Takeda takes on multiple myeloma outcomes study, as Ninlaro flounders

red blood cells

Patient outcomes in multiple myeloma have been improving in recent decades. This is a trend that’s expected to continue, with several recent FDA approvals that are creating increasingly effective and complex combination treatments. A massive, new 5-year observational study from Takeda Pharmaceutical, which last November gained the first FDA approval for an oral proteasome inhibitor to treat multiple myeloma with its Ninlaro (ixazomib), is aiming to establish a new benchmark.

At least so far, Ninlaro isn’t quite living up to the long-standing, high expectations for an oral proteasome inhibitor in multiple myeloma. In May, the EMA’s CHMP offered a negative opinion, thereby blocking any EU introduction unless it reverses its decision during the ongoing review that Takeda requested in June.

The agency rejected it on the grounds that the subgroup data didn’t offer compelling evidence that the candidate was more effective in more difficult to treat disease. The proposed indication had been in patients with two prior treatments whose disease returned.

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"Takeda has appealed the CHMP’s negative opinion of NINLARO and requested a re-examination," Takeda Oncology VP of U.S. Marketing Ryan Cohlhepp told FierceBiotech via email. "We have confidence in the merits of appealing; however, there is no guarantee that it will result in a different opinion. We expect additional data from the TOURMALINE program to be available in 2017 to further support our filings for Ninlaro."

In addition, Takeda reported only $58.3 million in Ninlaro sales during the second quarter, which was its second full quarter of sales. The drug is still expected to fulfill blockbuster sales expectations of about $3 billion a year at their peak, according to the company. But its steep price tag of a reported $8,670 per four weeks may be too high to make it viable against a generic Velcade, which could come as early as next year.

Takeda remains upbeat about the launch despite the early sales. "The launch of Ninlaro in the U.S. is proceeding quite well, with early indicators pointing toward a strong launch. Through July, our data shows that Ninlaro has captured approximately 20% of the second-line market, the highest share of any new therapy," Cohlhepp said.

The oral Ninlaro is intended to as a replacement for injectable Velcade. Likely in an effort to make a more targeted appeal, Takeda recently started working with the Broad Institute to do a genomic analysis of its Ninlaro Phase III trial subjects.

Measuring MM

The new study could help the pharma to better understand the role of Ninlaro in combination treatment as part of any bigger picture insights. The company already has started enrolling patients in the noninterventional, observational 5,000-patient, 150-site global study, INSIGHT-MM. The idea is to monitor and establish patterns in disease presentation, patient characteristics, treatment and outcomes that can better inform how patients are treated.

The open-source, collaborative study has already started at a trio of U.S. locations: University of Arkansas for Medical Sciences; the University of California, San Diego; and the University of Cincinnati Cancer Institute. It is focused on newly diagnosed, as well as relapsed/refractory multiple myeloma patients.

“As both a physician and a patient, I have seen--and experienced--rapid changes in the approach to multiple myeloma treatment. Even with the recent introduction of new therapies, more work needs to be done to improve outcomes for patients across the globe,” said Dr. Jim Omel, an INSIGHT-MM Steering Committee member who was diagnosed with multiple myeloma in 1997, in a statement. “The INSIGHT-MM study gives the community an opportunity to work together to better understand how clinical advances affect multiple myeloma patients in the real world.”

Five-year survival rates for multiple myeloma patients after diagnosis have improved rapidly in less than two decades--from about one-third during 1998 to 2001, to almost one-half--a figure based on data from 2006 to 2012. The suspicion is that broad-based patient outcomes have improved even further with treatment advances in recent years.

“Given the increased complexity of treatment in recent years, we saw the need to understand treatment patterns and patients’ experiences around the world,” said Takeda Oncology VP of Global and US Medical Affairs Liviu Niculescu. “With patients and multiple myeloma experts, we designed the innovative INSIGHT-MM trial to be an open source of data--large enough to reveal differences and trends globally. We invite collaborations from other similar studies in order to increase the size of available databases.”

New MM combos

Takeda acquired Ninlaro, along with injectable proteasome inhibitor Velcade (bortezomib), when it bought Millennium Pharmaceuticals in 2008 for $8.8 billion; it’s approved for use alongside a standard-of-care combo known as Rev-dex, Celgene’s Revlimid (lenalidomide) and dexamethasone (a generic corticosteroid). That’s after the use of at least one prior treatment.

Amgen ($AMGN) has its own oral proteasome inhibitor--oprozomib--which is still only in Phase Ib testing; that’s thought to be due to an ongoing reformulation effort to reduce its toxicity as compared to ixazomib. The biopharma gained oprozomib, as well as the then newly approved multiple myeloma treatment Kyprolis (carfilzomib), when it bought Onyx Pharmaceuticals in 2013 for $10.4 billion.

In addition to Ninlaro, the FDA approved at least three other novel multiple myeloma treatments last year: Novartis’ Farydak (panobinostat), which was the first histone deacetylases (HDAC) inhibitor approved to treat the disease, Johnson & Johnson’s Darzalex (daratumumab), the first monoclonal antibody approved to treat multiple myeloma, and Bristol-Myers Squibb’s immunotherapy treatment Empliciti (elotuzumab).

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