Oncology's research boom

Two years ago, a drug called Enhertu changed the way doctors thought about treating an aggressive form of breast cancer, making it important to know not only whether their patients’ tumors express a protein known as HER2, but how much.

New study results presented June 2 at the American Society of Clinical Oncology may further shift breast cancer care. The findings suggest Enhertu, a type of medicine called an antibody-drug conjugate, should be used before chemotherapy in a common type of advanced breast cancer. They may also usher in a new classification for breast tumors — those with “ultralow,” but still detectable, levels of HER2 protein.

The trial tested Enhertu against doctor’s choice of chemotherapy in 866 people with metastatic, hormone receptor-positive breast tumors that had either “low” or “ultralow” HER2 expression. Study participants had already received one hormone therapy and a type of drug called a CDK 4/6 inhibitor, or at least two prior hormone therapies.

Enhertu’s developers, AstraZeneca and Daiichi Sankyo, said in April the trial succeeded, but didn’t provide specifics. Trial data revealed at ASCO show Enhertu met its main objective by delaying cancer progression or death by a median of about 13 months, versus roughly eight months for those who received chemotherapy. That result translated to a 38% reduction in the risk of cancer progression for people who got Enhertu.

“That’s an attention-grabbing difference,” said Adrienne Waks, the associate director of breast oncology clinical research at Dana-Farber Cancer Institute. Waks wasn’t involved with the trial, but has served as an adviser for AstraZeneca.

Nearly identical results were observed in the smaller group of people with ultralow HER2 levels, equating to a similar five-month difference versus chemo in so-called progression-free survival. Though the study wasn’t powered to detect a statistical difference on that measure, experts interviewed by BioPharma Dive still say the finding is convincing.

“This data, in addition to data from other studies, do suggest that this population is likely to benefit,” added Rachel Layman, a breast medical oncologist at The University of Texas MD Anderson Cancer Center. Layman also didn’t take part in the trial, but is an investigator in a different Enhertu study.

There are some caveats. The study hasn’t continued for long enough to clearly tell whether Enhertu extends survival. Enhertu was also associated with higher rates of serious drug-related side effects, among them a type of lung scarring — interstitial lung disease — that can require rigorous monitoring to detect and manage. While this side effect wasn’t serious for most patients who received Enhertu, about 5% stopped treatment because of it and three died.

Interstitial lung disease is the “biggest downside” of Enhertu and “gives me pause” before prescribing, Layman said.

Waks, of Dana-Farber, added that doctors should carefully choose who to treat with Enhertu. An oft-prescribed chemotherapy called capecitabine is administered orally, unlike the intravenously infused Enhertu, and that drug isn’t associated with lung scarring or hair loss, the latter of which is also a concern for patients, she said.

While the efficacy reported is “quite impressive,” Waks said, “it is problematic to just say, based on these results, we're going to move this agent into the first line for every eligible patient.”

According to estimates from AstraZeneca, as many as two-thirds of hormone receptor-positive breast cancers typically classified as negative for HER2 expression actually have low levels of the protein. The company says another 20% to 25% may have “ultralow” HER2 expression.

Hormone therapies and CDK4/6 drugs are widely used to treat those patients first. If their cancers progress, people typically move on to chemotherapy, with limited benefits. Enhertu is currently only available after chemo.

AstraZeneca and Daiichi have been trying to show the drug can be given earlier, part of a plan to make antibody-drug conjugates, or ADCs, a mainstay in cancer care. ADCs are designed to deliver toxins more precisely to tumors than traditional chemo, a sort of “next-generation chemotherapy,” Layman says. After decades of research, they’ve recently come of age, catalyzing billions of dollars in deals and investments by pharmaceutical and biotechnology companies.

AstraZeneca and Daiichi, through two ADC-focused collaborations, have made these drugs a priority. In a recent presentation, for example, AstraZeneca executives discussed the potential for ADCs to supplant chemotherapy in many tumor types, starting with Enhertu in breast cancer and eventually moving to others.

