Reprinted with AIS Health permission from the October 2023 issue of Radar on Specialty Pharmacy
The specialty drug landscape continues to be a dynamic space, as new agents enter the market and existing ones gain FDA approval for additional indications. Global health care and specialty pharmacy solutions organization AscellaHealth recently released its quarterly breakdown of insights into treatments within the segment.
The Q3 2023 Specialty & Rare Pipeline Digest examines new approvals and launches of specialty drugs, including biosimilars, generics, and cell and gene therapies, as well as ones in the pipeline.
Among the highlighted agents in the recently released report were Alzheimer’s disease drug Leqembi (lecanemab-irmb) from Eisai Inc. and Biogen, myasthenia gravis therapy Rystiggo (rozanolixizumab-noli) from UCB, Inc. and Pfizer Inc.’s alopecia areata medication Litfulo (ritlecitinib).
It also scrutinizes drugs with upcoming FDA decision dates, including bluebird bio, Inc.’s sickle cell disease gene therapy lovotibeglogene autotemcel and Rocket Pharmaceuticals, Inc.’s gene therapy marnetegragene autotemcel for the treatment of Fanconi anemia.
AIS Health, a division of MMIT, spoke with Andy Szczotka, Pharm.D., chief pharmacy officer at AscellaHealth, about some of the report’s findings. The following interview has been edited for length and clarity.
AIS Health: Which of the recently approved agents holds the most promise, and why?
Szczotka: Many of the recently approved agents hold promise for advancing treatment options for their respective therapy areas. Two therapies that hold interesting promise in advancing therapy include Veozah and Elevidys.
Veozah is a neurokinin 3 (NK3) receptor antagonist…indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. The most common symptom during the menopause transition is hot flashes, [which] occur in up to 80% of women. Traditional treatment of moderate to severe hot flashes can include hormonal therapy, SSRIs, SNRIs, anti-epileptics, clonidine, oxybutynin and centrally acting drugs. Veozah is a different, non-hormonal approach for the treatment, and the clinical trials demonstrated a statistically significant reduction from baseline in the frequency of moderate to severe vasomotor symptoms. In a January 2023 report, ICER [Institute for Clinical and Economic Review] stated that it appears promising in the treatment of vasomotor symptoms, but longer-term safety and efficacy data are needed.…Comparative studies will be needed to determine its role compared to hormone and other non-hormone therapy options for vasomotor symptoms.
Elevidys is the first FDA gene therapy for the treatment of pediatric patients 4 through 5 years of age with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the dystrophin gene. Most current approaches to treatment of DMD address the symptoms of the disease but not the underlying genetic cause. Given that Elevidys is the first gene therapy for DMD, it provides a different approach and option in the treatment of the disease by targeting the underlying genetic issue rather than symptom management, especially in those patients who are not eligible for exon-skipping RNA therapies.…
Gene therapy for the treatment of DMD has always been difficult due to the large size of the DMD gene encoding the dystrophin protein. Elevidys is different in that it delivers an engineered micro-dystrophin gene to the muscle cells in order to produce dystrophin.…
Additional long-term data is needed to confirm its efficacy, but it seems to hold promise in the course of treatment of DMD in this specific age group of children [ages 4 to 5 years old].
AIS Health: Assuming Bimzelx (bimekizumab) is approved, why might the Humira biosimilars negatively impact its uptake?
Szczotka: If approved, Bimzelx would be another available therapy option for the treatment of plaque psoriasis. Adalimumab is one of many agents that also has FDA approval for the treatment of plaque psoriasis. Adalimumab biosimilars could negatively impact the uptake of Bimzelx since these agents can be used for the treatment of plaque psoriasis at a significantly reduced cost compared to an expected cost for Bimzelx.
In a published study of 478 patients comparing adalimumab to bimekizumab in patients with plaque psoriasis, the study authors concluded that bimekizumab was noninferior and superior to adalimumab with respect to a PASI 90 response and an IGA score of 0 or 1 at week 16 in patients with plaque psoriasis. By week four, a higher percentage of patients receiving bimekizumab had a PASI 75 response than patients receiving adalimumab but was associated with a higher frequency of oral candidiasis and diarrhea.
The authors recommended that longer and larger trials are required to determine the efficacy and safety of bimekizumab as compared with other agents in the treatment of plaque psoriasis. Without conclusive evidence showing significant clinical or safety advantages and the many therapy options available for the treatment of plaque psoriasis, payers would likely utilize other proven, lower cost agents, including adalimumab, for patients as compared to a newer agent without more conclusive, long-term safety and efficacy data available.
AIS Health: How do the two Duchenne muscular dystrophy (DMD) pipeline drugs compare with treatments currently available?
