Oncology

Big Pharma will need to pony up for some of its biggest price hikes. The industry expects invoices from the government later this year as a penalty for raising drug prices faster than the rate of inflation. 

Drug companies are required to pay inflation penalties to Medicare when prescription drug prices increase faster than the rate of inflation for certain drugs. The requirement is part of the Inflation Reduction Act, and the latest round of penalties announced in June includes 64 drugs, several of which come from Big Pharma.

The list of treatments doesn’t overlap with the first 10 drugs that are up for price negotiations with Medicare, which is a separate provision of the IRA. Those price adjustments are currently in negotiations and will become effective in 2026.

The inflation-related rebates are based on average sales price, and drug companies are required to pay Medicare the difference if the price rises faster than the inflation rate, equal to the amount of units sold to Medicare. The rebates are deposited into the Medicare Trust Fund, and people with the government-run insurance plan will see temporary savings on their coinsurance rates to make up the price difference. From July 1 through Sept. 30, people with Medicare will see savings as high as $4,593 per day depending on the drug, the CMS said. 

The rebate program began last year, when Medicare required payment for 46 drugs. The latest round includes several blockbuster drugs from Big Pharma. While pharma companies are also grappling with price negotiations, here are three cancer treatments on the rebate list that pharma giants will need to account for. 

Adcetris — Pfizer

Adcetris was Seagen’s top-selling drug when Pfizer acquired the pharma company for $43 billion late last year. Revenue reached $279 million during the second quarter of 2024, according to Pfizer’s earnings report this week, up from $257 million in the first quarter.

As a result of landing on the CMS’ inflation penalty list, the inflation-adjusted coinsurance percentage of Adcetris, an antibody-drug conjugate for Hodgkin lymphoma, will drop from 20% to 18.6%, giving recipients temporarily lower costs for themselves, the agency said.

Despite the penalties directed at Adcetris, Pfizer CEO Albert Bourla noted the IRA isn’t all bad news for the company thanks to a potential volume increase on vaccines related to cost-sharing with Medicare recipients. 

Abecma, Breyanzi —Bristol Myers Squibb

The CAR-T cell therapy Abecma hasn’t yet reached blockbuster status for Bristol Myers Squibb and partner 2seventy bio since it was approved in 2021 for multiple myeloma. The therapy reached $388 million in revenue in 2022, but revenue has since taken a dip with rising CAR-T competition, falling to $358 million in 2023. 

Still, Abecma could be due for growth, as 2seventy bio announced a new strategic path focused on commercialization at the start of the year that includes expanding the label.

Also on the penalty list is BMS’ Breyanzi, a CD19-directed CAR-T cell therapy approved for B-cell lymphoma. Revenue totaled $303 million in 2023, up from $182 million in 2022. The company snagged U.S. approval in follicular lymphoma and mantle cell lymphoma this year, and sales are expected to increase in the coming years. In the first six months of the year, Breyanzi revenue is up 52%. 

The inflation penalties are not the only government initiative set to impact BMS drug prices. The company is separately facing pressure from the IRA price negotiations with the blockbuster blood thinner Eliquis in the first wave of 10 drugs. Developed with Pfizer, Eliquis reached $12.2 billion in 2023 revenue, according to BMS’ end-of-year earnings. However, the company is still bullish on the drug’s short- and medium-term value now that price negotiations are likely set in stone, executives said.

Padcev —Pfizer, Astellas Pharma

The CMS called out the bladder cancer drug Padcev from Pfizer and Astellas Pharmaceuticals for an egregious price hike. The drug’s price has increased faster than the rate of inflation every quarter since the Part B rebate program went into effect. As a result, the CMS has adjusted the coinsurance rate since 2023 so Medicare recipients are paying lower amounts to account for the price hikes. 

“A beneficiary taking Padcev as part of their cancer treatment may have saved as much as $1,181 from April 1, 2023, through March 31, 2024, depending on their coverage and course of treatment,” the CMS said in a press release.

Along with Adcetris, Padcev was another drug Pfizer acquired in the Seagen deal to bolster its oncology portfolio. During the second quarter of 2024, revenue for Padcev reached $394 million, according to the company’s earnings report released this week. Revenue was better than forecast by analysts and contributed to Pfizer raising its full-year revenue guidance from $59.5 billion to $62.5 billion, Reuters reported. 

As a consumer company, 23andMe is well known in the public sphere for mail-in genetic test kits that provide a detailed family history. But alongside that business, the biotech is also developing drugs using its massive database of genomic information, getting closer to a cancer treatment of its own.

23andMe is building on the success of immunotherapies like Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo, which are checkpoint inhibitors that block a pathway between tumors and the immune system, allowing the body to fight back against cancer. And with a wealth of knowledge at their fingertips, researchers at 23andMe have uncovered new pathways that could have a similar effect and add to the arsenal of oncology drugs, said Dr. Jennifer Low, head of the company’s therapeutics department.

By identifying genetic variants from the world’s largest database, 23andMe found target biomarkers in the CD200 pathway that, when blocked with the treatment 23ME-00610, has shown preliminary clinical benefit in a mid-stage study of patients with neuroendocrine and ovarian cancer. As the first antibody to target this pathway, Low and her team hope this marks a foray into precision medicine that has been discussed in the industry for years.

