- Global Blood Therapeutics Inc. is no longer developing its main candidate as a treatment for idiopathic pulmonary fibrosis (IPF) after three studies showed the drug doesn't provide a significant benefit for patients with the rare lung disease.
- Data from the Phase 1 Basecamp trial and a pair of Phase 2 investigations, dubbed GBT440-006 and ZEPHYR, reaffirmed GBT440's safety profile and ability to increase oxygen levels in the blood, according to a Monday statement. While some of the IPF patients taking Global Blood's drug had significantly improved oxygen saturation, investigators didn't observe clinically meaningful benefits overall.
- Shares in the South San Francisco, California-based drugmaker opened at $30.50 apiece on Monday, down more than 6% from Friday's close of market.
Rare disease drug development has become a focal point for the pharmaceutical industry in recent years. An October report from QuintilesIMS noted that the Food and Drug Administration has approved more than 130 orphan medicines in the last five years, while the U.S. healthcare system spent $36 billion on those treatments in 2016.
IPF is a prime example of a rare disease that has captured drugmakers' attention. Though the condition affects just a couple dozen people for every 100,000 — according to estimates cited by the National Organization for Rare Disorders — it has become a highly lucrative therapeutic area. Boehringer Ingelheim's Ofev (nintedanib), for example, fetched €613 million ($652 million) worth of sales last year.
It looks like, at least for now, that's a market Global Blood won't be tapping into. During an Oct. 23 investor call, CEO Ted Love indicated the company's most clear path forward is continued development of GBT440 in sickle cell disease.
"We definitely have learned a lot and we think we'll learn more by studying the data, but we have concluded that we're going to keep GBT440 focused on sickle cell disease," Love said. "We have other molecules that we could theoretically bring back into other indications, but we definitely have not made a decision to do that at this stage."
Global Blood hit the NASDAQ in 2015 after a lucrative $120 million initial public offering. Across 2015 and 2016, the company spent nearly $8.2 million researching GBT440 in hypoxemic pulmonary disorders, according to its most recent 10-K filing with the Securities and Exchange Commission.
The Basecamp, GBT440-006 and ZEPHYR studies collectively enrolled very few patients — each ranged from about 15 to 30. Basecamp evaluated GBT440 in healthy participants who were under hypoxic conditions, whereas the mid-stage trials tested the drug in IPF patients. Notably, ZEPHYR enrolled adults with more severe forms of the disease.
Unfortunately for Global Blood, the healthy volunteers appeared to be the only ones who had statistically significant benefits to oxygen saturation at lower doses of GBT440. In GBT440-006, patients taking 1,500 mg of the drug also demonstrated significantly improved oxygen saturation, yet didn't show physical signs of their disease getting better.
"We were not seeing transformative signals of clinical benefit which we had hoped to see. We were seeing an improvement in [oxygen saturation], but only once we got to 1,500 milligrams, and so we were seeing the mechanism of action, but we weren't seeing the clinical benefit," Love said, adding that the company will present more detailed data at a later date.
Love and Josh Lehrer, Global Blood's SVP of clinical development, also fielded questions on why their drug failed in the IPF setting and what implications that may have for the sickle cell indication.
"We're obviously speculating at this stage, but we think it likely relates to the impaired oxygen exchange, which is a primary problem in their disease," Love said regarding GBT440's performance in IPF patients. "GBT440 is of course not impacting the underlying disease, it's simply trying to pull oxygen across the diseased lungs and it looks like, based on the differences between what we saw in Basecamp and [GBT440-006], that the lung fibrotic process itself is limiting the effect of 440."
In spite of the setback, Love remained optimistic about the drug's prospects.
"The thing you're always concerned about in small molecule development is your safety profile, so any time you study a population — particularly a population like IPF where patients are terminal and very sick — you really worry about your safety profile," he said.
"We were particularly encouraged that, even in this very sick, co-morbid patient population that the safety profile of 440 continues to be consistent with what we previously described," he added.