Szczotka: DMD is typically managed with corticosteroids like deflazacort and prednisone. The purpose of utilizing these steroids is to reduce inflammation and strengthen muscles; however, these steroids have a number of side effects, including high blood pressure and fluid retention, among others. Vamorolone (VBP15) is a dissociative steroid. It works in a similar way to corticosteroids in that it inhibits certain pathways, such as the NF-kB pathway, which is linked to inflammation. Additionally, it stabilizes membranes around the cells without causing what is known as transactivation. Transactivation is the increase of gene expression that glucocorticoids cause, which results in many of the side effects seen with glucocorticoids. Therefore, fewer side effects are seen with vamorolone compared with the corticosteroids currently used in treatment of DMD.
Givinostat is an HDAC inhibitor that blocks histone deacetylases (HDACs), which are involved in turning genes “on” and “off” within cells and can reduce muscle regeneration in DMD. By inhibiting this activity, givinostat may be able to activate muscle repair mechanisms to increase muscle fiber regeneration and reduce inflammation. If approved, givinostat would be the first HDAC inhibitor indicated for the treatment of DMD, and it would be an additional treatment option to target inflammation in DMD. Other treatment options for DMD include the antisense oligonucleotides, Exondys-51, Vyondys 53, Viltepso, Amondys 45, and a gene therapy, Elevidys; however, none of the current available agents inhibit HDAC.
Unfortunately, no direct head-to-head comparison studies are available for the newer DMD treatment options, so comparisons will be left to interpreting the available studies and for the specific DMD subtypes.
AIS Health: Do any of the drugs with upcoming FDA review dates offer potential improvements over currently available treatments?
Szczotka: Love-cell and exa-cell will be the first gene therapies available for sickle-cell disease. Lovo-cel is an investigational one-time gene therapy designed to add functional copies of a modified form of the faulty gene into a patient’s stem cells, which ultimately reduces the number of sickled red blood cells. Lovo-cel has been shown to sustain levels of healthy red blood cells and reduce the frequency or eliminate acute episodes of severe pain and organ damage. Current available treatments include agents used in the management of symptoms, to lower the frequency of the disease and to manage acute pain.
Exa-cel is another experimental gene editing therapy for sickle-cell disease (as well as beta-thalassemia). With exa-cel, a patient’s blood cell precursors are isolated and genetically modified to make high levels of fetal hemoglobin, a form of hemoglobin produced during fetal development that is more effective at carrying oxygen than its adult counterpart. These cells are then expected to populate the blood with healthy hemoglobin-producing blood cells. Both of these agents may offer improvements over currently available treatments due to the targeted mechanism of action and the only curative treatment currently available for sickle-cell disease is a bone marrow transplant.
AIS Health: Do any of the drugs with upcoming FDA review dates target a condition that does not have any current treatments?
Szczotka: RP-L102 (marnetegragene autotemcel), an investigational gene therapy for the treatment of Fanconi anemia, contains patient-derived stem cells that have been genetically modified and infused back into the patient with the goal of preventing bone marrow failure. Fanconi anemia is a rare and serious inherited blood disorder that leads to bone marrow failure. It prevents bone marrow from making enough new blood cells, and, if given early in life, it has the potential to serve as a preventative measure, correcting bone marrow cells well before bone marrow failure. Currently, the only treatment available for Fanconi anemia is stem cell transplantation, which is associated with significant toxicities and complications, such as graft vs. host disease.
AIS Health: There are many hematologic gene therapies with upcoming reviews. Why does that trend exist? Are gene therapies inherently more effective than “traditional” specialty drugs?
Szczotka: Hematologic diseases, which are disorders of the blood and blood-forming organs, afflict millions of Americans.…For several of these diseases, a specific genetic defect has been identified as well as a corresponding way to correct the defect.
Prior to these discoveries and treatment options, hemophilia patients required frequent prophylactic infusions up to several times per week to reduce joint bleeding events, prevent life-threatening bleeds and help to preserve joint functions. Unfortunately, even with strict lifelong prophylactic infusion schedules, spontaneous bleeding or unobservable yet harmful micro-bleeds can still occur. Prophylactic infusions are also very expensive and can cost approximately $550,000 to $750,000 annually.
One-time gene therapy can be extremely expensive as well, with costs often ranging between $2.8 and $3.5 million dollars. However, lifetime costs for ongoing routine prophylactic treatment can reach as high as $20 million. The ability of these hemophilia gene therapies at preventing the need for long-term prophylactic infusions beyond five years is not yet known. The hope is that gene therapies may provide freedom for patients and caregivers from the need for regular, ongoing infusions, which may impact their quality of life and required infusion interventions.…
For sickle cell disease, the only curative treatment available is a bone marrow transplant. It is usually considered only for those patients with severe disease complications, including repeat strokes and painful events. Other treatments only manage symptoms, lower the frequency of acute pain and reduce the risk of complications. Lovo-cel and exa-cel have been shown to sustain levels of healthy red blood cells and reduce the frequency or eliminate acute episodes of severe pain and organ damage.
