Learn about promising drugs currently in the pharmaceutical pipeline and the impact of FDA interventions from presenters at AMCP 2024.  

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Jeffrey Casberg: I’m Jeff Casberg. I'm a pharmacist and I’ve been in managed care pharmacy for over 25 years. I've worked in pharmacy all over, starting in retail before moving into pharmaceutical sales, hospital pharmacy, home infusion, PBMs, and health plans. I guess it sounds like I can't keep a job, but I've worked in managed care between just 3 organizations for the last 25 years or so.

Leslie Fish: And I am Leslie Fish. Just like Jeff, I am senior vice president in the pharmacy at IPD Analytics. I started off in hospital pharmacy, and I practiced pediatric oncology at the New England Medical Center. I then went into managed care for 25 years, and I've been at IPD for a little over 8 years.

Could you provide an overview of the most promising brand-name drugs currently moving through the pharmaceutical pipeline? 

Leslie Fish: First of all, one of the things that interests me about this question is that when we talk about promising drugs, there has to be a qualification. It must be a blockbuster medication that is well-utilized and highly impactful in terms of costs and revenues or utilization. 

I’ll share some of the top medications I think could be impactful. Almost 40% or so of pipeline medications are in the oncology space, but a lot of them are just another piece in the overall “pie” of oncology but they aren’t the most important pieces of the pie. But there are two areas that we think could be more important. 

One part is that we recently had a medication approved for gliomas. There aren’t a lot of medications in the pipeline for gliomas becausne often it is a pediatric adolescent disease. The second area of interest is tarlatamab for small cell lung cancer. There are many medications for non-small cell lung cancer but very few for small cell. The approval of tarlatamab could be impactful for oncology. The area of pulmonary hypertension is also quite busy. Sotatercept (brand name Winrevair) was recently approved and could shake up the utilization in pulmonary arterial hypertension (PAH). 

Jumping back to the oncology space, we're seeing CAR T used earlier in therapy. So already approved medication like CAR T may start aiming to be an added indication, such as a second line therapy, and that could be very impactful. KarXT for schizophrenia is also showing promise. A lot is development in the adult vaccine space for RSV. They’re looking at younger populations, such as 50 to 59-year-olds. One of the manufacturers even claim they have data on a lower range such as 18 to 59-year-olds. Depending on what happens they could really shake up the market because that would encompass most of the population. Finally, there is an mRNA RSV vaccine from Moderna that actually could be approved this year, too. 

It's important to not only recognize new pipeline medications, but also new supplemental indications, whether they be sNDAs for small molecule or biologic sBLAs. One great example was a drug called Livmarli originally approved for Alagille syndrome that recently also became FDA-approved for pruritus and progressive familial intrahepatic cholestasis.

Jeffrey Casberg: Since we presented on both specialty and traditional drugs at AMCP, I want to touch on 3 drugs that treat non-alcoholic steatohepatitis (NASH) and metabolic dysfunction-associated steatohepatitis (or MASH), Alzheimer disease, and then schizophrenia. 

First, Rezdiffr (resmetirom) from Madrigal Pharmaceuticals is the first FDA-approved drug for NASH/MASH. There were a few that almost made it to market, but this once-daily product that reduces liver fat and inflammation is the first as of March. Phase 3 MAESTRO-NASH studies for NASH resolution and fibrosis improvement showed positive results. The drug is also unique because it has potential cardiovascular benefits due to reduced LDL cholesterol. Another key point about this drug is that previous drugs coming down the pipeline had side effect profiles that were intolerable, but Rezdiffr looks to have a pretty clean tolerability and side effect profile. It also gained accelerated approval based on surrogate markers, so there could be future studies coming up. The drug costs about $48,000 per year, which was about what IPD analytics was anticipating.

The second high-impact item I want to discuss is Donanemab by Eli Lilly Pharmaceuticals for treating Alzheimer disease. It's a beta-amyloid product, not too different than the Eastside Biogen product Leqembi except that donanemab is a professionally administered IV done once monthly as opposed to every 2 weeks for Leqembi. Donanemab is not quite approved yet and has had a storied path to approval. It was supposed to be approved a year ago and has had some delays but the FDA has requested an advisory board meeting for June. If their review is positive, approval could be announced in the second half of 2024. IPD anticipates a similar price to Leqembi. 

The last drug I want to mention is KarXT by Karuna or BMS Pharmaceuticals. XT are the first initials of the two drugs in the combination drug, xanomeline and trospium. Xanomeline is the active ingredient, it's a muscarinic agonist. They found it was causing some unwanted side effects and added in trospium that is a muscarinic antagonist that offsets the side effect profile. Many medications for schizophrenia have the side effect of weight gain, but Olanzapine seems to not. It has a prescription drug user fee act (PDUFA) date this fall and we anticipate a $20-30,000 price tag. 

How do you foresee potential FDA or litigation delays impacting the projected time to market for these upcoming drugs? 

Leslie Fish: It's a great question and one of the things we have seen rumblings of for a long time are patent tickets. Patent tickets are when pharmaceutical companies add patents to existing products. It may start with one patent, but you may end up with a drug such as Humira, which has 100 patents. Some could be strong patents, but others could be very weak. This approach is an attempt to extend the life of the branded product before it becomes a biosimilar or generic. 

