2015 Report Card: How The Pharmaceutical Industry Fared
An FDA Record: 45 Novel Drugs Approved in 2015
2015 - It was a very good year. In fact, year-after-year, the FDA is approving more "novel" drugs or biologics than the year before. A novel drug is an innovative product that serves a previously unmet medical need or advances patient care and public health.
This is obviously good for patients, healthcare providers, and the pharmaceutical industry, too. During 2015 close to 100 new drugs were FDA-approved with 45 novel drugs given the go-ahead. These novel, and sometimes disputed, new drugs included treatments for patients with dangerously high cholesterol, a first-time biosimilar, a life-saving heart failure drug, and a controversial agent to boost women’s libido. Here's a review to see which ones might be hits - or misses - as we move into 2016.
16 Novel Products Are First-In-Class
Remarkably, 36% of the novel drugs or biologics approved in 2015 were 'First-in-Class', that is, the first medication available for that new drug class. These innovator products, and their uses, include:
- Addyi - hypoactive sexual desire disorder
- Bridion - reverses neuromuscular blockade
- Corlanor - heart failure
- Cosentyx - plaque psoriasis
- Darzalex - multiple myeloma
- Empliciti - multiple myeloma
- Entresto - heart failure
- Ibrance - advanced breast cancer
- Kanuma - lysosomal acid lipase deficiency
- Nucala - asthma maintenance adjunct
- Orkambi - cystic fibrosis
- Praluent - high cholesterol
- Praxbind - anticoagulant reversal agent
- Strensiq - hypophosphatasia
- Unituxin - pediatric neuroblastoma
- Xuriden - orotic aciduria
PCSK9 Inhibitors: A New Class of Cholesterol Busters
One of the important new drug classes that gained approval in 2015 was the potent cholesterol-reducing agents known as PCSK9 Inhibitors.
These drugs have been shown to drastically lower cholesterol and also work in patients with genetic and rare forms of high cholesterol that are difficult to treat. Analysts predict this class to gain blockbuster status, but they have a few drawback: they are not used as first-line agents, they are injectable, and they are pricey at roughly $14,000 per year.
Praluent: The First PCSK9 Inhibitor Approved
The first PCSK9 inhibitor out of the gate in the summer of 2015 was Sanofi and Regeneron’s Praluent (alirocumab). Praluent, given by subcutaneous injection once every 2 weeks, is specifically approved as an adjunct to diet and maximally tolerated statin therapy for adults with:
- Heterozygous familial hypercholesterolemia (HeFH)
- Clinical atherosclerotic heart disease who require further LDL lowering
The Second PCSK9 Inhibitor: Repatha
Amgen’s Repatha (evolocumab), the second PCSK9 inhibitor, was also approved in the summer of 2015. Repatha subcutaneous injection is indicated as an adjunct to diet and maximally tolerated statin therapy for:
- Heterozygous familial hypercholesterolemia (HeFH)
- Clinically significant heart disease that requires additional LDL-C lowering
- Adjunctive therapy in homozygous familial hypercholesterolemia (HoFH) when additional LDL-C lowering is needed.
Zarxio: First FDA-Approved Biosimilar Product
Although not listed as a 'novel' approval by the FDA, in 2015 progress was finally made in the approval of a U.S. biosimilar.
March was a history-making month when FDA approved Sandoz’s Zarxio (filgrastim-sndz), the first U.S. approved biosimilar. Zarxio, the biosimilar for Amgen’s filgrastim (Neupogen), is a recombinant granulocyte colony-stimulating factor used to boost white blood cells after cancer treatments. However, according to the FDA Purple Book, these two agents are not interchangeable by a pharmacist unless approved by the prescriber.
More Biosimilars in the Pipeline?
Biological products are generally derived from a living organism, including humans, animals, microorganisms or yeast. According to the RAND Corporation, biosimilars could save the U.S. health system close to $44 billion in the next ten years.
Addyi Clears FDA For Low Female Libido
Addyi (flibanserin) by Sprout Pharmaceuticals was FDA-approved in August 2015 for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.
Addyi, a multifunctional serotonin agonist antagonist (MSAA), is the first approved medication for HSDD. However, controversy swirled around marketing “disease awareness” tactics for Addyi, as well as concern about effectiveness of the drug in women and serious side effects.
What About Addyi Sales?
Unlike 'take-as-you need-it' Viagra for men, Addyi for women is taken every night as a 100-milligram bedtime dose and costs roughly $800 per month.
So far, sales of Addyi have been less than stellar. While Addyi showed modest benefit in clinical trials, it’s side effects, including fainting with alcohol use, prompted many labeling restrictions: a Boxed Warning, a REMS plan, required certification for providers and pharmacies, and a Patient-Provider Agreement Form.