“The key goal from this trial is to show the power of ADCs in truly replacing chemotherapy,” said Mohit Manrao, the senior vice president of AstraZeneca’s U.S. oncology division, in an interview. “We are seeing with this therapy, we can displace traditional chemotherapy and bring it earlier to the patients.”

AstraZeneca has already said it intends to share the trial’s results with regulators. Even if a new approval is forthcoming, though, some experts anticipate challenges in identifying people with ultralow HER2 expression. Already, clinicians are dealing with a learning curve following the 2022 clearance of Enhertu in HER2-low breast cancer. That approval forced doctors to think of HER2 expression beyond binary positive or negative terms, and made it important for pathologists to correctly identify low status in tumor samples.

According to Layman, the lab technique used to make those judgments is somewhat subjective, meaning each pathologist might report a different result from the same sample. Adding an ultralow category adds another wrinkle that may be harder for some pathologists — particularly those in community oncology centers — to iron out, she said.

“This is a new category,” Layman said. “I think there are concerns about the applicability to the country as a whole.”

Pharmaceutical companies employ many different strategies when building their cancer drug pipelines, but one recent commonality among them is a belief in the future of targeted therapies known as antibody-drug conjugates.

Many of the leading cancer drugmakers have at least one or two antibody-drug conjugates, or ADCs, in development. Others, such as Pfizer, Johnson & Johnson and Merck & Co., have used buyouts or partnerships to build an ADC portfolio.

One of the best-selling ADCs on the market is AstraZeneca and Daiichi Sankyo’s Enhertu, which brought in combined sales of $2.5 billion in 2023, almost double the year before. The two companies formed a $7 billion alliance around Enhertu in 2019 and since then, the drug has secured multiple approvals and changed the way some breast cancers are treated.

Over that time, AstraZeneca has made ADCs a more substantial part of its overall pipeline alongside radiopharmaceuticals and immunotherapies, giving the company many potential combinations to work with, said Carlos Doti, vice president and head of medical affairs for its U.S. oncology division.

“We started our ADC journey with the Daiichi partnership, and now we’re bringing seven or eight different molecules from our own platform,” Doti said.

Since the approval of the first ADC, Mylotarg, in 2000, researchers have improved the drugs’ capabilities by trying different components and changing the way they are linked together. As a result, newer ADCs could be used for more tumor types, and alongside other therapies, such as drugs that spur the immune system to fight cancer.

“ADCs can sort of be like a choose-your-own-adventure — you have all these different [tools] available to you, and now you can identify where there’s unmet need,” Doti said. “What was clear from [the American Society of Clinical Oncology’s annual meeting this year], the combination of ADCs and [immunotherapies] will change the first line of treatment by combining that immune system enhancement and directed therapy together.”

AstraZeneca, for instance, presented results suggesting Enhertu should be used ahead of chemotherapy in a common type of advanced breast cancer, and in a broader group of patients. That finding is a step forward in a broader strategy by the company to use ADCs to supplant chemo in many tumor types.

But AstraZeneca is advancing other ADCs as well. The company has prospects in early clinical studies for lymphoma, leukemia, multiple myeloma and other malignancies. It is also aligned with Daiichi on datopotamab deruxtecan, which could be approved later this year for a form of lung cancer.

ADCs, which chemically link a targeting antibody to a tumor-killing toxin, were originally seen as a way to more precisely deliver chemotherapies. But AstraZeneca and its peers are moving beyond chemo to transport other payloads, Doti said.

“We’re improving our technology, and getting better antibodies to direct where it needs to go, and using linkers that only release the payload at the point of delivery,” Doti said. “So if you see a lot of things going on for us and others, it’s that we're not just working on delivering chemotherapy in the payload anymore.”

AbbVie’s oncology pivot

AbbVie’s cancer drug portfolio is headlined by treatments for blood malignancies. Recently, though, the big drugmaker has made solid tumors a focus, and ADCs are a key part of its plan. Last year, the company spent $10 billion on ADC developer ImmunoGen, giving it an ovarian cancer drug, Elahere, as well as a group of experimental medicines that complemented its internal ADC research.

