Celgene's Revlimid Faces A New Obstacle

| About: Celgene Corporation (CELG)

Summary

Celgene has announced that its blockbuster agent, Revlimid, did not improve overall survival in patients with DLBCL when used as maintenance therapy.

The REMARC study was terminated as a result, leaving a hole in the pipeline for Revlimid.

Celgene is continuing to develop Revlimid for other treatment settings in DLBCL.

Celgene (NASDAQ:CELG) scored a huge hit with its orally dosable immunomodulatory drug lenalidomide (Revlimid), and since its first approval for myelodysplastic syndromes in 2005, the company has come to rely on Revlimid sales to fund operations and for revenue growth.

Subsequent approvals in mantle cell lymphoma and multiple myeloma were assumed to be precursors to a major annexation of market share within oncology, and CELG started up trials across a variety of hematologic malignancies.

The News

Many hopes that diffuse large B-cell lymphoma (DLBCL) would be the next domino to fall for CELG. Since it is the most common form of aggressive non-Hodgkin lymphoma, Revlimid could have made a serious impact.

The most powerful push by CELG for the drug was the REMARC study, a phase 3 trial comparing Revlimid and placebo in elderly patients with DLBCL. Revlimid was tested in the so-called maintenance setting, which means they would receive the drug as a sort of low-intensity booster for a period of time after initial chemoimmunotherapy.

Early findings looked quite promising, with an improvement in progression-free survival attributed to Revlimid. Unfortunately, a press release on July 25 indicated that the drug did not improve overall survival.

In this treatment area, a lack of improvement of overall survival is a death knell, especially for a drug like Revlimid that is associated with certain unfavorable toxicities, such as neutropenia deep-vein thrombosis.

The Fallout?

This is certainly a setback for CELG in DLBCL, but I think we can take away two points from this news.

  1. It affirms that one must be careful when analyzing clinical trial data. Some companies will report improvements in progression-free survival, and it is important not to make rash investment decisions based on these kinds of endpoints. As you can see, it does not always translate into benefit, however counterintuitive that may seem!
  2. CELG is not dead in the water in non-Hodgkin lymphomas. In fact, the company has not stopped development in DLBCL. ROBUST is a phase 3 study evaluating Revlimid versus placebo when added to chemoimmunotherapy (a combination of the CHOP regimen and rituximab) for untreated DLBCL of a specific molecular subtype: ABC. This subtype of DLBCL is associated with worse outcomes than its counterpart, GCB.

What's more, an earlier phase 2/3 trial provided key early data about the potential efficacy of Revlimid in this setting. At ASH 2014, CELG showed that overall response rate, progression-free survival and overall survival were all substantially improved using Revlimid compared with investigator's choice in relapsed/refractory DLBCL, but only for patients with ABC-type disease.

In the HEM-0835 study, addition of Revlimid to R-CHOP improved the 2-year rates of progression-free and overall survival, but only in patients with non-GCB molecular subtypes. This further supports the idea that only ABC-type patients are seeing substantial benefit from the drug.

Conclusions

So, CELG is not done with DLBCL by a mile. The preliminary findings we have access to suggest that Revlimid could make a serious impact in a poor-prognosis form of the disease. It remains to be seen whether addition of Revlimid will lead to unacceptable increases in toxicity, and we'll also want to watch the efficacy data carefully.

All in all, don't count out the possibility that CELG can grow the drug's sales through approval in DLBCL. This story is not finished. We should be able to expect data from the ROBUST trial sometime in 2018, most likely.

In the meantime, the company is also continuing aggressive exploration of Revlimid in other forms of non-Hodgkin lymphoma, and I think we can expect these data sooner, perhaps as early as ASH 2016. If not, then we should definitely see results from trials like AUGMENT (relapsed indolent disease) and RELEVANCE (follicular lymphoma) sometime in 2017.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.