JPM25: Vertex CEO says pain is its next multi-billion franchise

Vertex's leaders projected confidence in the firm's non-opioid pain franchise at the JP Morgan Healthcare Conference on Monday, although the first cut of data for lead candidate suzetrigine in peripheral neuropathic pain (PNP) had left investors disappointed in December. 

While the Phase II sciatica study met its primary endpoint with suzetrigine showing significant pain reduction compared to baseline, the oral NaV1.8 inhibitor held no significant advantage over placebo, casting doubt on its potential for chronic pain treatment (see – Spotlight On: Sciatica setback magnifies doubts about Vertex’s suzetrigine in chronic pain).

CEO Reshma Kewalramani and Chief Scientific Officer David Altshuler suggested during the company's JPM presentation that an outsized placebo response influenced the results, but that such an effect is manageable moving forward — even hinting that the planned Phase III study for suzetrigine will feature a slightly different study design than the Phase II study. 

Lessons learned

"The efficacy was as expected, the safety was as expected, but the placebo was larger than expected," Altshuler said of the results, which triggered a 10% drop in vertex shares when they were announced. "We can learn from that data, we can work on the design of the study, and work with regulators to bring forward the medicine… we feel confident it is the best opportunity for patients," he added. 

Kewalramani echoed the sentiment, adding that managing a placebo effect is "part and parcel" of developing a pain therapeutic. 

"If you are going to work in the pain space, you have to learn how to deal with the placebo effect," she said. "Part of it is coming up with better medicines, and we are well on our way of doing that… and the second half is learning how to do clinical trials where you can manage the placebo effect. If anyone can do it, I’d bet my money on team Vertex." 

Kewalramani described Vertex's approach in pain as akin to its lucrative and highly effective portfolio of cystic fibrosis (CF) drugs, which involved a series of approvals for medications that have improved upon each other in terms of efficacy and addressable patient population with each iteration. The company's first  CF drug, Kalydeco (ivacaftor), was approved in 2012 and its most recent, the triplet therapy Alyftrek (vanzacaftor/tezacaftor/deutivacaftor), came in December. The company is expecting $10 billion in total revenue from its CF portfolio in 2024.

Coming up behind suzetrigine, Vertex has VX-993, a next-generation NaV1.8 inhibitor in Phase II testing for acute pain and PNP. The company also has additional NaV1.8 inhibitors in preclinical development, as well as NaV1.7 inhibitors that Kewalramani said could be dosed as either a monotherapy or in combination with other pain candidates.  

Beyond deploying a similar step-wise development strategy as CF, Vertex thinks pain could hold a similar profitability. "We believe we can build another multi-billion franchise," Kewalramani said.

Although suzetrigine hit a stumbling block in PNP, the NaV1.8 inhibitor seems to have proved its mettle in acute pain and is nearing an expected approval on Jan. 30. 

Pricing insights

Chief Operating Officer Steve Arbuckle shared some insight into Vertex's pricing strategy for suzetrigine, and the drug's non-addictive nature may factor heavily into its cost. The company projected that opioid-use disorder costs the US economy about $180 billion annually, with $10 billion to $20 billion attributable to opioids prescribed for acute pain. 

"We are going to be in this market for decades to come, and the price of suzetrigine will set the value for this franchise for many years to come," Arbuckle said. The pricing will be "in that sweet spot that allows us to get access for patients, whilst at the same time, reflects the clinical value of the cost offsets that it will have in terms of reducing the opioid epidemic here in America, but also reflects the significant investment we've made over literally decades to get to this point."