“We’ve been working in the hematological space, but solid tumors have a larger unmet need in oncology, and so it was a natural next step,” said Pedro Valencia, vice president of AbbVie’s solid tumor pipeline and strategy. “One of the overarching strategies is a focus around ADCs, thinking about what we call the ADC toolkit with a series of novel antibodies, novel targets, novel payloads that can be first and also best in class.”

AbbVie is targeting tumors, like colorectal and small-cell lung cancers, that many other medicines haven’t treated well in the past. Some of its prospects also deliver a so-called TOP1 inhibitor to tumors, as Enhertu does.

“The reasoning is we have the ability to replace chemotherapy that has been used for decades, and … we’re trying to do that in colorectal, ovarian, non-small cell lung and small cell lung cancers,” Valencia said.

Although AbbVie is behind many other pharmaceutical companies in treating these types of tumors, Valencia said that gives it a chance to build franchises from scratch, as it did with Humira in immunology and Venclexta in blood cancers. “We like to be the newcomers,” Valencia said.

Like AstraZeneca, AbbVie envisions combinations of ADCs and other drug types as expanding the number of people who can benefit from treatment.

“If you combine ADCs and immunotherapies, for example, I see that as the next big wave to unlock patients who haven’t been unlocked before,” Valencia said.

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References

1. Garcia-Murillas I, Schiavon G, Weigelt B, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7(302):302ra133. doi:10.1126/scitranslmed.aab0021

AstraZeneca’s plan to reach $80 billion in sales by 2030 relies heavily on a slate of roughly one dozen cancer drugs it expects will become blockbuster sellers at their peak, according to a presentation to investors that executives outlined in late May.

One of the drugs, the lung cancer treatment Tagrisso, has already exceeded $5 billion in annual sales and another, Imfinzi, is approaching that mark. But four use technologies AstraZeneca hasn’t previously employed and will either take on or trail products from rival drugmakers.

Broadly, AstraZeneca aims to develop drugs that supplant toxic chemotherapies as well as immunotherapies known as checkpoint inhibitors. Its large pipeline of antibody-drug conjugates, which add tumor cell-targeting to chemical toxins, will play a large role in achieving the former goal.

AstraZeneca has reinvented itself over the past decade, shifting from its prior focus on mental health, respiratory and cholesterol drugs to emphasize oncology. There, its strength has been in targeted therapies and in antibody-drug conjugates, as it has come late to fields like immunotherapy and radiopharmaceuticals. Imfinzi, the company’s flagship immunotherapy, arrived fifth to market in the U.S. and last year earned sales that were one-fifth of Merck & Co.’s Keytruda, the leader in the space.

AstraZeneca plans to change that picture. In immunotherapy, it’s developing bispecific antibodies that target the PD-1 pathway. One, called rilvegostomig, binds to another immunity-modulating pathway called TIGIT, which has proven a difficult target even in combination with PD-1 drugs.

Another, known as volrustomig, binds to PD-1 and a target called CTLA-4, essentially duplicating a two-drug combination of Imfinzi with another immunotherapy called Imjudo.

AstraZeneca also plans to make a mark in cell therapy, which has so far been led by Novartis, Gilead and Bristol Myers Squibb, as well as biotechnology companies like Legend Biotech and Bluebird bio. Leading AstraZeneca’s efforts is a dual-acting therapy that hits a protein active on multiple myeloma cells, along with CD19. The company claims it can make that drug, which would compete with Legend and J&J’s Carvykti and Bristol Myers’ Abecma, in a few days, rather than the weeks current CAR-T therapies take to produce.

Outside of immunotherapy, AstraZeneca is advancing a new type of hormone therapy for breast cancer that it’s testing in post-surgical and inoperable settings, paired with types of targeted therapies in some cases. In breast cancer, it is also studying a so-called PARP inhibitor known as saruparib, which could potentially replace its $2 billion-a-year drug Lynparza.

Antibody-drug conjugates, which pair the tumor-targeting of antibodies with the cell-killing power of chemotherapies, will continue to play a large role in AstraZeneca’s cancer drug plans, too.

