Rare Diseases/Orphan Drugs

Feb. 3: The FDA expanded the patient population for Takeda’s Takhzyro (lanadelumab-flyo) to include the prevention of hereditary angioedema attacks in people at least 2 years old. The agency initially approved the plasma kallikrein inhibitor on Aug. 3, 2018. Dosing of the subcutaneous injectable in people at least 12 years old is 300 mg every two weeks. In people at least 6 and less than 12, dosing is 150 mg every two weeks, and for people 2 years old and younger than 6, dosing is 150 mg every four weeks. Drugs.com lists the price of one single-dose 300 mg/2 mL subcutaneous solution as more than $26,165.

Feb. 8: The FDA granted another indication to Regeneron Pharmaceuticals, Inc.’s Eylea (aflibercept) for the treatment of retinopathy of prematurity in preterm infants. The agency first approved the drug on Nov. 18, 2011. Dosing of the vascular endothelial growth factor (VEGF) inhibitor for the newest indication is 0.4 mg via intravitreal injection; treatment may be given bilaterally on the same day. Injections may be repeated with an interval of at least 10 days. Drugs.com lists the price of a 40 mg/ml intravitreal solution as more than $1,957.

Jan. 19: The FDA expanded the label of BeiGene, Ltd.’s Brukinsa (zanubrutinib) to include the treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma. The agency initially approved the Bruton’s tyrosine kinase (BTK) inhibitor on Nov. 14, 2019. The agency granted the application orphan drug designation, and its review used the Assessment Aid. The recommended dose of the capsule is 160 mg twice daily or 320 mg once daily. Drugs.com lists the price of 120 80 mg capsules as more than $15,264.

Jan. 19: The FDA granted accelerated approval to Seagen Inc.’s Tukysa (tucatinib) in combination with trastuzumab for the treatment of adults with RAS wild-type, human epidermal growth factor receptor 2 (HER2)-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. The company says the tyrosine kinase inhibitor is the first FDA-approved treatment in HER2-positive metastatic colorectal cancer. The agency first approved the drug on April 17, 2020. The newest indication had priority review and breakthrough therapy designation. Dosing for the tablet is 300 mg twice daily. Drugs.com lists the price of 60 150 mg tablets as more than $12,389.

While the launches of biosimilars of AbbVie Inc.’s best-selling drug Humira (adalimumab) are arguably the top entrants expected on the U.S. marketplace in 2023, numerous other specialty agents are expected to join them. AIS Health, a division of MMIT, spoke with multiple industry experts on what they’re keeping an eye on in the late-stage pipeline.

AIS Health: Are there any big specialty drugs expected to see patent expiration — and potentially generic or biosimilar competition — in 2023?

Nicole Kjesbo, Pharm.D., director of clinical program development for Prime Therapeutics LLC: Generics are expected to launch in 2023 for [AstraZeneca’s] Iressa (gefitinib), [Jazz Pharmaceuticals plc’s] Xyrem (sodium oxybate), [Novartis Pharmaceuticals Corp.’s] Sandostatin LAR (octreotide acetate) and Thalomid (thalidomide) [from Bristol Myers Squibb unit Celgene Corp.]. Stelara [(ustekinumab) from Johnson & Johnson unit Janssen Biotech, Inc.] (IV/SC) and IV Actemra [[(tocilizumab) from Genentech USA, Inc., a member of the Roche Group] lose their exclusivity in 2023.

While the FDA may not have approved the most drugs in a year in 2022, it still gave the green light to a number of agents, many of them specialty medications, as well as granted additional indications to existing therapies. The FDA’s Center for Drug Evaluation and Research (CDER) approved 39 new molecular entities in 2022, and the Center for Biologics Evaluation and Research (CBER) approved 12 biologic license applications, including four new gene therapies in the second half of the year. AIS Health, a division of MMIT, asked some industry sources what the most notable 2022 FDA approvals were and why they were so important.

The FDA recently approved the fifth gene therapy to gain FDA approval, with three of those decisions coming in the second half of this year. While payer respondents to a Zitter Insights survey have expressed interest in the drug, its price may prove to be an obstacle to coverage.

