Celgene’s oral lupus candidate shows ‘trend to improvement’ in small test

Joining many other biopharmas in the difficult race to treat the often-disabling autoimmune condition systemic lupus erythematosus (SLE), Celgene has published data showing its drug has “positive trends” against a dummy therapy.

The phase 2a SLE-001 trial was testing CC-220, its oral immunomodulatory compound that binds to and modulates cereblon in SLE patients (and also being tested in multiple myeloma), with the data being shared at the Annual European Congress of Rheumatology 2017 conference in Madrid, Spain.

Overall, Celgene says that a “trend toward greater improvement with CC-220 treatment compared with placebo in multiple measures of disease activity, as measured by standard scores employed in clinical trials, was observed” in just over 40 SLE patients.

These are not mind-blowing results, though Celgene notes that this particular test was aimed safety, tolerability and pharmacokinetics, with the efficacy endpoints, including changes in Cutaneous Lupus Area and Severity Activity Index (CLASI) and SELENA-SLEDAI score, were “exploratory.”

The Big Biotech said however that this midstage test was good enough to support further work on CC-220 for the disease, were it will likely power its trial toward achieving efficacy.

On the safety side, there were several serious AEs from two patients in the two highest CC-220 doses combined (pneumonia in both cases), as well as two patients in the placebo group. Five patients in the highest CC-220 dose groups and one patient in the placebo group also discontinued due to AEs.

Terrie Curran, president of Celgene’s inflammation and immunology unit, said: “Our work with CC-220 will also help to diversify and deepen our Inflammation and Immunology franchise as we continue to advance CC-220 in the clinic.”

Analysts at Barclays said: “We are encouraged with the early positive data of CC-220 in systemic lupus erythematosus, demonstrating initial clinical efficacy in an asset derived from Celgene’s CELMoD proprietary asset portfolio. If successful this could bolster the growing I&I franchise, currently led by Otezla and ozanimod. We do not believe that these data are enough to move the needle significantly on Celgene's shares, but note that the positive data do contribute to sentiment.”

Analyst Geoff Meacham added: “While we caution that today’s results are early, the initial signs are positive and encouraging, not only for the indication given the unmet need in SLE, but also for the potential of the platform given its rather unique MoA and the company sees opportunities across a number of different therapeutic areas including cancer, I&I, neurodegenerative diseases, and genetic diseases. 

“Given the looming overhang of Revlimid’s loss of exclusivity, we are also encouraged by the company’s efforts to identify longer-term growth drivers. We are reiterating our EW rating, however, until the earlier stage portfolio is sufficiently de-risked." The biotech, which has a market cap nearting $100 billion, was up marginally in mid-morning trading. 

SLE is a difficult-to-treat disease with a number of variations and subpopulations of patients, but one littered with late-stage failures.

A few years ago, GlaxoSmithKline became the first drugmaker in more than half a century to gain approval for a new treatment for the disease in the form of Benlysta.

The drug, a human monoclonal antibody that selectively targets B-lymphocyte stimulator, has however struggled to make much of a sales impact for the company since its FDA approval in 2011.

Benlysta has a license for patients with active, autoantibodypositive SLE who are receiving standard therapy, but brought home just £230 million ($338 million) in 2015.

This is as a result of its modest efficacy, slow onset of action and restrictive label, which has not included patients with severe, active renal and CNS disease. The drugmaker has been undertaking new trials aimed at getting the drug to be used as a subcutaneous formulation.

Other candidates are also in the mix, including UCB’s epratuzumab, although this has failed 2 phase 3 trials. Eli Lilly was working on tabalumab, but this was axed in 2014 after it too failed several pivotal late-stage studies.

Biogen’s anti-BDCA2 antibody is also in early testing, as well as UCB’s dapirolizumab pegol, an anti-CD40 ligand, with Biogen also recently sneaking into its pipeline a new lupus treatment, a Bruton’s tyrosine kinase (Btk) inhibitor known as BIIB068.

Anthera Pharmaceuticals’ blisibimod, which focuses on anti-BAFF activity in LSE, is still going in mid- to late-stage studies. And recently a new startup biotech called Thunderbolt was launched as the brainchild of Baxalta, the Mayo Clinic and Velocity Pharmaceutical Development, with a focus on SLE, also via an anti-BAFF mechanism.

Last August, Aurinia Pharmaceuticals published positive new phase 3 data for its experimental drug voclosporin for active lupus nephritis, but 12 deaths in the study’s treatment arm sent some alarm bells ringing.

The Canadian biotech posted the results for a test that was focused on patients with active lupus nephritis (LN), a form of SLE, which has a number of subpopulations and complications from the broader condition.