The company already markets one, the breast cancer drug Enhertu, and has another now before regulators, called datopotamab deruxtecan and also for breast cancer. Peter Welford, an analyst at Jefferies, forecasts that latter drug will earn nearly $6 billion in sales in 2030.

AstraZeneca has six other clinical-stage ADCs. Combined, its ADC assets could be used in 17 different types of cancer.

Beyond 2030, the drugmaker expects to add radiopharmaceuticals, or hybrid radiation-emitting drugs, to its arsenal. AstraZeneca paid $2.4 billion in March to acquire Fusion Pharmaceuticals, a developer of such products that has a prostate cancer drug in Phase 2.

Mariana Oncology arrived at the J.P. Morgan Healthcare Conference this past January with momentum. The radiopharmaceutical drug developer had secured $175 million in fresh funding four months prior and, in the time since, seen two competitors in its field acquired via multibillion-dollar acquisitions.

The result was a full calendar of meetings for Mariana’s executive team. “The inbound interest was broad and almost frenetic,” said company CEO Simon Read in an interview. “The business development deals in the run-up to J.P. Morgan had really conditioned the marketplace.”

One of those conversations led to Mariana’s own deal, a $1 billion buyout by Novartis that the companies announced in early May. 

According to Read, Mariana saw the chance to combine with Novartis, a radiopharmaceutical leader that sells two of the targeted radiation drugs, as a “perfect marriage.”

“If you want to maximize the value of [your pipeline], it helps to be able to add scale. You can carry on raising more and more money, but having a party that can add scale, knows how to commercialize these drugs, that's probably a better strategy,” Read said.

Novartis has a good claim at being expert. The company invested heavily in radiopharmaceuticals, acquiring its approved drugs Pluvicto and Lutathera through a pair of acquisitions several years ago and building out the manufacturing to support them since.

Novartis’ success with Pluvicto in prostate cancer has motivated others, Mariana among them, to follow into the field. “We began thinking in mid-2020 about the makeup of the company. We had been struck by the compelling efficacy that was coming out the clinic with Pluvicto,” Read said.

Eli Lilly’s $1.4 billion purchase of Point BioPharma last October, meanwhile, gave Lilly a potential competitor to Pluvicto, as well as an entry point into radiopharmaceuticals.

Radiopharmaceuticals combine an isotope, like lutetium or actinium, with a targeting molecule meant to shepherd the cell-killing radiation directly to the tumor. Essentially, the drugs offer a more precise way to target cancers with less risk of harming healthy tissue, as beamed or implanted radiation can.

But they’re tricky to manufacture and, because radioactive isotopes degrade over time, require a precisely choreographed supply chain to get doses to patients in just the right window.

Even Novartis has run into challenges, temporarily pausing production in 2022 to resolve certain quality issues and then struggling to keep up with demand for Pluvicto.

The company has added new factories and scaled up capacity in response. A new plant in Indianapolis came on line earlier this year, for example, increasing the number of doses Novartis can make annually to 250,000.

“It was a significant investment for the organization,” said Jeevan Virk, therapeutic area strategy head for radiopharmaceuticals at Novartis, in a February interview. “We now feel we’re in a space where we’re able to deliver on the promise of unconstrained supply.”

Spanning some 70,000 square feet, the facility currently has two manufacturing lines operating, but has space to quadruple that if needed, according to Sergio Cerdas, Novartis’ global head of radioligand therapies.

Novartis has additional radiopharmaceutical facilities in New Jersey, Italy and Spain, and is planning to open sites in Japan and China.

Mariana has its own manufacturing already set up, which it will use to supply its lead radiopharmaceutical candidate for small cell lung cancer when that enters clinical testing later this year.

That distinguishes its deal with Novartis from other recent acquisitions of RayzeBio by Bristol Myers Squibb and of Fusion Pharmaceuticals by AstraZeneca, Read said.

“The narrative of those deals were about, ‘let’s secure supply chain, let’s secure manufacturing as table stakes to get into this space,” added Read. “[Mariana’s deal] was slightly different in so much as this was about a fantastic pipeline and portfolio complementarity.”