In August of this year, ICER agreed in their final report on sickle cell disease gene therapies that current evidence is adequate to demonstrate a net health benefit for exa-cel and lovo-cel when compared to standard of care like hydroxyurea, chronic blood transfusions, pain medication and iron chelation therapy.
While the multimillion price tag for gene therapy cannot be ignored, the cost may be offset by potentially eliminating ongoing therapy that is not curative and has a significant impact on the patient’s quality of life. If the therapeutic activity of gene therapies can be maintained for years to come without causing serious adverse effects while demonstrating continued sustained efficacy and measurable clinical endpoints, the treatment paradigm for many hematologic disease states may likely be impacted.
AIS Health: How significant would approval of lifileucel be if it were to happen?
Szczotka: Lifileucel is an experimental treatment for advanced melanoma utilizing immune cells called tumor infiltrating lymphocyte (TIL) therapy. The therapy involves altering a patient’s own cells, which are extracted from a tumor and then re-engineered. Ultimately, rejuvenated cells are reinfused back into the body. Study data suggests that lifileucel delivered durable responses and a favorable safety profile in patients with advanced melanoma. If approved, lifileucel would be the first one-time cell therapy available to treat a solid tumor cancer.
This is significant because solid tumors account for approximately 90% of adult cancers. Solid tumors include cancers of the brain, ovary, breast, colon and other tissues. Many researchers believe that one quality solid tumors share is a reliance on cancer stem cells. These cancer stem cells are thought to divide to produce the bulk of the cells that make up the tumor. The hypothesis suggests that unlike most cells of a tumor, the cancer stem cells divide very slowly and are less likely to be destroyed by chemotherapies that kill the fast-growing tumor cells. The thought is that cancers might recur because chemotherapy kills the bulk of the tumor but leaves behind the cancer stem cells that can, over time, form a new tumor. The potential to alter the cancer stem cells in a single treatment, like lifileucel, could significantly improve cancer treatment for a range of different cancer types.
AIS Health: Coherus just disclosed that the FDA gave it a complete response letter (CRL) for Udenyca (pegfilgrastim-cbqv) Onbody due to “inspection findings at a third-party filler.” Do you expect those to be resolved quickly? How significant would approval of this agent be?
Szczotka: The Udenyca Onbody is a pegfilgrastim biosimilar with the same delivery method as Neulasta Onpro.…The CRL did not identify any issues with clinical efficacy or safety, trial design, labeling, drug substance manufacturing or device design and manufacturing. No additional data or trials have been requested by the FDA. Therefore, it is likely that inspection issues can be resolved in the short term compared to a CRL that requires additional clinical studies, data or is due to safety concerns.
The FDA has approved six Neulasta biosimilars, but all of them have been approved for use as a manual subcutaneous injection. Neulasta Onpro has over 50% of the pegfilgrastim market share. The device is prefilled with pegfilgrastim and attached to the abdomen or back of the arm of a person undergoing chemotherapy. Instead of having to return to the provider’s office for pegfilgrastim administration, the device automatically administers a dose of the drug on the day following chemotherapy.
The availability of the Udenyca Onbody system could impact a biosimilar’s uptake in a positive way, as it now offers a product that can compete with the dosage form that has been unique only to Neulasta Onpro. Despite the availability of numerous pegfilgrastim biosimilars, many patients and providers have continued to utilize the Onpro dosage form. Currently, the Udenyca prefilled syringe offers a 35% discount to the Neulasta prefilled syringe. Once approved, Udenyca Onbody will provide another desirable treatment option for chemotherapy patients, hopefully at a significantly discounted price.
AIS Health: What are payer takeaways from this report?
Szczotka: Specialty drugs continue to be the main category in the FDA’s pipeline for new approvals during third quarter 2023. Approvals for drugs utilized to treat devastating disease states such as Alzheimer’s, myasthenia gravis and ALS provide hope for an improved quality of life for patients and their caregivers.
However, they also have the potential to contribute to an increase in payer drug spend. Recent gene and cell therapy approvals, as well as the medications in the pipeline, offer the hope of a cure for previously uncurable disease states such as hemophilia and sickle cell disease. Existing treatments are very costly, some with rigid and demanding treatment schedules, that ultimately still allow the disease to progress. Payers will need to evaluate the benefits and risks of these therapies, including safety, durability and cost. In addition, the FDA plans to use the accelerated approval pathway more often with cell and gene therapies, which payers may want to consider as they look at coverage.
While more biosimilars continue to be approved, providing additional treatment options and lower costs, their impact is looming. Specifically, adalimumab formulary positioning, lower pricing strategies, additional products with higher strengths and interchangeability designations will likely make a more significant impact in the marketplace in 2024. The addition of biosimilars for new disease states and new delivery systems will help to continue the impact of biosimilars in the market with more treatment options and improved pricing.
Contact Szczotka via Caroline Chambers at email@example.com.
By Angela Maas