to commercialize the first treatment for NASH, a disease believed to affect millions of people in the United States. However, the FDA does not believe that the benefits outweigh the potential risks, which include cardiometabolic effects. the institutionAsk the Intercept for more dataFrom efforts leading to long delays,corporate restructuringand several senior executives resigned.

But the interception still has a chance to recover. Potential rivals such as Gilead, Genfit and NGM Biopharmaceuticals failed to capitalize on Intercept's mistake as NASH proved a tougher target than previously expected. Others, such as Madrigal Pharmaceuticals, are still awaiting Phase 3 results.

If REGENERATE's updated results are positive, Intercept could receive its first NASH drug approval. The results earlier this year are expected to include more safety data than Intercept's initial filing, as well as analysis of 18 months of liver biopsies from more than 500 patients.

Recent results will also be available from REVERSE, a study that enrolled NASH patients with liver cirrhosis but no symptoms yet. The overall data set should provide "long-awaited clarity on the viability of [obeticholic acid] in NASH," SVB Leerink analyst Thomas Smith wrote recently.

Alpha-2

The past year has been a challenging one for the field of so-called standard CAR-T therapies. It is well known that allogeneic therapy aims to be a more convenient alternative to the personalized cell therapies currently used to fight a variety of blood cancers. However, it has not yet been shown to be less resistant to more complex treatments. The biggest surprise, however, came in October when the FDAAllogenee Therapeutics clinical trial suspended, one of the leading companies in this field.

The move comes after researchers discovered a "chromosomal abnormality" in a patient treated with ALLO-501a, an approach adopted by Allogene to advance the lymphoma treatment. Although the clinical significance of this finding is unclear, the agency responded decisively by halting not only trials of ALLO-501a, but all of Allogene's other programs.

Since then, Allogene has been working with the FDA to determine whether gene editing was to blame in the preparation of its treatment. The company, in turn, downplayed the incident, and executives expressed surprise at the FDA's actions.

But the clinical lockdown nearly halved Allogene's share price and raised new questions about the standard treatment. Several analysts believe this year's results and the resumption of trials could have broad implications for allogeneic and other developers of standard cell therapies, many of which involve gene editing.

NCT04886596,Renoir

The COVID-19 vaccine has garnered global attention over the past two years, becoming one of the most widely used and most profitable products in the history of the pharmaceutical industry. Fewer headlines reported a high-stakes race to develop a vaccine against another common and potentially deadly respiratory syncytial virus infection. Important clinical trial results are expected this year.

RSV is known to cause about 177,000 hospitalizations in older adults and 58,000 hospitalizations in children under five each year. The virus has proved a difficult target for pharmacists: efforts to develop a vaccine dating back to the 1960s have been unsuccessful. The only way to fight the infection is with antiviral therapy. Synthetic antibodies can also be used to prevent the diseases they cause.

That may change soon. GlaxoSmithKline, Pfizer and Johnson & Johnson have developed vaccines that train the body to recognize the viral proteins that RSV uses to infect human cells. All three vaccines are currently in late-stage trials. Pfizer and GlaxoSmithKline are expected to have preliminary Phase 3 data by mid-year, with J&J soon after.

The economic implications of these studies are significant. Cowen analysts predict that the RSV vaccine market will be worth nearly $10 billion by 2028.

Apollo-B

One of the most surprising trial failures of 2021 occurred in the final week of a drug for transthyretin amyloidosis, a rare genetic condition that affects the heart.Not superior to placebo in phase 3 studyNeil Kumar, chief executive of drug developer BridgeBio, said in a statement that the results were "confusing", with shares falling nearly 80%. They are raising levels in the Alnylam Pharmaceuticals study, which is expected to provide data by mid-2022.

Alnylam's Onpattro was the first RNA interference drug to hit the market when the FDA approved it in 2018 for neurological damage associated with amyloid transthyretin (ATTR). Alnylam has since won approval for a number of other RNAi drugs, but Onpattro remains the best-selling drug. Key to its development was the demonstration that Onpattro could help ATTR patients with heart disease - a more rapidly progressive, deadlier and more common disease.

The APOLLO-B study was designed to do just that, and Alnylam has provided encouraging early results from the study. This year, Alnylam will report whether Onpattro can help patients outperform placebo in a trial measuring how far they can walk in six minutes after a year of treatment. This is the same benchmark that BridgeBio's drug failed, largely because placebo recipients did significantly better than in previous ATTR trials.

BridgeBio said it does not yet know why its drug is in short supply. But Alnylam shares fell more than 15 percent amid fears that the bar for success in the ATTR study may now be higher, Stifel analyst Paul Matteis said. Matteis wrote that Alnylam believes its drug should have a stronger effect because it works differently than similar drugs approved by BridgeBio and Pfizer.