ICER 2020 Priorities Include Drugs For Ulcerative Colitis, NASH And Gene Therapies

The Institute for Clinical and Economic Review has a full agenda planned for 2020, starting with potential new oral drugs for migraine.

The Institute for Clinical and Economic Review expects to initiate cost-effectiveness analyses for drugs in ulcerative colitis, non-alcoholic steatohepatitis (NASH) and blood disorders – but it could also change or add to the drugs it reviews.

ICER unveiled its proposed list of topics for review in 2020 on 9 July, though the list is preliminary and could change. ICER's agenda generally represents an opportunity to take stock of the year ahead, highlighting new drugs that are expected to launch and dynamic therapeutic areas that will be undergoing change.

The 2020 list calls out 18 drugs specifically that could be reviewed by ICER, on top of a previously announced review of three potential new drugs for acute migraine. ICER has already released the draft scoping documents ahead of a January 2020 public meeting for that review, which will include two oral CGRP receptor antagonists,
Biohaven Pharmaceutical Holding Co. Ltd.'s rimegepant and Allergan PLC's ubrogepant, as well as Eli Lilly & Co.'s 5-HT1f agonist lasmiditan.

The 2020 agenda includes one class review for drugs to treat ulcerative colitis. ICER has been steadily conducting class reviews for various inflammatory conditions. The value assessment group is currently conducting a class update for rheumatoid arthritis drugs and did a class review for plaque psoriasis drugs last year.

"We receive frequent requests for full therapy class reviews to help stakeholders distinguish between the increasingly crowded and overlapping treatments for the various inflammatory conditions," an ICER spokesperson said. "But these assessments tend to be very time- and resource-intensive because of the many interventions and ongoing studies associated with each of the indications, and therefore we look for opportunities to space them out and attach each class review to the launch of a new product for that indication."

Johnson & Johnson filed an supplemental biologics licensing application (sBLA) for Stelara (ustekinumab) in ulcerative colitis with the US Food and Drug Administration in December based on the results of two Phase III trials in patients with moderately to severely active ulcerative colitis. In May, Takeda Pharmaceutical Co. Ltd. also filed a BLA for a subcutaneous version of Entyvio (vedolizumab), which is already approved for UC patients who don't respond to other therapies. Last year, Takeda released top-line data from a head-to-head trial showing Entyvio was superior to AbbVie Inc.'s Humira (adalimumab) in achieving clinical remissions. (Also see "Takeda's Entyvio Beats Humira In Head-To-Head Ulcerative Colitis Trial" - Scrip, 13 Mar, 2019.)

ICER's review, if it proceeds, would presumably also include other therapies approved for UC, drugs such as J&J's Remicade (infliximab) and biosimilars and J&J's Simponi (golimumab).

Evaluating The First NASH Drugs

Another potential high-profile review by ICER would be an assessment of the leading drugs for NASH, a competitive therapeutic area that could see its first drug approval in 2020. Several drug makers are rushing to be first to market. (Also see "NASH Pipeline: Racing To The Finish" - Scrip, 21 Mar, 2019.)

Intercept Pharmaceuticals Inc.'s Ocaliva (obeticholic acid) was the first drug to show an improvement in liver fibrosis without worsening NASH in a Phase III study, and the company has guided investors it will file the drug with the FDA in the third quarter. In addition to Ocaliva, ICER also highlighted Allergan's CCR2/5 antagonist cenicriviroc, which is in Phase III development, and CymaBay Therapeutics Inc.'s selective PPAR delta agonist seladelpar, which recently produced disappointing Phase IIb data. (Also see "CymaBay Alters NASH Hypothesis After Phase IIb Failure In Hepatic Fat Reduction" - Scrip, 11 Jun, 2019.)

ICER said it is also tracking other drugs in the space, like Genfit SA's Phase III elafibranor, and the NASH review could include any of them, based on how their timing aligns with a potential NASH review.

In other highlights, ICER will be continuing its economic analyses of gene therapies with potential reviews of new therapies for beta thalassemia and hemophilia A. It has included bluebird bio Inc.'s Zynteglo (autologous CD34+ cells encoding βA-T87Q-globin gene) for beta thalassemia and BioMarin Pharmaceutical Inc.'s valoctocogene roxaparvovec for hemophilia A on the proposed list.

Neither therapy has been approved yet in the US, although Zynteglo was approved this year in Europe, where bluebird set a price of €1.575m (about $1.77m) over five years, €315,000 annually. (Also see "Bluebird Pushes For Zynteglo Pricing Of Five €315K Annual Installments " - Scrip, 14 Jun, 2019.) BioMarin is hoping to launch its first gene therapy for hemophilia A in late 2020 based on interim results of an ongoing Phase III trial.  (Also see "BioMarin Says It's Got The Hemophilia Therapy Data For Approval And Value " - Scrip, 28 May, 2019.)

ICER's review of Novartis' first gene therapy Zolgensma (onasemnogene abeparvovec-xioi) for spinal muscular atrophy got a lot of attention this year, particularly after the gene therapy was approved by the FDA in May and launched at a price of $2.1m. (Also see "It's Official: Novartis SMA Gene Therapy Zolgensma Is World's Most Expensive Drug" - Scrip, 24 May, 2019.) The cost effectiveness of one-time gene therapies with multi-million dollar price tags and limited long-term data poses a big issue for the industry.

ICER amended its estimate of pricing that would be within a US cost-effectiveness threshold of $100,000-$150,000 per quality-adjusted life year (QALY) for Zolgensma to say a price of $1.1m to $2.1m would be appropriate, based on the FDA approval for presymptomatic population. (Editor's note: this story was updated to reflect a price range of $1.1m to $2.1m after incorrectly stating the range was $1.1m to $1.9m). 

Other notable drugs that could come under scrutiny by ICER next year include: AstraZeneca PLC/Daiichi Sankyo Co. Ltd.'s trastuzumab deruxtecan, an antibody-drug conjugate that has shown improvements in refractory HER2-positive breast cancer patients; Novartis' brolucizumab for wet age-related macular degeneration; Celgene's ozanimod for multiple sclerosis; potential new drugs for sickle cell disease and more (see table).

Flexible Priorities

Of the 18 proposed drugs included on ICER's 2019 agenda, the nonprofit launched assessments on nine of the drugs. There were several changes to the lineup. ICER terminated an assessment of Novartis' canakinumab, for example, after FDA issued a complete response letter, and development/regulatory delays pushed back some drugs on the 2019 list to 2020, including brolucizumab and ozanimod.

ICER also added assessments for conditions that did not appear on the preview list, including Duchenne muscular dystrophy, chronic migraine, opioid use disorder, cardiovascular disease and type 2 diabetes. For example, in April ICER announced it would assess Novo Nordisk AS' oral GLP-1 agonist semaglutide versus currently marketed diabetes drugs. Oral semaglutide is pending at the FDA with action expected in the second half of 2019.

"Our goal is to conclude each of our eight-month assessments of new therapies near the time of FDA approval, and we therefore often need to maintain this sort of flexibility as certain pipeline products accelerate or decelerate through the regulatory process," ICER said.