Drug pipeline insights: Treatments poised to make an impact

Scott Draeger: The drug development pipeline is such a broad topic. Sara, to help channel this discussion, can you perhaps identify a few drug classes or overall trends you see that are having an outsized impact in 2025?

Sara Guidry: Absolutely, Scott.  So, starting at a high level, it's really no surprise that the three biggest categories or classes that are driving both trend and net spend are:

• Chronic inflammatory
• Oncology
• GLP-1s 

Those are three categories that I think everybody's been hearing a lot about. For the GLP-1 drugs, trend is due to increased utilization for both diabetes treatment and their use for weight loss. For chronic inflammatory and oncology, this is mostly a reflection of newer, sometimes more expensive drugs becoming available and continued gradual growth for existing drugs.

Scott: Any discussion of prescription drugs in 2025 will eventually come around to the GLP-1 class. Arash, as our GLP-1 pipeline expert, can you level-set where this class is now in terms of both new indications for existing drugs as well as potential new market entrants? 

Arash Sadeghi: What's interesting is that there has not been a new GLP-1 approved since the end of 2023 with the approval of tirzepatide or Zepbound® for weight loss. But what has evolved in the last two years has been the data around these drugs and the growing number of FDA-approved indications — some of which address conditions where GLPs have not been used in the past. The most notable and probably most important of these indications came last year in March of 2024 when Wegovy® became the first weight loss drug approved for a cardiovascular indication – specifically to reduce the risk of major cardiovascular events.

In the last 12 months we’ve also seen the approval of semaglutide or tirzepatide for sleep apnea to chronic kidney disease to most recently, metabolic-dysfunction associated steatohepatitis or MASH, which is a common liver disease. All of these are highly prevalent conditions, although overlapping with obesity or type 2 diabetes.

In late August, we did get some competition in this category with the launch of the first generic GLP-1 drug indicated for weight loss. This was liraglutide, which is the generic for Saxenda. It is noteworthy that we finally got a generic in this category for weight loss, but important to keep in mind that Saxenda® has been the least utilized weight loss GLP-1 drug, and it provides numerically less weight loss on average compared to the newer generation of GLP-1 drugs.

Looking ahead at the pipeline, the biggest near-term development in the class are oral drugs for weight loss. An oral formulation of Novo Nordisk’s Wegovy could be approved in the fourth quarter, and that would be the first oral GLP-1 drug approved specifically for weight loss. Eli Lilly also has an oral product, orforglipron, which could be approved by late 2026. 

These drugs are going to provide an oral alternative for some patients who may have been reluctant to use injectable GLP-1 drugs particularly for weight loss. But I will say we do not think these drugs are going to be paradigm shifting in terms of the magnitude of weight loss or tolerability relative to injectables, and for that reason these oral drugs will likely have a modest impact in terms of overall utilization for the GLP-1 category.

Scott: One of the things that strikes anyone looking at the pipeline is just how many oncological medications are under development. Sara, how is this profusion of drugs shaping cancer care and costs related to it? 

Sara: Great question. First, for context, oncology is the largest therapeutic category in the pipeline and has been for many years. In fact, about 15% to 20% of novel drugs approved annually are for a cancer indication. 

From a cancer care perspective, the good news is that cancer death rates over the last 30 years have been steadily declining. In fact, from 2013-2022, the mortality rate for cancer dropped by ~1.7% annually. This is due to a combination of factors, including increased screenings and earlier detection, as well as a huge contribution from advancements in cancer treatment. Where historically the only medication option was chemotherapy, we now have targeted therapies and immunotherapies. 

Some might be wondering — what’s the difference? In general, chemotherapy works by killing rapidly growing cells, while targeted therapies interfere with the specific proteins that cancer cells need to grow. Immunotherapy uses the patient’s immune system to attack the cancer cells. So, treatments are getting more specific and are providing more effective options.

Connecting the dots with all of this, while overall utilization of cancer medications has been generally steady, we are still seeing an increase in spending trend for this class. That trend is mostly driven by utilization shifting to the newer therapies that are often more expensive than historical standards of care (such as chemotherapy, as mentioned). In addition, in some cases, the newer therapies are used as add-on therapy rather than being an alternative treatment. 

Lastly, we now have treatment options for some patients who previously had untreatable cancers. Cancer care is so complex and will likely get more complex with the large number of pipeline drugs still to come. As innovation continues in this space, the challenge will be balancing clinical benefit, affordability, and sustainability across an increasingly intricate treatment landscape.

Scott: You mentioned affordability. One of the things that’s helped counteract the cost of all these expensive new drugs is the arrival of biosimilars. This has certainly been the case in the inflammatory category. Are we seeing biosimilars make a similar impact in other places like oncology?

