Specialty Pipeline Highlights

Approvals for new drugs to treat orphan conditions and asthma are expected.

The FDA approved several new specialty medications in the first quarter of 2015, including 3 oral cancer medications.

On February 3, Pfizer’s Ibrance (palbociclib) was approved as first-line therapy with letrozole for the treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Ibrance works by inhibiting cyclin-dependent kinases 4 and 6, thereby blocking the growth of cancer cells.

Eisai received approval on February 13 for Lenvima (lenvatinib), a receptor tyrosine kinase inhibitor (TKI) to treat patients with advanced radioiodine-refractory differentiated thyroid cancer. On February 23, Novartis’ Farydak (panobinostat) was approved for the third-line treatment of multiple myeloma in combination with Velcade (bortezomib; Takeda) and dexamethasone.

On March 6, Zarxio (filgrastim-sndz; Sandoz) was the first biosimilar to receive FDA approval. It is a noninterchangeable biosimilar to Amgen’s Neupogen, a colony-stimulating factor that increases the production and release of white blood cells from the bone marrow.

Sandoz launched Zarxio on September 3. The second quarter of 2015 was unusually quiet with only 1 specialty drug approval.

Emergent BioSolutions’ Ixinity (coagulation factor IX [recombinant]) was approved April 30 for treatment of patients with hemophilia B. The third quarter started off with the approval of Orkambi (lumacaftor/ivacaftor; Vertex), an oral combination tablet that treats the underlying disease in patients with cystic fibrosis (CF) who are 12 years and older who are homozygous for the F508del mutation in the CF transmembrane conductance regulator gene.

Approximately 8500 patients in the United States are candidates for treatment with Orkambi. The wholesale acquisition cost of Orkambi is $259,000 per year, which is about 16% less than Kalydeco (ivacaftor; Vertex).

Kalydeco, which was approved in 2012, treats the underlying disease in approximately 1950 patients in the United States with certain CF gating mutations. Several additional specialty medications were approved in the third quarter, including new drugs to treat high cholesterol and hepatitis C.

Sanofi and Regeneron’s Praluent (alirocumab) and Amgen’s Repatha (evolocumab) are proprotein convertase subtilisin kexin type 9 inhibitors approved for the treatment of high cholesterol among patients with heterozygous familial hypercholesterolemia or patients with clinical atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein “bad” cholesterol. Repatha was approved to treat patients with homozygous familial hypercholesterolemia.

Both drugs, which are administered by subcutaneous injection, are used along with diet and maximally tolerated HMG-CoA reductase inhibitor (statin) therapy. They cost approximately $14,000 per year.

Two new new oral drugs to treat hepatitis C were approved July 24. AbbVie’s Technivie (ombitasvir, paritaprevir, and ritonavir) was approved for use in combination with ribavirin for the treatment of hepatitis C virus (HCV) genotype 4 infection in patients without cirrhosis (scarring and poor liver function).

Bristol-Myers Squibb’s Daklinza (daclatasvir) was approved for the treatment of patients with HCV genotype 3 infection in combination with Sovaldi (sofosbuvir; Gilead). In the remainder of 2015, watch for several new drugs to treat orphan conditions and a new specialty drug to treat asthma.

The approval of additional biosimilars is also possible later this year. More information about selected specialty pipeline medications can be found below.

Non-Small Cell Lung Cancer

AstraZeneca’s osimertinib and Clovis Oncology’s rociletinib are third-generation epidermal growth factor (EGFR) inhibitors that are pending approval for patients who have the EGFR T790M mutation-positive non-small cell lung cancer whose disease has progressed following treatment with EGFR-TKIs such as Tarceva (erlotinib; Genentech/Astellas) or Gilotrif (afatinib; Boehringer Ingelheim). There are about 190,000 new cases of NSCLC diagnosed each year in the United States.

EGFR-activating mutations occur in 10% to 35% of patients and currently available EGFR-TKIs are therapeutic options for these patients. However, approximately 60% of patients eventually develop acquired resistance from the T790M “gatekeeper” mutation.

Osimertinib and rociletinib have been granted breakthrough therapy designations for this population due to the unmet need. Osimertinib and rociletinib are oral medications taken once daily and twice daily, respectively.

Osimertinib is associated with rash and diarrhea while rociletinib can cause hyperglycemia. Both Osimertinib and rociletinib are expected to be approved by early 2016.

{Click image to enlarge}

Duchenne Muscular Dystrophy

BioMarin Pharmaceutical’s drisapersen and Sarepta Therapeutics’ eteplirsen are medications that are pending approval to treat the underlying disease in certain patients with Duchenne muscular dystrophy (DMD). DMD is a debilitating childhood neuromuscular disease caused by mutations in the dystrophin gene that result in the absence or defect of the dystrophin protein.

Patients with DMD experience progressive loss of muscle function; the disease is typically fatal in early adulthood due to respiratory and cardiac failure. There currently are no drugs approved to treat the underlying disease in patients with DMD.

Drisapersen and eteplirsen work by inducing exon 51 skipping of the dystrophin gene. This enables the production of a functional dystrophin protein.

Approximately 13% of patients with DMD have an exon 51 gene mutation; therefore, about 2000 boys in the United States will be candidates for treatment with drisapersen or eteplirsen.

Drisapersen is administered as a weekly subcutaneous injection; approval is expected by December 27, 2015. Eteplirsen is administered as a weekly intravenous infusion; approval is expected by February 26, 2016.

Hepatitis C

Merck’s grazoprevir/elbasvir is a fixed-dose combination tablet that is expected to be approved by January 28, 2016, for the treatment of HCV genotypes 1, 4, and 6. Grazoprevir is a second-generation protease inhibitor and elbasvir is an NS5A inhibitor.

The recommended treatment regimen is 1 tablet, once daily for 12 weeks. Grazoprevir/elbasvir has been granted breakthrough therapy designation for the treatment of patients with HCV genotype 4 infection and for the treatment of HCV genotype 1 infection in patients with end stage renal disease on hemodialysis. SPT

About the Author

Aimee Tharaldson, PharmD, is a senior clinical consultant in the Emerging Therapeutics Department at Express Scripts. She is responsible for monitoring and analyzing the specialty pharmaceutical pipeline. The Emerging Therapeutics Department produces several proprietary reports on the pipeline for use by Express Scripts’ employees and clients. It is also responsible for the safety program that alerts patients, physicians, and clients to important information regarding serious drug safety alerts and market withdrawals. She contributes to Express Scripts’ Drug Trend Report and plays a key role in developing and maintaining Express Scripts’ specialty drug list. She received her doctor of pharmacy degree from the University of Minnesota, College of Pharmacy, and completed a pharmacy practice residency at the Minneapolis VA Medical Center.