2015 Pipeline Report: Burning Bright

Dec 12, 2014

Tracking new therapies as they wind their way through development, regulatory approval, and payer acceptance can be like waiting for paint to dry and then repainting in a different color. It's a slow process and far from linear.

Josh Baxt
This is especially true for potentially groundbreaking drugs, disruptive technologies that completely upend markets and patient care. The lag time between that first flickering glimmer of hope and an accepted therapy can be measured in decades. And, all too often, agents that seem hopeful in the lab and early clinical trials fizzle on further investigation.

But then there are those rare moments when the stars align and truly astounding therapies make their way into the world, providing improved care and big returns. In the next few years, cancer immunotherapies seem likely to enter the pantheon of big winners. And they may not be alone. Besides the buzz around a cure for hepatitis C virus, there are exciting drugs for heart failure and cholesterolemia coming into play. On a smaller scale, companies are embracing new therapies for rare diseases. Stem cells are making real forays into late-stage trials.

This year's pipeline report will check in on these emerging technologies, as well as potential therapies to address metabolic and neurodegenerative diseases. There's a lot to like in the pipeline and more than a little competitive drama to make it really interesting.

Immuno-oncology: The elegant solution

For Trekkers, there's nothing better than watching a Klingon or Romulan ship lose its invisibility cloak and get blasted out of space. On the cellular level, similar action is driving the excitement around programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) checkpoint inhibitors: the opportunity to reveal cancer and unleash the immune system against it.

"There's genuine enthusiasm among oncology experts," says Seamus Fernandez, managing director of Major and Specialty Pharmaceuticals at Leerink Partners. "There's evidence of activity in more than five different tumors and signals of activity in as many as 14. We forecast a $36 billion immuno-oncology market by 2025."

That's a large pie and there's been a lot of jostling to get the biggest piece. Bristol-Myers Squibb's cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitor Yervoy (ipilimumab) was first out of the gate, but there are several other agents poised to hit the market.

In September, Merck's PD-1 blocker Keytruda (pembrolizumab) received accelerated approval from the FDA to treat melanoma and the company is researching the drug against non-small cell lung cancer (NSCLC) and other indications. In its World Preview 2014 Outlook report, EvaluatePharma forecasts Keytruda sales of $4.06 billion by 2020.

That's a great start, but it's unclear whether Merck's advantage will hold out over the long haul. The competition will be fierce in the PD-1/PD-L1 space. With the huge potential market, this could be the equivalent of the Oklahoma land rush for the usual pharma titans. However, Stephanie Hawthorne, senior director at Kantar Health, notes that, for now in melanoma, Merck is in the driver's seat compared to BMS's PD-1 inhibitor Opdivo (nivolumab), which is a few months (or possibly longer) behind Keytruda in the US.

"It's a big advantage for Merck being first-to-market," says Hawthorne. "Based on the available data, they both look really efficacious, and they're fairly well tolerated compared to Yervoy. BMS's saving grace might be the combination of Opdivo and Yervoy they are studying. The survival data we've seen for it so far is really impressive, and that could trump Merck's lead."

Hawthorne's point was underscored in late September when BMS released data at the European Society for Medical Oncology (ESMO) showing that Opdivo achieved a 32% response rate against advanced melanoma in patients who had previously been treated with Yervoy. The control group, which received traditional chemo, had an 11 % response.

While Keytruda was first in the US, Opdivo was approved for melanoma in Japan in July, under a deal with BMS partner Ono Pharmaceuticals. The ESMO data will only support BMS's showing in the US. The FDA has given Opdivo fast track designation in NSCLC, melanoma, and renal cell carcinoma (RCC) and breakthrough therapy designation for Hodgkin's lymphoma. In September, BMS announced that both the FDA and European Medicines Agency (EMA) have accepted Opdivo for accelerated review for melanoma. The FDA PDUFA date is March 30, 2015.

"Opdivo is the most valuable pipeline drug in development at the moment," says Lisa Urquhart, editor of Evaluate's editorial team, EP Vantage. "The data from studies is showing some impressive advances in both overall survival and disease progression."

EvaluatePharma pegs Opdivo's potential sales at $6 billion by 2020. The company believes Opdivo could be approved for melanoma in the US next year. Meanwhile, Hawthorne expects approval for the Opdivo/Yervoy combination in early 2016.

That's in melanoma. Opdivo may even have a more clear-cut advantage in being first-to-market for NSCLC, where BMS has already submitted its drug for approval while Merck is still completing Phase III trials.

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