And 23andMe needs a win. The company has been mired in controversy, from the ethics of using genetic information for research to a high-profile data breach. Last year, the therapeutics division had to cut jobs as biotech investment wanes and the company’s shares circle the drain.

But Low is optimistic about the company’s foothold in the drugmaking arena. Here, we spoke to the therapeutics head about the role genetic databases can play in discovering and developing new treatments for disease like cancer, how understanding demographics would help improve clinical trial diversity and the potential for collaboration with traditional pharma companies in the future.

This interview has been edited for brevity and style.

PHARMAVOICE: How has 23andMe’s huge customer database helped guide the company to the development of oncology checkpoint inhibitors?

DR. JENNIFER LOW: One of the biggest challenges across pharma is that we use animal models to try to understand human biology, but we’re very limited in terms of what will actually translate. Animal models don’t recapitulate what’s going on in people. And so the big advantage to the 23andMe database is that this is human data, human genetics — we have over 15 million genotyped individuals from our customer database, and this allows us to make statistical connections between genetics and what people experience in their biology. We ask about family history and disease, but we also ask them about a lot of other things, like, what is their susceptibility to toenail fungus? Or are they the kind of person who’s always getting attacked by mosquitoes? And this allows us to have subtlety around biology that you’re not going to get in a medical record.

That gives us a large amount of information so that we can also see subtle differences in immune function and how that connects with a propensity for developing cancer. Using that combination of information, we can draw insights into which parts of immune biology may be important for a person’s immune system to be able to see and attack cancer. And we can make tweaks to the drugs that we’re making to realign the immune system to no longer be blind to that cancer.

When you look at the success of immunotherapies like Keytruda, they are still limited by a patient’s genetics. How can 23andMe improve upon that to create what could be the next wave of checkpoint inhibitors?

Checkpoint inhibitors have been a massive advance. In the beginning, immune therapies like interferon or IL-2 were really hard for patients to take and would only offer a smaller chance of long-term survival. Then the PD-1 and PD-L1 immunotherapies brought [survival] up past 20%, which is phenomenal — but 70% to 80% of people still are not getting the long-term benefit. And it’s likely … that there are other checkpoints that are important. So our first program, the CD200R1 program, affects a different checkpoint independent of PD-1 and PD-L1. You need a lot of different options to get the right constellation of effects, and you need to understand more about the immune system you’re trying to activate. Because 23andMe has a much broader understanding of the variability of the immune system, we’re finding targets that allow us to look at many different ways to approach it. We’re really excited about the potential for these drugs.

23andMe has come into some ethical questions about addressing demographics in genetic research. How does the database help bring more diversity into clinical trials?

The FDA is very concerned about the lack of breadth that occurs in a lot of clinical trials, and they want to see that diversity because the American population is very diverse and they need to understand more broadly. With our experience in genetics and increased insights into the differences, the rest of the industry will realize how important it is to have that additional information as well. The U.S. is only 30% of the global market for most drugs, and so it’s really important to think about that.

With precision medicine becoming more advanced, biomarker expansion is critical. Where do you see 23andMe’s database fitting into that down the road?

We’ve been talking for ages about personalized medicine because, even when we have broad labels like lung or breast cancer, for any individual person, their tumor and immune systems greatly influence how their medications will work and what will eventually enable their body to gain control of a tumor. For oncology, we tend to focus on the tumor itself, but we already know that it’s much bigger than that. We’re trying to understand those subtle differences and understand biological processes. And so 23andMe is doing a lot of work to look at multigenic causes and multigenic risk around the propensity for developing disease. I see 23andMe as a critical contributor to how to think about these big problems, and any company that wants to understand some of these aspects would be great to partner with. That’s one mechanism by which our influence could be much, much broader.

What’s the biggest challenge for 23andMe moving forward in the therapeutics area?

This is a tough market right now for small biotechs, which is what we are. As a result, we’ve had to make tough decisions around prioritization and focus — we announced that we needed to scale back our activities and made a really tough decision to let go of a number of our employees within therapeutics. We would love to be able to do everything, but I do feel confident that the organization is leaner, meaner and ready to accomplish a lot in a very efficient way.

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By PurpleLab

In today’s data-rich healthcare environment, real-world data (RWD) offers a treasure trove of insights. For oncology clinical trials, where cancer remains a leading global health challenge, effectively utilizing RWD can significantly enhance trial planning and patient outcomes. However, achieving this involves overcoming substantial obstacles. This article explores how strategic use of RWD can address these challenges and improve the efficacy of oncology clinical trials.

The Role of RWD in Oncology Clinical Trials

Successful oncology clinical trials hinge on identifying the right patients, providers and facilities. This process is particularly complex due to the personalized nature of cancer treatment. To navigate these complexities, it’s crucial to understand several key dimensions of patient data:

• Genetics: Identifying genetic variants linked to cancer susceptibility helps tailor treatments.
• Tumor and Immune Response: Analyzing how tumors interact with immune responses can guide the development of targeted therapies.
• Diagnosis Timing and Stage: Insights into the timing and stage of cancer can provide context for treatment efficacy and patient outcomes.
• Comorbidities: Understanding concurrent medical conditions can influence treatment plans and outcomes.
• Age and Race: Demographic factors impact cancer risk and treatment responses.