Mariana hasn’t yet disclosed the target of its small cell lung cancer treatment, but the candidate uses actinium, which a number of other companies, Novartis included, are exploring as an alternative radioisotope to lutetium.

The biotechnology company’s pipeline also contains other preclinical-stage programs in solid tumors like breast and prostate cancer.

Importantly, Read said, Mariana can match the isotope to the tumor it’s targeting. “We have the flexibility to put any payload we want on our molecules.”

When the Food and Drug Administration approved a new prostate cancer drug in 2022, it validated a bet made by Novartis to acquire the drug’s maker, Endocyte. The decision was also another step forward for a long-studied research field that is finally coming of age.

The medicine, Pluvicto, is known as a “radiopharmaceutical.” Unlike the small molecule or biologic medicines drugmakers use to flip cellular switches on or off, radiopharmaceuticals are designed to precisely deliver radioactive material into the body. The result is a targeted punch of radiation that can knock out tumors in a way other drugs can’t.

However, since Pluvicto’s approval, Novartis has hit challenges meeting demand, highlighting one of the many issues that has slowed development of radiopharmaceuticals. They’re difficult to produce, distribute and administer. The earliest examples never lived up to commercial expectations, hamstrung by manufacturing problems, competition, high costs and safety concerns. GSK stopped making one, known as Bexxar, in 2014. Another, named Zevalin and originally developed by Idec Pharmaceuticals, never became a big seller.

A group of companies, from biotechnology startups to pharmaceutical giants, think they’ve solved these problems. Borrowing from progress in another cancer drug field, they’re leaning on technical advancements that have enabled researchers to design medicines capable of safely delivering a radioisotope to just the right spot.

Novartis is the most invested, having spent $6 billion on acquisitions of Endocyte, Advanced Accelerator Applications and Mariana Oncology. Right alongside Novartis is Bayer, which has also brought a radiopharmaceutical to market and is testing others. Eli Lilly, Bristol Myers Squibb and AstraZeneca have all bought into the field.

Behind them are a handful of publicly traded companies and at least a dozen biotech startups, making radiopharmaceuticals a hotly competitive area of drug research. Here’s where things stand:

What are radiopharmaceuticals, and how do they work?

Born shortly after the discovery of the X-ray, radiation therapy has more than a century of history in cancer treatment. It’s a way of using high-energy particles or waves to damage the DNA of cancer cells, preventing division and growth.

Along with surgery, radiation therapy is a mainstay of cancer care, used to treat or prevent the recurrence of tumors in more than half of people with the disease, according to the American Cancer Society.

But radiation therapy is a blunt force. Rays beamed from outside the body can damage healthy tissue, while a more targeted, inside-the-body approach is costly and complex.

By comparison, radiopharmaceuticals can deliver the destructive power of radiation directly into tumors. They are akin to microscopic smart bombs — radioactive material guided by a molecular courier to cells with specific protein flags.

With Novartis’ drug Pluvicto, a radioisotope known as lutetium is chemically fused to a small molecule that binds to PSMA, a protein overexpressed in most prostate cancers. Novartis’ other radiopharmaceutical, Lutathera, delivers radioactive lutetium to SSTR, a target found on certain neuroendocrine tumors.

The drugs are complex, made of hand-picked parts. Different radioactive materials may weigh more or less, last longer or pack a bigger punch. Some radiopharmaceuticals may require a “chelator,” a molecule that keeps the radioactive material intact as it’s carried through the body.

Drugmakers also have to design chemical “linkers” that hold their therapies together, but don’t stick around too long after reaching their target. A molecular guide that seeks out malignant cells is another necessary component.

Once designed, radiopharmaceuticals are tricky to produce at scale. Supplies of radioactive materials are limited, and their transport is controlled. The drugs must be made and delivered quickly, before the radioactive components decay too much.

Why are radiopharmaceuticals a hot area of investment?

Interest in radiopharmaceuticals mirrors the ascent of another class of targeted cancer medicines, known as antibody-drug conjugates, or ADCs.

Like radiopharmaceuticals, ADCs deliver a toxic substance, usually a chemical, directly to a tumor. After years of slow progress, they’ve undergone a renaissance catalyzed by technical advances, regulatory approvals and interest from large drugmakers. Venture investors are in turn backing new startups.

