An estimated 7.5 million live with psoriasis in the United States alone. An autoimmune disease that surfaces on the skin as raised, red itchy patches, it starts inside the body. An estimated 79 million struggle with the genetic disease that can be triggered by environmental factors. Some uncontrolled studies articulate diet as a key consideration.
Apremilast (Otezla) is an oral medication for the treatment of certain types of psoriasis and psoriatic arthritis. It may also be used for other immune system related inflammatory diseases. Acting as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) it inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. The drug exploited a new mechanism of action as the first inhibitor of PDE4 that results in increased expression of both anti-inflammatory proteins and reduced expression of their pro-inflammatory counterparts.
Developed by American drug manufacturer Celgene, the drug was approved by the United States Food and Drug Administration (FDA) in 2014 for treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis. In Europe the drug is contraindicated during pregnancy because mice and monkeys receiving very high doses of the drug have been observed to suffer miscarriages and other pregnancy problems. The U.S. has made an exception “if the potential benefit justifies the potential risk to the fetus.” Common side effects are published by the drug sponsor Celgene.
The drug is approved in the European Union for moderate to severe plaque psoriasis. It can be used there for patients who have not responded to or cannot use other systematic (affecting whole body) treatments for psoriasis, such as ciclosporin, methotrexate or PUVA (psoralen ultraviolet A). PUVA is a type of treatment where the patient receives a medicine containing a compound called a ‘psoralen’ before being exposed to ultraviolet light. Active psoriatic arthritis (inflammation of the joints associated with psoriasis) is another example. Otezla may be used alone or combined with other DMARDS. The EU has questions however. It notes in A 2014 document titled “Summary of the risk management plan (RMP) for Otezla (apremilast)” Otezla is mostly used by a white population. The EU isn’t certain but doesn’t believe it is highly probable that it would generate different results in a non-white population. Otezla studies precluded those patients with moderate/severe kidney disorders, live disorders, children and pregnant or breastfeeding patients were not included in clinical trials. No information exists for this targeted patient group. There are a number of risks the EU considered including cancer. They noted in some situations “patients taking Otezla in studies have developed cancer and so this is considered a potential risk.” The EU notes however that many of the patients came to the study with preexisting risk patterns (e.g. family history, history of prior skin cancer, etc.). Moreover, “these events were diagnosed in the first six months of starting treatment with the medicine, and since cancers usually take some time to develop it is unlikely that the occurrence of the malignancies is connected with Otezla.”
We share this latter explanation with our readers that requested TrialSite News review any incidences of cancer. TrialSite News does have incoming requests to investigate this drug and others and their potential association with cancer.
Drug Brand Status A Slow Start
It was considered a “plain-Jane” drug by many—a dim view reported in a study in the Journal of the American Academy of Dermatology.” The study, funded by competitor AbbVie HUMIRA), included “an indirect comparison of two agents using results from existing studies for each drug.” Revealing no statistically significant difference “between Otezla and methotrexate in the Psoriasis Area Severity Index 75 (PASI 75) score a measure of the degree of skin plaque improvement in patients with 75 meaning 75% clearance.” The lead investigator, April Armstrong, MD from the University of Southern California, calculated that the annual cost for Otezla to achieve one additional PASI 75 responder would be $187,888.
The ICER Cost Analysis and Brand Boost
The Institute for Clinical and Economic Review (ICER) was a bearer of better news. After an analysis of Otezla relative to the increasing number of biologics for plaque psoriasis, (including Humira (adalimumab), Enbrel (etanercept), and Remicade (infliximab), plus new comers such as Stelara (ustekizumab) and Cosentyx (secukinumab)), it reported in November 2016 the wholesale acquisition cost of a month’s supply of Otezla was $2,586 and factoring in discounts, the total was $2,069. ICER determined that when the price point came down to around $2,069 range, Otezla was cost effective within an acceptable quality-adjusted life year (QALY) range of between $100,000 and $150,000. Compared to some of the other biologics, Otezla started to look like a bargain at $2,069 per month.
But Manage Care Magazine report authored by Thomas Reinke noted that many clinicians were looking at the drug in comparison to higher performing biologic agents. This report noted that “a new cohort of biologics with potentially better performance was in the offing and included Cosentyx and Tremfya (guselkimab).
In the United States the drug is available but dispensed on through a network of specialty pharmacies. The estimated wholesale price is $22,500 for a year of treatment. It is priced at approximately $3,556 per 60 tablets. In Austria the drug is available in all pharmacies and a year of treatment costs about 11,000 Euros as reported in “Warenverzeichnis” Österreichischer Apothekerverlag. January 2016.
Breaks A Billion for Blockbuster Status
By late last year it was reported sales of Otezla soared. Celgene reported on its third quarter results that sales of psoriasis drug Otezla surged by 40.3% to $432 million for Q3 2018—easily beating the average analyst estimate of $383.31 million according to Refinitiv
By Q4 2018 Celgene reported Otezla sales of $448 million, a 21% increase year-over-year. In the 4th Quarter 2018 U.S. sales were $360 million and international sales totaled $88 million which was a 19% and 29% increase respectively The industry sponsor reported increasing demand for Otezla. By the end of 2018 annual sales totals for Otezla broke $1.6 billion, an increase of 26% over the last year.
The Impending BMS Celgene Acquisition
U.S pharma Bristol-Myers Squibb has made a $74 billion offer to buy Celgene. Recently Endpoints reported that in an Securities and Exchange Commission Filing (SEC) that the Federal Trade Commission (FTC) requested additional information on “marketed and pipeline products for the treatment of psoriasis” while it conducted typical and normal antitrust reviews. Possibly the regulators were reviewing the overall psoriasis position int he markets. With an toward what kind of consolidation forces would emerge. After all, Otezla was Celgene’s “rising star. BMS has been developing a rival oral investigational TKY2 psoriasis drug known as BMS-986165. BMS was moving into the market with an eye on market entry. Are regulators delving into the impact of the BMS and Celgene acquisition on the anti-inflammatory market? Endpoints notes obviously BMS would seek to keep Otezla–$1.2 billion in sales in 2017 and $1.6 billion in 2018. Shareholders have approved the buyout and the transaction will close Q3 2019.
Otezla was approved for the first time by the FDA in 2014. In the U.S. it is now approved for psoriatic arthritis and moderate to severe plaque psoriasis. Although some reviews were critical it would appear that the ICER analysis triggered rapidly growing sales. According to ICER the drug price is justified at $2,069 per month. Sales reached $1.6 billion in 2018 only 4 years since its approval. This is astonishing growth. The EU has published a comprehensive risk guide for the drug.