FDA on a Roll, the Party Continues: Drug Approvals in 2018 (Part 2)

It was a golden year for the pharmaceutical industry in terms of FDA approvals. With 62 new molecular entity (NME) and biologic approvals in 2018, all records were broken to date (maximum being 59 in 1996).¹,² In the first part of this series, DRG observed that the FDA’s Center for Drug Evaluation and Research (CDER) had made, on average 32 approvals over the last ten years, with 46 approvals in 2017 and only 22 in 2016 (Figure 1). In H1 of 2018, 16 NMEs and 8 biologics license applications (BLAs) were approved by the FDA.³ With 42 NMEs and 20 biologics approved by CDER and the Center for Biologics Evaluation and Research (CBER), the FDA ended 2018 with flying colors before closing for Christmas (Tables 1 and 2). In total, 149 approvals have been made in all submission categories (type 1 to 10), including three BLA supplements.

It was no surprise that oncology topped the list with 18 approvals (Figure 1b) along with popularity of rare indications. Among the 62 approvals, 55% (34 NMEs and BLAs) were orphan designations; a tremendous increase from the past two years (39% for 2017 and 41% in 2016).^4,5 The FDA continues to offer expedited review benefits to drugs, helping patients to gain quick access to much needed therapies. Among the 59 NMEs approved by CDER in 2018, 43 (73%) were designated to have either one or more of the expedited review categories - fast track, breakthrough, accelerated approval, and priority review. In 2018, 50% of drug approvals had priority review status. Many companies received approvals for their molecules. Pfizer was the only company to get four approvals (and in a span of three months). All four oncology products will strengthen its portfolio. A few other companies, such as AstraZeneca, Shionogi, Eli Lilly, and Array BioPharma, received approvals for two products each.

According to DRG estimates, eight of these molecules are expected to cross the US $ 1 billion mark onto the list of block busters. Of these molecules, five are biologics. In 2018 we saw the approvals of some major blockbusters including Gilead’s Biktarvy (bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate), a combination of integrase strand transfer inhibitor and nucleoside reverse transcriptase inhibitor, Janssen’s Erleada (apalutamide), an androgen receptor inhibitor, Eli Lilly’s Olumiant (baricitinib), a JAK inhibitor, and Regeneron/Sanofi’s Libtayo (cemiplimab), a fully human PD-1 monoclonal antibody (MAb). In addition to oncology drugs Erleada and Libtayo, two migraine drugs, Amgen/Novartis’s Aimovig (erenumab) and Eli Lilly’s Emgality (galcanezumab), are forecast to be block busters in three to five years.

Biktarvy, a once-daily, single-tablet option, is expected to be one of the biggest launches of the year and growth drivers for the HIV market. It will strongly compete with ViiV’s Triumeq (dolutegravir/abacavir/lamivudine). The improved long-term renal and bone safety seen with tenofovir alafenamide fumarate and the absence of a booster make Biktarvy a safer alternative to its competitors.

Erleada, the first FDA-approved therapy for nonmetastatic castration-resistant prostate cancer (nmCRPC) is expected to strengthen J&J’s position in the prostate cancer market. The drug exhibits a strong efficacy benefit and has been added to the NCCN guidelines as a category 1 recommendation for treatment of nmCRPC, which will significantly influence treatment of this disease.

Olumiant, the second JAK inhibitor in the U.S. market, was approved approximately six years after Pfizer’s Xeljanz (tofacitinib) for moderate to severe rheumatoid arthritis. With a price that is about 60% of Humira and the wide use of JAK inhibitors in inflammatory diseases, Olumiant is expected to become a blockbuster.

Libtayo, a fully human MAb targeting the immune checkpoint receptor PD-1, was approved in September by the FDA for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or radiation. This drug is the first approved treatment for advanced CSCC, the second most popular form of skin cancer. Results from both the phase II EMPOWER-CSCC-1 clinical trial and a Phase I trial led to its getting priority review. Additionally, Libtayo is under development for various advanced malignancies, such as NSCLC, solid tumors, and hematological cancers, either alone or in combination.