Challenges in Identifying the Right Participants

Finding eligible patients for oncology trials involves navigating several hurdles:

1. Patient Specificity: Trials require patients meeting precise criteria, which often require detailed genetic, diagnostic and demographic information. Misidentifying patients can skew results and pose risks.
2. Diversity: Trials need to reflect the general population’s diversity to ensure findings are applicable to a broad audience and adhere to FDA mandates. The mandate includes specific requirements such as increase representation, address of health disparities, development of inclusive studies and transparency for regulatory submission.
3. Data Variability: Medical terminology and data sources can vary, complicating patient identification. Standardizing and harmonizing this data is crucial for accurate trial planning.

The Critical Role of Healthcare Analytics

Healthcare analytics platforms play a pivotal role in transforming RWD into actionable insights. These platforms help address key challenges:

• Data Integration: Platforms like HealthNexus™ from PurpleLab®, harmonize data from various sources, making it easier to identify eligible patients and providers.
• Predictive Analytics: Advanced analytics generate actionable reports, providing insights into patient populations and trial outcomes.
• User-Friendly Interfaces: Modern platforms simplify data access, reducing the need for deep technical expertise.

HealthNexus: A Game-Changer for Oncology Trials

HealthNexus, powered by PurpleLab, exemplifies how a sophisticated analytics platform can revolutionize oncology clinical trials. It addresses common data-related challenges with several key features:

• Data Harmonization: HealthNexus integrates and standardizes data from disparate sources, ensuring comprehensive and accurate patient profiles.
• Actionable Insights: The platform generates predictive and quantitative reports, offering valuable insights for trial planning and execution.
• Ease of Use: Unlike traditional methods, HealthNexus simplifies data analysis without requiring specialized coding skills.

Applying HealthNexus in Clinical Trials

1. Finding Clinically Relevant Patients: HealthNexus enables the rapid identification of patient populations based on specific criteria, such as demographics, geographic location and payer channels.
2. Targeting Experienced Providers: The platform helps locate providers with relevant oncology experience and patient populations, streamlining the recruitment process.
3. Profiling Healthcare Providers and Sites: HealthNexus provides detailed profiles of providers and facilities, including practice characteristics, SDOH and quality scores. This ensures that the selected sites align with trial requirements and patient needs.

Overcoming Data Challenges

Despite its advantages, leveraging RWD still presents challenges:

• Volume and Complexity: Managing large volumes of data and ensuring its accuracy can be overwhelming. HealthNexus addresses this by offering a streamlined approach to data integration and analysis.
• Cost and Resource Intensity: Cleaning and analyzing raw data is resource-intensive. HealthNexus reduces these costs by providing pre-harmonized data and actionable insights.
• Compliance: Ensuring data privacy and compliance with regulations like HIPAA is critical. HealthNexus adheres to strict privacy standards, protecting patient information throughout the process.

Conclusion

Harnessing RWD is essential for advancing oncology clinical trials and improving patient outcomes. By integrating and analyzing data effectively, platforms like HealthNexus empower researchers to navigate the complexities of trial planning with greater precision. As the field of oncology evolves, leveraging real-world evidence will be key to driving forward cancer research and ultimately improving global health outcomes.

Reach out to PurpleLab today to learn more about how they can help accelerate and enhance your clinical trials.

BioNTech found runaway success during the COVID-19 pandemic when its Pfizer-partnered mRNA vaccine propelled the biotech to new heights. But now, with demand for the vaccine substantially lower and revenues way down in the first half of 2024, the pandemic darling is hedging its bets that an oncology pipeline will pay off in the coming years.

BioNTech’s meteoric rise has been met with a continued fall in 2024 following declining revenues in 2023. For the first half of the year, total revenues reached $347 million, down 119% from $1.6 billion during the same period in 2023, according to the company’s most recent earnings report. 

When COVID-19 vaccine sales were at their peak in 2021 and 2022, BioNTech reported yearly revenues of nearly $21 billion and $19 billion, respectively. Total losses for the company in the first half of 2024 reached $885 million.

With vaccine revenues down, BioNTech is ramping up its pipeline to find another potential blockbuster, increasing R&D spending 55% to $1.2 billion during the first six months of 2024 compared to the first half of 2023. The biotech currently has more than 40 candidates in the pipeline, including four in phase 3 trials, betting big on mRNA and establishing an mRNA manufacturing facility in Rwanda. Earlier this year, BioNTech said it expects to have 10 cancer indication approvals by 2030, starting with launches from 2026 onward.

But the COVID-19 focus isn’t over yet. CEO Uğur Şahin noted BioNTech has initiated the launch of a “new variant-adapted vaccine” that is expected to be approved and distributed in the “coming weeks and months,” he said during the earnings call with investors. Ryan Richardson, chief strategy officer, doubled down and said the COVID-19 products are “still a driver of our overall margins.”

mRNA cancer pipeline

Of the drugs in BioNTech’s pipeline, BNT111, an mRNA cancer vaccine being studied in melanoma, is a strong candidate, according to Lee Brown, global sector lead for healthcare at research firm Third Bridge. The vaccine, which triggers an immune response in patients with advanced melanoma, received fast track and rrphan drug designation from the FDA. The company recently released positive topline results from a phase 2 study in July, meeting the primary endpoint and improving overall response rate in combination with Regeneron’s Libtayo, Brown said.