The FDA advisory committees are also interesting. There are a lot of medications that have gained accelerated approval through surrogate markers instead of endpoints. For example, in osteoporosis, a surrogate marker will be bone density when what you're really looking for is fracture rates. That being said, the FDA advisory board committees appear like to be trying to utilize more than just the surrogate data. For example in oncology, even though there are surrogate markers such as progression-free survival and durability, the FDA seems to also want to see overall survival. Over the last few years, there have been a lot of confirmatory trials and it's going to be very interesting to see what the FDA does about that.

One last thing, the FDA is looking at designated interchangeability for biosimilars and this could increase cost effectiveness. Right now there are certain rules on how a biosimilar can get an exclusivity period and what the FDA has proposed is taking away the designation of interchangeability. 

Jeffrey Casberg: The drugs I’ve spoken of have a number of these elements. Denamoub is a high-impact potential approval and the FDA has actually had a pretty strong hand in controlling its path to approval. Back in January 2023, we were looking for approval a year ago. But the FDA issued a CRL, a complete response letter, because they found some issues with the phase three study. For the most part, pharmaceutical manufacturers don't like CRLs. If you get a CRL, that usually means additional time and expense to get your drug to market. But the FDA uses that to make sure that the drugs that come to market are safe and efficacious. After that, the FDA delayed approval again when they requested an advisory committee meeting. 

The FDA impacted Rezdiffr (resmetirom) when they issued an accelerated approval. Accelerated approval can be granted based on surrogate endpoints even if the phase three studies aren't completed if there's a need in that therapeutic category for treatments.

What are key considerations for pharmacy and therapeutic committees when evaluating the value and role of new drugs and therapies?

Leslie Fish: What P&T committees are doing now is going back to the basics more than we've ever seen before. Just like the advisory board committee meetings, they're not only looking at the statistical significance but also clinical significance. What are the real outcomes of this? They want real data. Manufacturers are being asked what this means more clinically than statistically. In oncology, something may look great statistically such as an increased lifespan by 75%, but then you find out that the patient did not feel good during that extra time. 

Second, P&T committees are under the gun even more than before. I never thought it could get any more dire in a way, but because of the number and cost of these new products, especially for rare diseases, they are becoming stricter. They're looking at excluding drugs or limiting formularies. They’re asking, “How do we put in step therapies that are appropriate for the right patient at the right time for the right disease in a real cost-effective manner?”

Jeffrey Casberg: I'm thinking along the same path, Leslie. Our company, IPD Analytics, sets out to find the key considerations for P&T committees when evaluating drug management. Nowadays, as Leslie alluded to, there's more pressure to tightly manage drugs, especially with the IRA coming down the road. Instead of just looking at safety, costs, and efficacy. To spend those pharmaceutical dollars most efficiently, they're going to have to consider prior authorization criteria. I think P&T committees have a tougher job today than they did many years ago.

Which indications do you see as most promising in the drug pipeline? 

Leslie Fish: There are several relevant examples from the rare disease space. WHIMs disease recently got an approval. Niemann-Pick disease type C disease has a medication that could get approval as well as 2-3 others in the pipeline. Galactosemia, as well. For atopic dermatitis, the medication nemolizumab can be used in conjunction with the topicals. It is also now indicated for prurigo nodularis. In dermatology, there is a promising gene therapy for recessive dystrophic epidermolysis bullosa, a condition where lesions form all over the body. A gene therapy for it is prademagene zamikeracel. 

In the hemophilia space Roctavian for hemophilia A was approved back in 2023. There also was Hemgenix for hemophilia B approved in 2022 and very recently, Beqvez was approved. Hematologists themselves are not jumping to put people on gene therapy if the patient is stable, especially if they're stable on a long-acting factor such as factor 8 or 9, depending on which hemophilia you have. Hematologists want to see more about durability, side effects, and side effect potential.

Likewise, in a disease called beta thalassemia, there is gene therapy. For sickle cell disease, just this year it was announced that the first 14-year-old boy is receiving gene therapy. There also is a lot in development for paroxysmal nocturnal hemoglobinuria (PNH). 

Jeffrey Casberg: I'm going to go down a different path focusing less on specific drugs. I think the most important approvals coming down the road are generic and biosimilar approvals, not brand approvals.

On the generic side, there are a lot of drugs nowadays that may have slight advantages or slight dosing differences or methods of administration. But the previous drug that was approved 10 years ago, it's pretty good. I think from a managed care and cost perspective, tight management of step therapy with generics will be important coming up for the payers, again, trying to be as tight on formulary management as possible. 

On the biosimilar side, we're finally starting to see a crack in the door with some of the big PBMs and payers moving from Humera to focus on biosimilars. I think we're going to start seeing that more and more in the coming years. 

Leslie Fish: We can’t talk about the pipeline without at least mentioning weight loss medications. We don't know what's going to happen with weight loss medications yet, but we are beginning to see insurers talk about how to manage these expensive medications. There are a lot of people in the United States who qualify, especially as new indications emerge for the heart, not just diabetes. 

Jeffrey Casberg: In 2024, we're going to see the GLP-1 Victoza become generically available. There will be multiple generic versions available around mid-year. It's a once-a-day injectable so I'm not anticipating big cost savings opportunities or the ability of this drug to alleviate the issue of the shortage because most people aren’t interested in a daily injection. On the weight loss side, Victoza only has about 50% of the weight loss capacity of a GLP-1 like Ozempic. Trulicity is also a biologic coming up in 2027. Ozempic is a traditional pharmaceutical, not biologic. So it will be a generic drug, not a biosimilar, that'll come around in 2030 or 2031 for Ozempic.