Radiopharmaceuticals are now in the spotlight, too. Despite the poor sales of the field’s first medicines, newer drugs are performing better. Studies supporting some, like Pluvicto, have shown radiopharmaceutical drugs can extend survival and, in some cases, outperform other types of treatments.

Radiopharmaceutical drugs are “now being recognized as an effective, safe, and economically and logistically viable treatment modality,” wrote physicians from Johns Hopkins University School of Medicine and Memorial Sloan Kettering Cancer Center, in a 2020 article in Nature Reviews Drug Discovery.

As is often the case, large pharma investment is sparking a chain reaction of activity. Novartis’ acquisitions of Advanced Accelerator and Endocyte yielded Lutathera and Pluvicto, which, despite production challenges, are seeing strong demand. Bayer reached close to $500 million in peak yearly sales with its radiopharmaceutical Xofigo; it’s now working on newer medicines and, in 2021, acquired two startups.

Diagnostics company Lantheus Holdings bought the maker of Azedra, another radiopharmaceutical recently approved by the FDA for rare neuroendocrine tumors.

Those deals, along with radiochemistry advances and a “greater ability to innovate in ‘complex’ therapeutic modalities,” have spurred a wave of investments in new radiopharmaceutical companies, wrote Faisal Khurshid, an analyst with Leerink Partners, in a 2023 report.

Some, like Fusion Pharmaceuticals and RayzeBio, are going after the same targets as Pluvicto and Lutathera, but with different radioactive components or guiding molecules. Both were recently acquired, by AstraZeneca and Bristol Myers, respectively. 

Others are pursuing different cancer-associated proteins. The startup Abdera Therapeutics has a program in development aimed at DLL3, a long-studied target in a tough-to-treat form of lung cancer. Belgian biotech Precirix is evaluating a radiopharmaceutical for tumors driven to growth by HER2, a well-known cancer gene.

Which companies are working on it, and who is backing them?

More than a dozen radiopharmaceutical startups have launched in recent years. Many have pulled in sizable funding rounds, sometimes with overlapping investor groups.

In April, Abdera debuted with $142 million in funding and backers led by venBio and Versant Ventures. Those two investors also launched RayzeBio, which raised $418 million before its buyout.

Convergent Therapeutics launched in May with $90 million from RA Capital Management and OrbiMed. RA Capital also helped incubate Mariana Oncology alongside Atlas Venture and Access Biotechnology.

Aktis Oncology has secured $161 million in funding from Novartis, Merck & Co. and Bristol Myers Squibb, among others, since arriving in 2021.

Precirix is backed by Forbion and Jeito Capital and has raised 117 million euros since 2018. Germany-based Isotope Technologies Munich, or ITM, in June secured 255 million euros in a large funding round for a European biotech.

Artbio debuted in June with seed funding from Omega Funds and F-Prime Capital. It’s run by Emanuele Ostuni, the former head of Novartis Oncology’s cell and gene therapy operations in Europe, and was founded by the inventors of Xofigo.

Other firms in the mix include France’s Atonco Pharma, Australia’s GlyTherix, China-based Ablaze Pharmaceuticals, University of Connecticut spinout Nami Therapeutics and Boston-based Ratio Therapeutics.

These young companies join a handful of publicly traded biotechs as well as initiatives started by diagnostics firms or suppliers of nuclear material.

Pfizer believes the answer to its sliding valuation lies in oncology. 

The company, which is coming off one of the worst years in its history, unveiled Feb. 29 a new business unit dedicated to cancer research. The division, created in the wake of Pfizer’s $43 billion buyout of Seagen last year, houses a sprawling portfolio of experimental medicines both companies discovered and acquired through deals. It also includes the marketed drugs Pfizer and Seagen have long been selling for a variety of tumor types. 

Pfizer claims the pipeline it now has could produce more than eight blockbuster medicines by 2030, up from five today, and double the number of patients the company’s drugs currently treat. By then, biologic medicines should account for nearly two-thirds of its oncology revenue, up substantially from the 6% they comprise now, Pfizer said. 