The vaccine is a proof of concept for BioNTech’s off-the-shelf mRNA platform, dubbed FixVac, which has the flexibility to target multiple non-mutated antigens in most patients with a given tumor type, according to chief medical officer Dr. Özlem Türeci. Its other mRNA vaccine platform, iNeST, produces vaccines on demand and personalized to each patient. 

“This preliminary result is a significant milestone for our company and underscores our belief in the transformative potential of this new class of medicines and of our mRNA vaccine technology, which is a key pillar of our oncology strategy,” Sahin said in the earnings call.

The cancer vaccine market has legs, too, with the potential to reach more than $30 billion by the end of 2033, according to a prediction from consulting firm Towards Healthcare. However, BioNTech is not the only drugmaker working on a skin cancer vaccine. Merck & Co. and mRNA biotech Moderna also recently released mid-stage study results for their cancer vaccine in combination with Keytruda, finding the vaccine significantly boosted survival rates.

Oncology strategy

Elsewhere in the pipeline is BNT323, an antibody-drug conjugate candidate targeting the HER2 protein in metastatic breast cancer. BioNTech began a late-stage trial in January to test for progression-free survival. BioNTech is working with DualityBio on the candidate, and Richardson noted the company is expecting data from the phase 3 trial next year, with the potential for a 2026 launch. The drug also received breakthrough designation.

Another candidate in BioNTech’s R&D machine is its novel immuno-oncology drug BNT327, an anti-VEGF-A antibody candidate co-developed with Biotheus. The company is currently evaluating it as a combination therapy for multiple cancers, with plans to initiate more trials in the next 12 months, including potentially in combination with chemotherapy. BNT327 combines two validated mechanisms of action that blocks tumor angiogenesis and reduces tumor cell proliferation and survival. 

“These novel BNT327 combinations may open up new areas of activity for our anti-VEGF-A and anti-PD-L1 molecule,” Tureci said during the earnings call.

But while BioNTech is planning to expand trials, Summit Technologies is further along with a similar drug candidate, ivonescimab, that also makes use of both the PD-1 and VEGF pathways. The company is already in phase 3 trials with the candidate, while BioNTech is launching its late-stage studies this year. 

BioNTech is pursuing BNT327 more broadly in its approach.

“Our approach here is to be broad with regard to the indications, which we will pursue also in potentially registrational trials,” Türeci said. “We are well poised for that. …We have a wealth of data already and can pick the indications and expand that as they mature.”

Despite promising candidates under development, not everything in the pipeline is still moving forward. BioNTech ended its partnership with Danish biopharma Genmab in pursuit of phase 3 trials for acasunlimab, a PD-L1x4-1BB bispecific antibody. Genmab is moving forward with further development on its own, the company said earlier this month. The drug is designed to elicit an anti-tumor response by activating 4-1BB on T cells and natural killer cells through simultaneous binding of the PD-L1 arm.

For well over a year, the FDA hasn’t granted any antibody-drug conjugate approval — the last one over the line was Immunogen’s Elahere for platinum-resistant ovarian cancer in November 2022. But the industry’s pipeline is set for more.

Over 80 ADC candidates are in phase 3 development, according to the healthcare management consulting and technology firm ZS.

In addition to treating a wide array of oncology targets — including breast, non-small cell lung, gastric and esophageal cancers — ADCs can be a less risky bet than other therapies. ZS estimates the probability of “technical and regulatory success” is 48% for ADCs currently in phase 3, compared to 41% for “oncology overall.”

This potential for patients and drugmakers has made ADCs one of the buzziest modalities in pharma and placed the technology at the heart of several big-ticket deals in recent years, including AbbVie’s $10 billion purchase of ImmunoGen and Pfizer’s $43 billion tie-up with Seagen.

While ADCs have already established ROI for many pharmas — ZS estimates global sales for the approved ADCs reached $7.5 billion in 2022 — there’s still a need to make them better. To boost outcomes and overcome lingering clinical challenges such as off-target toxicities, drugmakers are adjusting development strategies.

Some established leaders in the ADC space, such as Daiichi Sankyo, plan to test their drugs in combination with immunotherapy heavy-hitters like Merck & Co.’s Keytruda, while also working towards approvals in earlier lines of care.

Other developers are tinkering with the basic three components of ADCs — an antibody that hunts cancer cells, a cytotoxic payload that acts as a warhead and a linker molecule — to improve the technology. In a market that now includes most major players in pharma and a vast array of plucky upstarts, these emerging candidates have the potential to create longer lasting and less toxic therapies.

Here's how three rising companies in the ADC space are looking for an edge.

Genmab zeroes in on a novel linker tech

A long-time antibody specialist, Genmab is a natural fit for the ADC arena. In 2021, it snagged one if its first ADC wins when Tivdak, developed with Seagen, won an accelerated approval for metastatic cervical cancer. The ADC snagged a full nod in April based on phase 3 data showing it improved survival by 30% compared to chemo.

Genmab also deepened its commitment to developing ADCs this year through a $1.8 billion buyout of ProfoundBio. The deal will marry ProfoundBio’s ADC platform with Genmab’s antibody therapies and “suite of proprietary technology platforms.” The merger also pumped several assets into Genmab’s pipeline, including a phase 2 ADC called Rina-S.

Developed to treat ovarian cancer and other FRa-expressing tumors, the company believes its special sauce — a novel linker technology — will offer a favorable safety profile over rivals such as Elahere, which carries a boxed warning for numerous ocular toxicities, including some that are severe. 

