Drug Update: January 2017 Issue 2

Specialty Drug News

New Review Date for Rheumatoid Arthritis Drug

Last week the manufacturer of baricitinib, a new therapy for rheumatoid arthritis, announced the U.S. Food & Drug Administration (FDA) has extended the review period for the investigational agent by 3 months. A decision regarding approval of baricitinib was previously expected by January 19, 2017. Eli Lilly and Incyte Corporation are developing the drug, and they have stated the extended review date allows for time to review additional data recently submitted by request of FDA.

Baricitinib is a once-daily oral medication being reviewed for the treatment of moderate to severe rheumatoid arthritis (RA). The new drug acts as a Janus Associated Kinase (JAK) inhibitor and would compete directly with the other oral JAK inhibitor indicated for moderate to severe RA, Xeljanz®/Xeljanz XR® (tofacitinib/tofacitinib XR). In addition, phase II trials are underway evaluating baricitinib for atopic dermatitis and systemic lupus erythematosus. A phase III trial evaluating its use in patients with psoriatic arthritis is expected to begin this year.

The safety and efficacy of baricitinib for patients with moderate to severe RA has been evaluated in four phase III clinical studies. In these clinical trials, baricitinib has been compared to methotrexate (RA-BEGIN trial), Humira® (adaliumumab; RA-BEAM trial), and placebo (RA-BUILD trial). A variety of patients have been evaluated in these clinical trials including those who are methotrexate-naïve as well as those with an inadequate response to methotrexate, conventional disease-modifying anti-rheumatic drugs (DMARDs), or to biologic DMARDS such as tumor necrosis factor (TNF) inhibitors. A long-term extension study is also underway.

NPS plans to provide ongoing communication regarding the FDA review of baricitinib. For additional information, please view the manufacturer’s press release on the extended review date.

New Review Date for Ocrelizumab

The FDA was expected to make a decision regarding approval of the much-anticipated new multiple sclerosis drug, Ocrevus® (ocrelizumab) by the end of December 2016, however the agency has extended the review date for the medication to March 28, 2017. The manufacturer of Ocrevus has stated the change in review date was based on submission of additional data regarding the manufacturing process, and was not related to any safety or efficacy concerns.

Ocrelizumab is a humanized monoclonal antibody that received Breakthrough Therapy designation by the FDA for the treatment of primary progressive multiple sclerosis (PPMS). Currently there are no approved treatments for PPMS. Ocrelizumab is also being reviewed by the FDA for the treatment of relapsing multiple sclerosis (RMS). Ocrelizumab works by targeting CD20-positive B-cells which are thought to contribute to nerve cell damage that leads to disability in multiple sclerosis.

The Biologics License Application (BLA) currently being reviewed includes data from three phase III studies: OPERA I, OPERA II, and ORATORIO. In OPERA I and II, ocrelizumab demonstrated superior efficacy to Rebif® (interferon beta-1a) in reducing the annualized relapse rate and disability progression in patients with RMS. In ORATORIO, ocrelizumab demonstrated significant reductions in disability progression compared to placebo in PPMS patients. The most common side effects observed with ocrelizumab were infusion-related reactions and infections. Ocrelizumab is administered by intravenous infusion as a 600 mg dose every 6 months.

For additional information on the extended review date for ocrelizumab, please view the manufacturer’s press release.

FDA Review News

Complete Response Letter Issued for Solithromycin

At the end of December, the manufacturer of solithromycin, Cempra, announced they had received a Complete Response Letter (CRL) from the FDA in regards to their New Drug Applications for oral and intravenous solithromycin. The antibiotic was being reviewed for the treatment of adults with community-acquired bacterial pneumonia. The CRL states the FDA cannot approve the applications in their current forms and that additional clinical safety information as well as satisfactory resolution of manufacturing deficiencies are necessary before approval.

The FDA stated specifically the risk of liver toxicity had not been adequately characterized, and therefore a comparative study in 9,000 patients to evaluate the risk was recommended. They also stated product labeling will need to include information regarding the risk for liver damage and that use should be limited to patients without other therapeutic options. In addition, a detailed plan for post-marketing safety analyses would also be needed. For more information, please view the manufacturer’s press release.

Biosimilar Update

FDA Issues Final Guidance on Non-Proprietary Naming of Biologics

In mid-January, the FDA released the final guidance on the “Nonproprietary Naming of Biological Products.” This much-anticipated guidance describes the naming convention that will be employed to distinguish originator biological products and biosimilar products. Biological products previously and newly approved will have a nonproprietary name that includes a designated FDA four lowercase letter suffix. The suffix will be devoid of meaning and will be attached to the product’s core name with a hyphen.

The naming convention will be used to distinguish between biological products and is designed to ensure safety and enhance patient / prescriber confidence. The FDA is still in the process of determining the appropriate suffix convention for interchangeable products. To view the guidance on the naming convention in its entirety, please visit the FDA website.