To achieve those goals, Pfizer will need steady sales growth and additional approvals for its currently marketed medicines. It will also need a pipeline of 16 experimental drugs across four broad areas of cancer research to come through in testing. 

The oncology push comes after a tumultuous year for Pfizer marked by fast-declining sales for its COVID-19 treatments and little growth elsewhere. Company shares lost a large chunk of their value, and Pfizer responded with a cost-cutting plan that aims to reduce expenditures by $4 billion. Pfizer is facing pressure elsewhere too, as looming patent expirations and competition to some of its top-selling medicines leave the company with “uncertain long-term .. prospects,” wrote Leerink Partners analyst David Risinger. 

Pfizer’s breast cancer medicine Ibrance, for example, has seen its market share decline amid a growing threat from Eli Lilly’s Verzenio and Novartis’ Kisqali. Oncology revenue has been stagnant too as sales in 2023 fell from $12.1 billion to $11.6 billion.

The company anticipates a boost from Seagen’s portfolio, which includes the marketed medicines Adcetris and Padcev and could boost its oncology revenues by another $10 billion by the end of the decade. Pfizer believes its marketing and manufacturing might can accelerate sales of both, surpassing what Seagen was able to do on its own. 

Study results due later this year and early next could show whether Pfizer is on that path. The company expects readouts from marketed and experimental drugs in its four main areas of oncology research – thoracic, breast, genitourinary and blood cancers. Pfizer is also launching Padcev in first-line bladder cancers, a setting analysts believe could transform the drug into a multi-billion dollar product. 

Additionally, the company is running Phase 3 trials for newer prostate and breast cancer drug prospects, including an experimental medicine called atirmociclib that could potentially supplant Ibrance if successful in a head-to-head trial. 

After attending Pfizer’s presentation, Louise Chen, an analyst for Cantor Fitzgerald, wrote that she believes the oncology business will be the company’s “largest growth driver through 2030,” something that “is not reflected in the stock's valuation yet.”

She added that Pfizer is “being conservative” in its revenue estimates because of Padcev’s likely growth in bladder cancer as well as “increasing usage” of antibody-drug conjugates, Seagen’s specialty.  

Merck & Co.’s sweeping cancer drug alliance with Daiichi Sankyo in October 2023 highlighted the pharmaceutical industry’s newfound enthusiasm for so-called antibody-drug conjugates, a class of medicines that’s yielded major products like Seagen’s Adcetris, Roche’s Kadcyla and AstraZeneca’s Enhertu. 

Earlier in 2023, Pfizer agreed to pay $43 billion to acquire Seagen, the field’s pioneer. A few years prior, Gilead paid $21 billion to buy Immunomedics and its antibody-drug conjugate Trodelvy. 

Merck, which reportedly had also sought to buy Seagen, agreed to send Daiichi Sankyo $5.5 billion over the next two years. But the deal’s total value is as high as $22 billion, if all sales milestones are met, making it one of the most lucrative pharma licensing arrangements in recent history. 

It will add to some $16 billion worth of antibody-drug conjugate licensing deals signed in 2022, according to analytics company Global Data.

Antibody-drug conjugates, or ADCs, pair the tumor-cell killing capabilities of chemotherapy with the targeting technology of synthetic antibodies. When the combined drug binds with a cancer cell, a chemical linker unleashes the toxin into the cell, sparing surrounding healthy tissue from exposure.

Merck has already been active in the field, paying Seagen $1.7 billion in cash, licensing fees and equity in 2020 for rights to an experimental ADC as well as to the marketed drug Tukysa. A few months later it signed a $3 billion deal to acquire VelosBio. And last year, it paid Kelun-Biotech $175 million upfront for rights to a number of early-stage ADCs.

In partnering with Daiichi Sankyo, Merck may have been spurred on by one of the more audacious big pharma bets on ADCs. In 2019, AstraZeneca paid Daiichi Sankyo more than $1 billion upfront and promised an additional $5.6 billion in contingent payments for rights to the drug that became Enhertu, a deal it funded with a $3.5 billion share offering. That bet is on the verge of returning blockbuster annual revenue for AstraZeneca, which reported $104 million in product sales and $475 million in alliance revenue through the first six months of 2023.