“[Rina-S] is a second-generation ADC [with] a cleavable hydrophilic linker … this translates into none of the side effect profiles of the first ADCs,” Anthony Mancini, executive vice president and chief operating officer at Genmab, said. “With Rina-S, we’re not seeing ocular toxicities.”

As its ADC portfolio grows — the company has three candidates in the clinic including Rina-S — Mancini said Genmab is staking its claim in oncological women’s health.

“With Tivdak on the market for cervical cancer … we’re excited about Rina-S because these are two drugs in our target audience,” he said. “We think we can be a leader in gynecological cancer and differentiated in the market.”

Sutro Biopharma aims for multiple ADC breakthroughs

Sutro Biopharma’s lead asset luvelta could also become a competitor in the ovarian cancer landscape. In particular, the biotech aims to leverage the ADC in patients with “low to medium” levels of FRa expression, and won a fast track designation for the candidate, which is now in late-stage development for ovarian cancer, in 2021. 

But the company sees broad potential in indications including non-small cell lung cancer and other solid tumors. 

What sets Sutro’s approach apart from the rest of the field is that other ADCs use a “heterogenous mixture of molecules,” the company’s CEO, Bill Newell, said. 

“We started pioneering the notion that if you made a homogenous molecule, you could improve the medicines to be more beneficial to more patients and have less toxicity,” he said. “In the ADC field, that wasn’t possible when we started 13 years ago.” 

Sutro hasn’t indicated when it’s going to file for a luvelta approval, but if it hits the market, Newell said it’s targeting a patient pool of FRa-expressers in ovarian cancer that’s “more than double” that of Elahere.

And while it leads its own development for luvelta, the company has pulled together a string of partnerships for other pipeline hopefuls, including a $900 million deal with Ipsen to develop a preclinical ADC for solid tumors announced in April. 

The company also teamed up with Astellas Pharma in 2022 to advance immunostimulatory ADCs (iADCs), a potential breakthrough approach that Sutro said is “intended to deliver two different drugs directly to the tumor to not only kill tumor cells but also locally prime an immune response to the patient’s particular tumor cells.” 

Tubulis looks to payloads for a more durable ADC 

A spinoff born from two German academic institutions, Tubulis has set its sights on next-generation payloads.

The company has six assets in preclinical development for solid cancers and “one of the broadest platforms in the field right now,” according to chief scientific officer Jonas Helma-Smets.

Tubulis’ suite of platforms can “unlock novel payloads for the development of versatile and customizable ADCs,” the company said in a press release.

“We have a huge design space given by the technology in terms of drug-to-antibody ratio, different technologies to conjugate the antibody [and] we have novel technologies to explore other payloads,” he said.

Investors have been receptive to the idea. This spring, Tubulis raised $138.8 million to back pipeline development and “clinical proof of concept” for its two lead candidates.

As the company moves towards clinical trials, Helma-Smets said Tubulis’ technology could decrease the chances of off-target effects by “ensuring [it doesn’t] lose the payload,” while also creating a more durable treatment.  

“We’ve shown in preclinical animal models that we have a long-lasting effect in cancer-bearing mice, and that is a differentiating factor,” he said. “ADCs have done a good job of improving response rates, but we believe there’s still room for improvement. That durable response is what we hope to translate to the clinic.”

Pharma companies are on the edge of a looming patent cliff over the next several years, and generic competitors could topple sales of some of the industry’s best-selling drugs. For some Big Pharma companies, generics are already on the doorstep.

Bristol Myers Squibb could soon see some headwinds for its blockbuster leukemia drug Sprycel as the first generic is expected to hit the market in September.

Sprycel (dasatinib) is a kinase inhibitor that was approved in 2006 to treat chronic myeloid leukemia, a type of blood cancer that impacts 1 in 526 people in the U.S. The tablet has been a reliable blockbuster for BMS over the years, reaching $1.9 billion in sales in 2023, BMS reported in its latest quarterly update. Sales topped $2.1 billion in both 2022 and 2021.

BMS has faced several challenges to Sprycel’s patents, and filed a patent infringement lawsuit again Swedish biopharma company XSpray Pharma in 2022, as well as a handful of other companies that were challenging “two FDA Orange Book-listed monohydrate form patents expiring in 2025 and 2026,” the company said in a recent SEC filing.

BMS settled with XSpray last year, settling all pending litigation, but also paving the way for XSpray to launch a generic dasatinib as soon as Sept. 1, 2024. XSpray has previously billed itself as able to get around secondary patents before they expire thanks to its technology. The contested patents were not set to expire until Sept. 28, 2026. However, XSpray has a PDUFA date of July 31 for its “optimized version of dasatinib,” Dasynoc.

If Dasynoc is OK’d, it will join dozens of new generics approved across indications in 2024, including several cancer drugs. With this wave of generics, branded oncology treatments could see a price drop overall, according to IDP Analytics. 

There are more dasatinib generics in development from a handful of other pharma companies, including Biocon and Teva. 