Aimovig, an anti-CGRP MAb, is the first therapy to be developed for migraine prevention and is a promising option for patients who cannot find relief or tolerate the side effects of currently available therapies. Apart from having first-mover advantage, the drug also differentiates from others by targeting the CGRP receptor rather than the CGRP molecule and thus is forecast to be a block buster. Aimovig offers a clean side-effect profile free from any warnings, precautions, and contraindications and can be self-administered with SureClick® autoinjector. Both Amgen and Novartis have made plans to ease the burden on patients as the drug faces access and reimbursement issues in the United States.

Emgality is a humanized MAb and CGRP antagonist that in addition to being approved for migraine prophylaxis is in development for cluster headache. The drug is also well tolerated and has a clean side effect profile, with no warnings or contraindications on its label. Like Aimovig, Emgality faces payer restrictions but Eli Lilly is offering patient-assistance programs for this drug. It can also be self-administered by patients at home once a month.

The increasing number of approvals raises the question of whether deregulation, process improvement, or higher risk-taking by companies leads to faster approvals. The FDA is certainly taking measures to bring medicines as quickly as possible to patients. In 2018, 42 of the 59 novel drugs approved (71 %) got their first approval in the United States before receiving approval in any other country. FDA’s CDER is now working more closely with companies, especially during designing their clinical studies and building NDAs for submission. This helps the companies to get approvals in the first cycle (6 to 12 months) of the approval process itself. In 2018, 95% of the novel drugs got approval in the first cycle, giving quick access of new drugs to the patients.⁶

A large number of expedited reviews, orphan drug designations, and approvals of high-priced drugs for rare indications are some of the trends shaping the future of pharmaceutical industry. Factors such as advancements in diagnostic techniques, investment in research in genomics, proteomics, and mapping of the human genome, and conducting biomarker-enriched clinical trials are going to increase precision-based drug approvals in future. The FDA is expected to bring in new innovative initiatives focusing on efficient and well-informed approvals, in a timely manner to bring safe and effective therapies to patients.

Table 1. NMEs Approved in 2018¹

Table 2. BLAs Approved in 2018 by CDER and CBER^1,7

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References:

1. Drugs@FDA, https://www.accessdata.fda.gov/scripts/cder/daf/.
2. Mullard A, 2017 FDA drug approvals, Nature Reviews Drug Discovery, 19 Jan 2018.
3. FDA on a Roll: Drug Approvals in H1 2018, Decision Resources Group, Blog, 9 August 2018 https://decisionresourcesgroup.com/drg-blog/fda-roll-drug-approvals-h1-2018/.

4. Advancing health through innovation 2017 new drug therapy approvals, https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ReportsBudgets/UCM591976.pdf. Accessed on July 12, 2018.
5. 2016 Novel drugs summary, https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM536693.pdf. Accessed on July 12, 2018.
6. 2018: A Year of Innovation, Efficiency, and New Advances in Drug Therapy for the American Public, FDA Press Release, January 7, 2019.
7. 2018 Biological License Application Approvals, https://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/BiologicalApprovalsbyYear/ucm596371.htm. Accessed on January 5, 2019.

DRG Sources Used:

1. Biktarvy: Disease Landscape & Forecast, Human Immunodeficiency Virus, October 2018, Decision Resources Group.
2. Erleada: Disease Landscape & Forecast, Prostate Cancer, December 2018, Decision Resources Group.
3. Olumiant: Disease Landscape & Forecast, Rheumatoid Arthritis, October 2018, Decision Resources Group.
4. Libtayo: Real World Brand Tracker January 2016 to August 2018, December 2018, Decision Resources Group.
5. Aimovig, Emgality: Disease Landscape & Forecast, Migraine, November 2018, Decision Resources Group.

Garima Kaul, PhD, MPharm., is a senior director in the market assessment team at Decision Resources Group. She has 15 years’ experience in the field of pharmaceutical business analytics and market research involving market assessment, competitive intelligence, opportunity assessment, social media analysis, and forecasting. She has supported many open innovation initiatives across the globe. Dr. Kaul has authored 22 publications in peer-reviewed international journals, 2 patent applications, and 1 book chapter. In addition, she has acted as a reviewer for many journals.