On Nov. 22, the FDA approved uniQure N.V.’s Hemgenix (etranacogene dezaparvovec-drlb) for the treatment of people at least 18 years old with hemophilia B who currently use factor IX prophylaxis therapy or have current or historical life-threatening hemorrhage or have repeated serious spontaneous bleeding episodes. CSL Behring LLC, a CSL business, will market the gene therapy. The agency gave the first-in-class adeno-associated virus A5-based gene therapy — which previously was known as EtranaDez — priority review and orphan and breakthrough therapy designations.

As researchers gain growing insight into the mechanics of what makes diseases tick, more and more genetic tests are coming onto the market to help make sure the right patient gets the right drug at the right time. While these diagnostics can help inform diagnosis and treatment for patients, the sheer volume of these tests may be overwhelming payers in their coverage decisions. Stakeholders should work together to help establish the clinical utility that payers need to make coverage decisions on these diagnostics, industry experts say.

Daryl Pritchard, Ph.D., senior vice president of science policy at the Personalized Medicine Coalition (PMC), describes the landscape of coverage for genetic testing as “uneven. Payers are increasingly considering coverage and reimbursement of genetic testing products and services.” However, he tells AIS Health, a division of MMIT, “there remain significant challenges in establishing coverage policies and payment rates for diagnostic tests that reflect the value of their care. As a result, many newer novel diagnostics are under-reimbursed or not covered at all. Such practices ultimately restrict patient access to some needed tests and to optimal care. Coverage and reimbursement policies vary widely among different payers, and decision-making processes are often inconsistent and not transparent.”

Two recently published studies by Prime Therapeutics LLC shine a light on specialty drug costs. In the first, researchers found that a newer agent for cystic fibrosis is effective, but it is so costly that its related savings in health care services avoided do not offset its cost. The second study showed that a focused communication effort for a transition to a preferred infliximab biosimilar, among other strategies, has resulted in millions of dollars in savings in only the first three months after implementation of the strategy.

Posters on the studies were presented at the Academy of Managed Care Pharmacy (AMCP) Nexus meeting.

As researchers gain growing insight into the mechanics of what makes diseases tick, more and more genetic tests are coming onto the market to help make sure the right patient gets the right drug at the right time. While these diagnostics can help inform diagnosis and treatment for patients, the sheer volume of these tests may be overwhelming payers in their coverage decisions. Stakeholders should work together to help establish the clinical utility that payers need to make coverage decisions on these diagnostics, industry experts say.

Daryl Pritchard, Ph.D., senior vice president of science policy at the Personalized Medicine Coalition (PMC), describes the landscape of coverage for genetic testing as “uneven. Payers are increasingly considering coverage and reimbursement of genetic testing products and services.” However, he tells AIS Health, a division of MMIT, “there remain significant challenges in establishing coverage policies and payment rates for diagnostic tests that reflect the value of their care. As a result, many newer novel diagnostics are under-reimbursed or not covered at all. Such practices ultimately restrict patient access to some needed tests and to optimal care. Coverage and reimbursement policies vary widely among different payers, and decision-making processes are often inconsistent and not transparent.”

Sept. 9: The FDA approved Bristol Myers Squibb’s Sotyktu (deucravacitinib) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The agent is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor. The recommended dosage of the tablet is 6 mg once daily. The list price for a 30-day supply is $6,164.

Sept. 9: The FDA approved Spectrum Pharmaceuticals, Inc.’s Rolvedon (eflapegrastim-xnst) to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia. The manufacturer says it is the first novel long-acting granulocyte colony-stimulating factor (G-CSF) approved in more than 20 years. The recommended dose is 13.2 mg administered subcutaneously once per chemotherapy cycle. The company says it expects the product to be available in fourth-quarter 2022.

The manufacturers of many drugs granted accelerated approval by the FDA do not complete timely confirmatory trials of the drugs’ efficacy, according to a recent study published in the journal Health Affairs — meaning that the pricing for many accelerated approval drugs has nothing to do with their clinical efficacy. The study’s author tells AIS Health, a division of MMIT, that “the market doesn’t work very well” for drugs that have received accelerated approval, and “what it leads us to is overpaying at the beginning and underpaying, potentially, later.”

After a drug is granted accelerated approval, the FDA mandates that the drug be evaluated using confirmatory clinical trials. The accelerated approval designation is given to new, unproven drugs that could potentially meet a dire need for a new or more effective therapy to treat a terminal disease. The intention behind the confirmatory trial system is to make sure that the drug actually does what its developer says it will.