Gilead’s deal for Immunomedics was also bold as it sought to build an oncology business, although it had the cash from its HIV and hepatitis C drugs to tap. Like Enhertu, Trodelvy could also record blockbuster numbers soon, having accounted for $482 million in sales through June 30.

Other companies have been joining in. Bristol Myers Squibb, Merck’s rival in immunotherapy, paid Eisai $650 million in 2021 for rights to an ADC the Japanese drugmaker was developing for tumors positive for folate receptor-alpha, which include endometrial, ovarian, lung and breast cancers.

BioNTech, which made a name as a developer of mRNA vaccines and drugs, earlier this year signed a $170 million up front deal with Duality for rights to two ADCs.

Eli Lilly has also become active in the last two years, buying a German biotech called Emergence for its ADC pipeline, signing a deal with ImmunoGen, and acquiring French ADC developer called Mablink Bioscience.

AbbVie is expanding its investment in targeted cancer medicines, announcing Nov. 30 a $10.1 billion deal to acquire ImmunoGen, a pioneer in the field of so-called antibody-drug conjugates, and its newly approved ovarian cancer treatment Elahere.

The transaction was 2023’s fourth-largest biotechnology buyout and came as AbbVie’s oncology business is sputtering. Revenues for the company’s flagship drug Imbruvica have shrunk by more than one-fifth year over year through the first nine months of 2023, as competing therapies with fewer side effects have taken market share.

Elahere gives AbbVie an on-market drug that could help boost sales as the company awaits clinical trial results and the potential approval of experimental cancer drugs in its pipeline.

Robert Michael, AbbVie’s chief operating officer, highlighted Elahere’s rapid market adoption on a Nov. 30 call with investors. Sales, he noted, are already annualizing above $400 million, which he said would put it “on track to be one of the most successful new product launches in oncology.”

Elahere would also be the only drug in AbbVie’s portfolio approved to treat a solid tumor, rather than the blood cancers that Imbruvica and AbbVie’s other marketed medicines target.

“It has been a strategic priority for AbbVie to establish a strong foundation in solid tumors,” said AbbVie CEO Rick Gonzalez on the call.

ImmunoGen’s focus on so-called “antibody-drug conjugates,” which combine targeting antibodies with cancer-killing chemotherapy, matches AbbVie’s own research strategy. The company has emphasized development of the medicines, known as ADCs for short, and lists five in its pipeline.

Founded in 1981, ImmunoGen was an early innovator in the ADC field, developing the targeting biological molecules, the tumor killing chemical payload and the molecules that link them.

Its technology helped make possible the Roche drug Kadcyla and the Sanofi drug Sarclisa. Still, its own drug development efforts didn’t bear fruit until the Food and Drug Administration last year gave conditional approval to Elahere.

The drug is now used for people with ovarian cancer whose disease has progressed despite one to three rounds of chemotherapy and whose tumors have high levels of a protein called folate receptor alpha. AbbVie estimates a majority of ovarian cancer patients have this biomarker.

A confirmatory trial of the drug recently succeeded, showing treatment reduced the risk of progression or death compared with chemotherapy in patients whose disease has worsened following at least one round of chemotherapy.

ImmunoGen is also approaching an important data readout for a second experimental drug called pivekimab sunirine in a rare bone marrow and blood cancer. That medicine is also in earlier testing for leukemia.

The biotech’s antibody-drug conjugates will join in late-stage testing of AbbVie’s most advanced ADC, telisotuzumab vedotin, which is in lung cancer trials.

The $10.1 billion deal continues pharma’s lavish spending on ADC developers. Pfizer earlier this year agreed to pay $43 billion to acquire Seagen, another pioneer in the field, while Merck & Co. signed a big collaboration deal with Daiichi Sankyo worth $5.5 billion over the first two years.

In 2020, Gilead spent $21 billion to buy Immunomedics, which had developed and launched an ADC called Trodelvy in breast cancer.