What’s next for BMS

Amid the upcoming patent expirations and onslaught of generic competitors, BMS has kept its oncology pipeline warm with new candidates and also sought expansions for Sprycel — the FDA granted approval for Sprycel to treat pediatric patients with chronic CML in 2017

The pharma giant’s cancer drug Breyanzi, a one-time CAR-T cell therapy, won approval for large B-cell lymphoma in 2022, and the therapy has since seen expansions for patients with relapsed or refractory mantle cell lymphoma, as well as accelerated approval in May for those with chronic lymphocytic leukemia or small lymphocytic lymphoma. The FDA also granted accelerated approval of Breyanzi for follicular lymphoma the same month. However, BMS faces competition in the same therapy space from Gilead’s Yescarta.

Elsewhere in BMS’ pipeline are two candidates for acute myeloid leukemia in early clinical stages. AML is considered a hard-to-treat disease, and a drug developed by Celgene and picked up by BMS in 2019 when it acquired the company was approved in 2017 to treat the condition.

With an eye toward establishing itself as a standard bearer in blood cancer treatment, BeiGene is taking on some of the biggest blockbusters in the space with its next-generation BTK inhibitor Brukinsa, and building a bustling hematology franchise that can grow from there.

Brukinsa’s first FDA approval in 2019 for mantle cell lymphoma was the result of a robust research effort to improve upon Imbruvica from AbbVie and Johnson & Johnson and Calquence from AstraZeneca, said Dr. Mehrdad Mobasher, chief medical officer of hematology at BeiGene.

Four more approvals for the lead franchise drug followed, along with a growing pipeline that includes the BCL2 inhibitor sonrotoclax, now in a late-stage chronic lymphocytic leukemia study alongside Brukinsa, as well as a new modality called BTK degradation that seeks to permanently tear down the disease-causing proteins that Brukinsa inhibits.

While the increasing hematology competition and safety challenges have dogged sales for Imbruvica, which declined by about 20% last year, Brukinsa and Calquence have been on the upswing. Last year, Brukinsa’s global sales skyrocketed by 129% to $1.3 billion while Calquence hit $2.5 billion in revenues — a 22% bump.

Here, Mobasher discusses the approach that BeiGene is taking to build up its hematology franchise in a way that will cement the company’s spot in the blood cancer landscape and bring new treatments to the space that still has a tremendous amount of unmet need.

This interview has been edited for brevity and style.

PHARMAVOICE: What goes into shaping a portfolio in hematology that addresses unmet need and also establishes where you want to go in the long run?

DR. MEHRDAD MOBASHER: The way we do it is with a lot of emphasis on research. We have more than 1,000 researchers understanding the biology and developing cutting-edge models and processes from drug discovery to how we develop targets. With this giant research group, we have a lot of targets that come our way, and Brukinsa as a BTK inhibitor is an example of … where we will continue to have the best-in-class and first-in-class drugs. Sometimes, there are drugs out there, but they can become better — you can treat patients with the same targets in a better way.

Oftentimes, franchises like hematology and solid tumors can become siloed at a large company. How does BeiGene tie these pipelines together with a unified goal?

The simple answer is that we call it the BeiGene pipeline — not the solid tumor pipeline or the hematology pipeline. I oversee the development of assets in hematological malignancies, which is predominantly my background, and we have [chief medical officer] Dr. Mark Lanasa in solid tumors, and we share drugs, as well. The two organizations work very closely together but have clear roles and responsibilities in the diseases that each of us oversee.

What is the story of the BTK inhibitor class and how BeiGene got involved by bringing Brukinsa to the table?

From the beginning, the company designed Brukinsa purposefully to be successful where other BTK inhibitors weren’t. BTK inhibitors are known, and they’ve been out for a while. In fact, they’ve revolutionized the treatment of a lot of B cell malignancies. What they do is block what we call the B cell receptor signaling, which is important to have healthy, normal cells. When we control this signaling pathway, we control the survival of the malignant cells, putting them to sleep, which is what we’re trying to achieve. 

The first generation of BRK inhibitor was [Imbruvica from AbbVie and Johnson & Johnson], which was a really important step in the treatment landscape, and then the second generation was [Calquence from AstraZeneca], which improved safety. 

Then the next generation was Brukinsa, which we designed by understanding the science and optimizing the way we approach this target. Brukinsa was designed to be more potent and also very selective against BTK to avoid having off-target inhibition and toxicity. And that’s where the broad development plan allows Brukinsa to be successful in areas that other BTK inhibitors weren’t as successful.

How have you approached the development and expansion of Brukinsa that sets it apart from others in the class?

The broad development plan we took with Brukinsa eventually led to five indications in the U.S., which includes accelerated approvals like mantle cell lymphoma, marginal zone lymphoma and follicular lymphoma. The other two are chronic lymphocytic leukemia and Waldenström macroglobulinemia. It’s the only BTK inhibitor that has this broad label, and part of that bold plan was going head to head versus [Imbruvica], the first-in-class BTK inhibitor, in CLL patients, showing superiority in efficacy and safety — the only one to do so. Taking on big, broad, bold head-to-head studies is how we can show a deep and durable response.

You said that BeiGene’s approach allows you to take known pathways and improve upon them. How do you accomplish that?

When we look at the science, we understand the need of the targets and the molecules and how it can be improved. When you look at the names of our assets, they have a number after them, and that shows how many drugs were tested first before this drug was rolled out. The way we’re working is understanding the treatment landscape, the treatment evolution and the unmet need. We would like to cover the patient’s journey through these symptomological malignancies until we cure them. In the future, you’ll see more combinations of our own assets and combinations with important drugs that other companies make. In the near future, you’ll see more drugs in our hematology pipeline, as well.