Sara: You are so right about the inflammatory category — the biggest biosimilar launches to date have been in that space, with the most impactful ones being Humira last year and Stelara this year. There have been biosimilars for other blockbuster drugs across different diseases but nothing as significant as those two. One recent example is Prolia for osteoporosis.

But for oncology specifically, we’ve only had three cancer treatments with biosimilar competition – Avastin, Herceptin, and Rituxan. All of these saw first-time biosimilar approvals back in 2017-2018. This isn’t all that surprising because we need to keep in mind that many of the biggest oncology drugs are not biologics, but are more traditional, smaller molecule drugs, where we have seen some generic competition. There is, however, an interesting story when we look at the biosimilar pipeline for oncology. We have to look further out, but if we look to 2028, there is a potential for biosimilar launches for Keytruda and Opdivo.

As we are years away, this is based on patent expirations as opposed to any filings at this point. Keytruda and Opdivo are both indicated to treat a variety of types of cancer and in a class of drugs called immune checkpoint inhibitors that are primarily paid through the medical benefit. Keytruda’s 2024 U.S. total sales were approximately $20B while Opdivo’s were $6.4B. The interesting story with these two products is that the biosimilar pipeline for 2028 is specific to the intravenous formulations of these products. Both Keytruda and Opdivo are now available in subcutaneous formulations, with Keytruda’s subcutaneous form just being approved in September. While the subcutaneous formulations are still medical benefit, they offer more convenient and shorter infusion times. So, for these products, we are anticipating prescribing patterns to shift to those subcutaneous versions prior to the IV biosimilars becoming available. 

There are always many factors when we consider the impact of the pipeline. Overall, for oncology medications, generics and biosimilars alone have not been enough to stop trend because of the influx of new drugs and new formulations.

Scott: Let’s wrap up by looking ahead. Arash, is there anything that you are tracking for 2026 or beyond that plan sponsors need to be aware of? 

Arash: Alzheimer’s disease is an area to watch the rest of this year and into next year. This is a disease where there is still a significant unmet need both for treatments of the actual condition and the comorbidities that often come with Alzheimer’s that can also be a challenge from a treatment perspective. So, over the next 12 months or so we’re monitoring three key data points or catalyst events.

The first one of these is going back to the GLP1-s, we’re expecting data for semaglutide to be presented for Alzheimer’s disease treatment in December at the Clinical Trials on Alzheimer’s Disease Conference, which is a major conference when it comes to Alzheimer’s. That will be an interesting study because if the results are positive, it would be a new population eligible for treatment with GLP-1 drugs.

The second one is around the anti-amyloid targeted therapies. These drugs had been IV infused products that had to be administered by a healthcare provider, but just recently we got the approval of a subcutaneous, self-administered formulation of Leqembi, which is one of the drugs in this class. That formulation was approved in August for maintenance therapy but only after patients finish 18 months of IV treatment, so there is still a barrier there. Next year, it’s possible we’ll get the approval of that self-administered formulation of Leqembi for treatment initiation so patients could potentially bypass the IV product altogether, and we think that could have an impact on utilization because of improved access.

The last key drug is Cobenfy®, a novel antipsychotic that was approved for schizophrenia at the end of 2024 and it’s currently being evaluated for Alzheimer’s disease psychosis. The first set of data for this indication is expected later this year. This is important because no other drug is approved for this specific use and it’s an area of unmet need since current options, which are traditional atypical antipsychotics, have a boxed warning for increased mortality in elderly patients with dementia-related psychosis. If the data for Cobenfy are positive, it could serve as a safer alternative to the existing standards of care.

And going back to your original question about why plan sponsors should care about this – it’s because even though these are all drugs that are currently on the market already, if the data is positive and these drugs get these new expanded uses, it could have a significant impact on utilization of these drugs and overall drug spend for patients with Alzheimer’s disease.

Scott: Same question for you, Sara. Anything on the horizon that you are keeping a close eye on?

Sara: Scott, we've talked about so much, but there's always something more. Another one that we're watching is dyslipidemia. It's an interesting area because there are several novel drugs across different indications potentially that will be coming over the next couple of years.

The most interesting drug and trial in the category is likely pelacarsen for elevated lipoprotein(a). This is a form of cholesterol that doesn’t have any treatment options today. In fact, the trial, HORIZON, is the first study of its kind evaluating the link between reducing lipoprotein(a) and cardiovascular outcomes. This is one to watch as elevated lipoprotein(a) is very common in the U.S., affecting about one in five adults.

As far as anything else on the horizon — I mentioned there is always more, but I think as it stands everything we touched on today is most important in this moment. Happy to be here to help highlight these areas and hopefully bring a better understanding to the audience. 

Scott: Sara and Arash. Thanks for your time and insights today.

Sara: Thank You, Scott.

Arash: Thanks, Scott.