I woke to extremely disappointing news this morning. In my Hope for 2016 post, I mentioned peptide based drugs as my #2 hope, with Lupuzor being the key candidate. Over the past several years, I have watched the Lupuzor trials carefully, believing that the drug, if approved for lupus, would offer another off-label treatment option for Sjogren’s Syndrome with an excellent safety profile. The topline results of the final phase 3 Lupuzor trial are out this morning, and it appears that those hopes have been dashed:
- LUPUZOR DEMONSTRATED SUPERIOR RESPONSE RATE OVER PLACEBO IN PRIMARY ANALYSIS ON FULL ANALYSIS SET OF ALL 202 PATIENTS
- SUPERIOR RESPONSE DID NOT ALLOW STATISTICAL SIGNIFICANCE TO BE REACHED (P = 0.2631) AND TRIAL’S PRIMARY END POINT WAS NOT MET
- IN PATIENTS WHO HAD ANTI-DSDNA AUTOANTIBODIES LUPUZOR DEMONSTRATED A SUPERIOR RESPONSE RATE OVER PLACEBO
- STUDY CONFIRMED SAFETY PROFILE OF LUPUZOR WITH ZERO SERIOUS ADVERSE
This is, frankly, terrible news for lupus patients, SS patients, and really the entire community of autoimmune patients. By failing to meet its primary endpoint, Lupuzor will not be approved by regulatory bodies. Essentially, Lupuzor has fallen back to its position in line after its successful phase 2 trial in 2012.
More details have begun to trickle out into the investment media (which is often the best source for clinical trial news). It appears that Lupuzor saw an impressive beneficial result, but the placebo effect may have kept it from reaching statistical significance necessary for a successful trial. The drug performed very similarly to its phase 2 trial results, but the placebo group outperformed its phase 2 results by a noticeable margin:
The data revealed Lupuzor was more effective than the placebo (52.5% versus 44.6%). But because the response rate for those taking the non-active medication plus the “standard of care” was so high the end-point of the study was not achieved… This initial readout was based on 202 patients, including those who withdrew from the trial.
The effectiveness among the 153 that got to the end of the course of treatment was 68.8% (versus 59.2% for the placebo).
In other words, while a healthy 68.8% of the subjects saw benefits from the treatment, 59.2% of those on the placebo + standard of care also saw benefits. While I am not an expert on clinical trials, there is strong evidence that the placebo effect has been increasing in the United States, thwarting the success of clinical trials in many areas. Interestingly, the Lupuzor trial was conducted in six countries outside of the U.S., perhaps indicating that the placebo effect is also increasing in other countries. Unfortunately, the FDA is extremely slow to adapt to changing circumstances, and this is an issue that is likely to remain for some time. This is likley one reason that Bristol-Myers Squibb is conducting its SS abatacept (Orencia) clinical trials in 75 locations across over a dozen countries. There will likely be additional analysis of the failed Lupuzor trials in the coming days and weeks, but it should serve as a warning about the importance of constructing trials with the placebo effect in mind.
So what is next for Lupuzor? There is no denying that an additional phase 3 trial would be expensive and take many more years. Ignoring the placebo results, however, shows a drug that was successful in over two thirds of the patients taking it with zero serious adverse effects. Throwing away those results, as well as 20 years of research and millions of dollars, seems almost criminal. Though cloaked in PR speak, it appears that ImmuPharma would like to continue forward with Lupuzor, but needs more investment dollars:
ImmuPharma said it believes the top line results “provide evidence for the continued investigation into the development and commercialisation of Lupuzor”. It thinks the drug has the potential to offer patients and physicians a much needed effective and safe treatment for lupus.
Following requests from both investigators and patients, ImmuPharma has begun a further study….The plan is to look at the full dataset before making a decision, but the company said there is demand for a new lupus treatment.
It also said there had been “expressions of interest” in the Lupuzor programme and the phase III study.
“ImmuPharma is in ongoing discussions with a number of larger pharmaceutical companies,” it added.
“The results of this study will now be shared with those potential commercial partners. There can be no certainty as to the outcome or timing of these discussions.”
It appears that the best hope is for ImmuPharma to crunch the numbers to show that Lupuzor does have real potential, and for one of the large pharmaceutical companies to agree to fund additional Lupuzor trials, perhaps after an ImmuPharma acquisition. Whether any decide to gamble on Lupuzor in the future remains to be seen. Either way, Lupuzor will not be available as a treatment for Sjogren’s Syndrome patients for years, if ever.
Updated on 4/17/2018
Tim McCarthy, ImmuPharma chairman, gave an interview following the results. You can view the video yourself (it’s about 7 minutes), but the summary is that he feels that Lupuzor still has a lot of promise and he is confident in its efficacy and safety. He notes that several pharma partners have expressed ‘very strong interest’. He also states that ImmuPharma is still in a strong cash position after raising $10 million.
We shouldn’t forget Lupuzor and I do want to emphasize the fact that Lupuzor is still there and we will continue to push it forward… as far as I’m concerned, we still have an extremely attractive drug.