Right now is “singularly, the most exciting moment” in Daiichi Sankyo’s 100-year history, said Ken Keller, CEO and president of the company’s U.S. business and head of its global oncology unit.

Riding high from the success of the AstraZeneca-partnered blockbuster cancer medication Enhertu, the company in October announced a partnership with Merck & Co. valued up to $22 billion. And with potential new approvals coming this year, Daiichi is on track to become a cancer powerhouse ahead of its own schedule.

Born from a 2005 merger between two long-standing Japanese pharmas — Sankyo Co. and Daiichi Pharmaceutical Co. — the company has been “cardio-centric” for most of its history, Keller said. Now the second largest pharma in Japan, its diversified portfolio also includes vaccines, migraine meds and more.

But Daiichi trained its eyes on oncology in 2020 when it launched Enhertu for HER2-positive unresectable or metastatic breast cancer, vowing to become a “top 10 cancer pharma company” within a decade. 

“That was a big ambition coming from zero,” Keller said. “Here we are, five years later, and we’ve changed how cancer is treated.”

The company’s special sauce is a proprietary antibody-drug conjugate platform called DXd it used to develop six candidates for multiple cancers. Since an original nod in breast cancer, Enhertu has racked up approvals for several other HER2-related indications, including the first tumor-agnostic approval for an ADC, which the FDA granted in April. 

Daiichi and AstraZeneca, its development and commercialization partner for Enhertu, also recently announced positive topline results from a phase 3 trial in patients with lower levels of the HER2 protein. The results, which the companies said showed a “statistically significant and clinically meaningful benefit” in progression-free survival, could help move the ADC into earlier lines of care.

Meanwhile, the company has three key PDUFA dates within nine months. This June, the FDA will render a decision on a HER3 treatment for non-small cell lung cancer that is now a part of its three-drug collaboration with Merck. The agency is also slated to announce decisions for a TROP2-directed ADC Daiichi is developing with AstraZeneca — first in NSCLC this December and then for breast cancer in January 2025.

If the approvals are granted, Keller said Daiichi will be poised to hit “top 10 cancer company status” by fiscal year 2026. 

It’s got plenty of competition. With ADCs becoming one of pharma’s hottest commodities, Pfizer scooped up ADC specialist Seagen in a $43 billion acquisition last year. But Daiichi is slated to dominate the ADC market through 2029 with the highest level of sales, according to analysis by GlobalData.

Here, Keller discusses growth prospects for Enhertu and how ADCs could one day become curative treatments in cancer care. 

This interview has been edited for brevity and style.

PHARMAVOICE: Sales for Enhertu more than doubled last year from about $1.25 billion in 2022 to $2.5 billion. Tell me about the long-term prospects for the drug.

KEN KELLER: Today we’re looking at five indications that we’ve received. We announced a positive pivotal trial, which would be another indication [and] a pretty amazing potential indication in the HER2 low space. The study looked at using it to displace chemotherapy rather than after chemotherapy, and we also demonstrated efficacy in the ultra-low HER2 setting. 

When you look at breast cancer, HER2 positive is about 20% of cases, HER2 low is about 50%, and including ultra-low means we can help close to 90% of women with breast cancer. It would be the biggest drug ever in breast cancer. That gives you a sense of where the program is going. 

Enhertu has been massive for Daiichi, but is the company relying too heavily on this single drug for future growth?

Enhertu is the foundation of everything we’re doing. Today we’ve got the ADCs we’re developing with Merck and AstraZeneca, we have two other DXd treatments in the clinic and we are leveraging our leadership in ADCs. So, we’ve got second and third generations of treatments we’re working on right now.

We’ve got a decade of clear growth, and hopefully our technology continues to grow and improve.

Do you see any new, big partnerships on the horizon? 

It’s going to come down to the specific molecule or ADC we’re talking about. If we have a drug that we think has just a few indications, we can do that ourselves. If we have a drug that we think can be used across a dozen different cancers, that’s when we think about how we can develop it as fast as we can, and get it to as many patients as we can. 

I’ve been here about 10 years and was the first employee of the oncology unit. Back in 2015, we had one oncologist — today we have over 2,000 people in the oncology part of our business. We are much more capable today, but we know we have to be open to working with others.  

One of the biggest criticisms of emerging technologies in oncology is that pharma companies are making blockbusters out of drugs that only add months to patients’ lives. Do you have development efforts underway aimed at improving outcomes for ADCs?

This is what makes this DXd platform so unique. In our first indication [for Enhertu] we compared it to Kadcyle from Genentech, and we didn’t add months to survival — we added years. In second-line breast cancer, we added 28 months of progression-free survival compared to six.

When I look at starting an oncology franchise within a company, you couldn’t find a more profoundly beneficial drug. But two things are going to make a difference going forward.

We are going to move into early-stage disease and catch it earlier with a potent drug.

The second is moving into a combination setting with immuno-oncology treatments like Keytruda. We started in late-stage as a monotherapy, and as we move earlier and look at the power of ADCs and immuno-oncology, we think that could change things. 

In the earlier stage and in the adjuvant or near adjuvant setting, a cure is the goal.