Certification for doctors and pharmacists, worrisome side effects, and its high cost seem to be roadblocks.
An Anticoagulant Bleeding Reversal Agent
Praxbind (idarucizumab) approval in 2015 addressed a serious drawback to the newer anticoagulant Pradaxa (dabigatran); that there was no reversal agent for bleeding. This problem was remedied in October with the approval of Praxbind.
Praxbind is an intravenous injection that binds to Pradaxa to neutralize its effect and control bleeding.
Praxbind: It's Clinical Effect
In a study of 123 patients taking the direct thrombin inhibitor Pradaxa, patients were evaluated who received Praxbind due to uncontrolled bleeding or the need for emergency surgery. The anticoagulant effect of Pradaxa was fully reversed in 89 percent of patients within four hours. Common side effects include headache, low potassium (hypokalemia), confusion, constipation, fever and pneumonia.
Cancer Targets Continue in 2015
Novel drugs and biologics for various types of cancer continue to make strong headways with FDA approvals. In fact, 14 new cancer treatments were given the go-ahead in 2015. New approvals covered multiple areas:
- Multiple myeloma (a type of bone marrow cancer) - Darzalex, Empliciti, Farydak, Ninlaro
- Locally advanced basal cell carcinoma (a type of skin cancer) - Odomzo
- Advanced, metastatic breast cancer - Ibrance
- Soft tissues sarcomas - Yondelis
- Colorectal cancer - Lonsurf
- Pediatric neuroblastoma - Unituxin
- Thyroid cancer - Lenvima
- Lung cancer - Alecensa, Tagrisso
- Metastatic melanoma - Cotellic
Entresto Approved for Heart Failure Six Weeks Early
A drug product receiving FDA approval six weeks early can mean early life-saving treatments and millions more in dollars for its sponsor. In 2015, analysts said Entresto could peak at $6 to $8 billion per year. Then, in July, the U.S. Food and Drug Administration (FDA) approved Novartis’ Entresto, a twice-daily oral Angiotensin Receptor Neprilysin Inhibitor (ARNI) indicated to reduce the risk of death and hospitalization in patients with chronic heart failure.
Entresto contains a combination of sacubitril, a first-in-class neprilysin inhibitor, and valsartan, an angiotensin II antagonist already FDA approved as Diovan.
In the PARADIGM-HF Phase III study, Entresto was superior to ACE inhibitor enalapril. Entresto reduced the risk of death from cardiovascular causes and heart failure hospitalization by 20% and 21%, respectively, and reduced the risk of all-cause mortality by 16%.
In a December 2015 study published in the New England Journal of Medicine, researchers projected that patients who took Entresto would live 1.5 to 2 years longer than those who took enalapril (Vasotec), the current standard of care for patients with heart failure. However, enalapril is a well-known agent in clinical practice and an affordable generic. Concerns exist about the high price of Entresto at roughly $4,600 per year.
More Industry Outcomes: 21 New Orphan Drugs
Rare or “orphan” diseases affect 200,000 or fewer Americans. Accessing a drug for a rare disease can be a difficult task for clinicians and patients. Manufacturers often lack financial incentives to develop these orphan drugs, and many conditions remain without treatments. However, FDA does encourage and support development of these agents and growing numbers are approved each year. Noteworthy examples of orphan drugs approved in 2015 include:
Expediting Innovation to Market
The FDA uses four tracks to expedite approvals for much needed, innovative drugs: Fast Track, Breakthrough, Priority Review, and Accelerated Approval. Overall, 27 unique drugs received some type of expedited approval in 2015; many received multiple types of expedited approval. In addition, many of these drugs were orphan drugs for rare diseases where the need is greatest.
Quicker transit through the development, clinical trial, and approval process is a win-win for everyone: regulatory authorities, patients and families, and the pharmaceutical industry.
Top Drugs? Opinions Vary Widely
With so many new and novel approvals, it’s next to impossible to pick out those that are truly “tops.” But the latest drugs are varied and cutting-edge, so we had to pick a few.
What may be a top drug for one person — for example, an agent to extend survival from lung cancer — may not be a top drug to another patient who suffers from plaque psoriasis. How can a new treatment that treats advanced multiple myeloma be “better” than an approval for metastatic breast cancer. The bottom line is – they aren’t. Each novel drug from 2015 offers unique attributes and important health benefits.
Finished: 2015 Report Card: How The Pharmaceutical Industry Fared
- US Food and Drug Administration (FDA). Center of Drug Evaluation and research. Novel Drugs 2015. Summary. January 2016. Accessed January 17, 2015 at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM481709.pdf