FDA Issues Draft Guidance on Interchangeability

Earlier this week, the FDA issued draft guidance on the “Considerations in Demonstrating Interchangeability with a Reference Product.” The guidance is intended to assist manufacturers in demonstrating that a proposed biological product is interchangeable with a reference product. The draft guidance includes information on the type and amount of data required to demonstrate interchangeability as well as considerations on the design of studies to demonstrate interchangeability.

Interchangeable biologic products are biosimilar products that have met additional criteria to be deemed interchangeable with the reference product. As a result, interchangeable biologic products can be substituted for the reference product by a pharmacist without intervention of the prescribing healthcare provider. Biosimilar products deemed to be interchangeable are expected to produce the same clinical outcomes as the reference product in any given patient, and the risk of safety issues or decreased efficacy by switching between the interchangeable product and the reference product is no greater than the risk of continuing use with the reference product.

NPS plans to provide ongoing communication regarding the finalized interchangeability guidance as well as on biologic products deemed interchangeable. For additional information on biosimilars, please visit the FDA’s Information on Biosimilars webpage. For a summary of the draft guidance, please view the FDA’s From Our Perspective article, and to review the draft guidance on interchangeability in its entirety, please visit the FDA website.



  1. BRIEF-U.S. FDA extends review period for baricitinib, an investigational rheumatoid arthritis treatment. Reuters. http://www.reuters.com/article/idUSFWN1F30T6. Updated January 13, 2017. Accessed January 16, 2017.
  2. Major Amendment to baricitinib NDA sets back FDA review three months. The Pharma Letter. http://www.thepharmaletter.com/article/major-amendment-to-baricitinib-nda-sets-back-fda-review-three-months. Updated January 16, 2017. Accessed January 16, 2017.
  3. FDA extends review period for baricitinib, an investigational rheumatoid arthritis treatment. Lilly Press Release. https://investor.lilly.com/releasedetail.cfm?ReleaseID=1007957. Updated January 13, 2017. Accessed January 16, 2017.
  4. Lilly and Incyte announce submission of New Drug Application to FDA for oral once-daily baricitinib for treatment of moderate-to-severe rheumatoid arthritis. Lilly Press Release Archives. http://lilly.mediaroom.com/index.php?s=9042&item=137509. Updated January 19, 2016. Accessed January 13, 2017.
  5. Baricitinib demonstrates early response compared to placebo and significant improvement compared to adalimumab in patient-reported outcomes. Lilly Press Release. https://investor.lilly.com/releasedetail.cfm?ReleaseID=999230. Updated November 14, 2016. Accessed January 13, 2017.
  6. Brauser D. PDUFA review date for ocrelizumab for multiple sclerosis extended until March. Medscape Medical News. http://www.medscape.com/viewarticle/873583. Updated December 21, 2016. Accessed January 13, 2017.
  7. Cempra receives complete response letter from FDA for solithromycin NDAs. Cempra News Release. http://investor.cempra.com/releasedetail.cfm?ReleaseID=1005708. Updated December 29, 2016. Accessed January 13, 2017.
  8. Brennan Z. Non-proprietary naming of biologics and biosimilars: FDA finalizes guidance. Regulatory Affairs and Professionals Society. http://www.raps.org/Regulatory-Focus/News/2017/01/12/26572/Non-Proprietary-Naming-of-Biologics-and-Biosimilars-FDA-Finalizes-Guidance/. Updated January 12, 2017. Accessed January 13, 2017.
  9. Stanton D. ‘Meaningless suffixes’ slammed by industry in FDA naming guidance. BioPharma Reporter.com. http://www.biopharma-reporter.com/Markets-Regulations/Pfizer-and-industry-hit-out-at-US-FDA-s-naming-guidance. Updated January 13, 2017. Accessed January 13, 2017.
  10. From our perspective: Interchangeable biological products. U.S. Food & Drug Administration. http://www.fda.gov/Drugs/NewsEvents/ucm536528.htm. Updated January 17, 2017. Accessed January 17, 2017.
  11. Considerations in demonstrating interchangeability with a reference product; draft guidance for industry. U.S. Food & Drug Administration. https://s3.amazonaws.com/public-inspection.federalregister.gov/2017-01042.pdf. Updated January 12, 2017. Accessed January 17, 2017.

Drug Update: January 2017 Issue 1

Industry News

21st Century Cures Act Signed into Law

In mid-December, Congress passed and the President signed into law the 21st Century Cures Act. The nearly 1,000 page legislation provides funding for a variety of initiatives including efforts to aid in the fight against the opioid epidemic with $1 billion in grants over 2 years being given to states for preventing and treating drug abuse. Congress is tasked with the responsibility of appropriating the opioid epidemic funding to the states. Other provisions and funding include a streamlined approval process for drugs and medical devices by the Food and Drug Administration (FDA) as well as $500 million in funding for the FDA. Read more