Among the strategies Big Pharma is employing to achieve more equitable health outcomes, AI is now playing a larger role. For AstraZeneca, a series of AI-based partnerships and screening initiatives is setting the stage to gather and use data for cancer patients in neglected ZIP codes.

As it stands, innovation is outpacing health equity, widening the gap in oncology between patients who have access to novel medicines and those who do not, said AstraZeneca’s senior vice president and head of U.S. oncology Mohit Manrao.

Black Americans have higher death rates than any other racial group for many cancer types, according to the NIH’s National Cancer Institute. Furthermore, people without access to healthcare are more likely to be diagnosed later in their disease trajectory, putting them at greater risk of death.

“Science is moving so fast, but the job isn’t done after that,” Manrao said. “The challenge we have at a local level is that disparities are increasing, and more and more people fall through the cracks. Everyone in the system has good intent, but it’s important that as an industry, we embrace opportunities and collaborate to solve for it.”

AI is one of the most promising opportunities for improved health equity, Manrao said. By teaming up with diagnostic makers and AI companies, AstraZeneca wants to use data to expose the disparities in care, and address screening and access issues that exacerbate them. Manrao said AstraZeneca’s mission goes beyond developing oncology meds like the blockbuster Enhertu, which was originally approved for breast cancer in 2019 and recently scored a new expanded indication, and AI can find patients who need it.

“There is no reason that a Black woman with breast cancer in New York should have different outcomes than a white woman living in California or Atlanta — the ZIP code lottery exists today,” Manrao said.

Here, Manrao discusses the effect data-driven AI can have on the understanding and mitigating disparities in cancer care, the partnerships AstraZeneca has sought to bring AI into the fold, and how the feedback loop will also help drive better R&D for more equitable outcomes down the road.

This interview has been edited for brevity and style.

PHARMAVOICE: How do you characterize the impact that AI can have on patients, particularly from a health equity standpoint?

MOHIT MANRAO: Availability of data has multiplied in a multitude of ways, both in terms of genomic data and multi-omics data at a patient level and a customer engagement level.  Similarly, science, technology and data are converging very quickly, and that helps us believe we can have an impact on patients at every level. From a health equity lens, beyond our bread and butter in biopharmaceutical innovation, we want to start looking at the entire patient pathway and ask new questions. Are patients getting screened? What are the risk factors? Are they going to screening centers? Are they followed up appropriately in the system at the right intervals to be detected early?

Because of the socio-economic determinants of health, we need to have individualized interventions to solve for specific barriers that get in the way of a specific patient.

Because AI is trained using past examples, bias often finds its way into algorithms. How do you advance AI so that it can actually introduce progress rather than remain with the status quo?

It’s a super important point. Being aware of bias that would get into a system and putting checks and balances around it can help us look at health equity. Across the pharmaceutical value chain, it starts with inclusive R&D. We have drugs that get developed based on biosamples, and we’re working on creating diverse biosamples that are representative of the populations we serve. Of course, we can’t do that alone. So working at a local grassroots and community level to bring those diverse biosamples into drug development helps ensure that patient recruitment meets those goals. 

For instance, at a clinical trial centered in a community in New Jersey that is 18% Black, we work with them to ensure that not only 18% is recruited from that community, but more so that we can help dig and gather data. And all this serves to help AI predict without bias.

Your AI strategy has been heavily partner-focused. How does a potential partner stand out within the AI boom?

When ChatGPT came out, it exploded into the world in a visible way, but we have been using AI in different parts of the value chain already. We have more than 700 data scientists who are AI experts working in different parts of our organization from early drug discovery to development to commercial organizations and operations. We’ve embedded them to think in terms of looking for partnerships — we can’t move forward alone. So looking at the right partners with the capabilities, values and vision in terms of transforming cancer care is very critical. For example, in early detection, there are a multitude of challenges. If we see that tissue-based screening is a challenge, we work with blood-based companies to look at how we can help improve their assay. That led us to work with Grail in that space. 

Companies like Qure.ai can use technology to find lung nodules on X-rays that a naked eye couldn’t see, and companies like Clinithink have natural language processing that can go into electronic medical records. These are all important steps.

At the same time, let’s take the example of lung cancer — screening has been approved in the U.S. since 2013 and even a decade later, the uptake is dismal at only 5% to 6%. Socio-economic determinants are a barrier to lung cancer screening, and we’ve worked with the Association of Cancer Care Centers to understand and work with local communities, and use that rich data to inform where the pockets are, such as a rural Appalachian screening program for lung cancer in Kentucky. 

Similarly, we just announced a partnership with the University of Maryland system across counties in the state to identify at-risk populations. These academic and community institutes play a big part in the data-gathering process.

As you collect data, how does that feed back into the drug discovery and development process?

It’s critical that we put patients at the heart of drug discovery and development. All this data, in many ways, unlocks opportunities to uncover true unmet needs for patients, and the bigger picture is we want to eliminate cancer as a cause of death. Understanding through these datasets why the disease is progressing and informing R&D by identifying patients earlier. The partnership with Grail, for instance, helps us not only identify patients but also to look at the data and [see] which patients within this group are high-risk and the kinds of interventions they need. So this is integrated across the internal value chain.

The secret sauce for us, and it’s not truly secret, is external collaboration. We don’t shy away from partnering with the right party. What stands out for us and for anybody who wants to move the needle for patients is that we can’t work in silos.