The 3 PD-1 antibody drugs with huge market potential

pd-1 antibodies market potential (Thomas Leth-Olsen

There's been a lot of excitement about PD-1 antibodies in melanoma recently, and data published in the past few days reveals that this excitement is not at all unfounded. But it's not just the therapeutic potential that is causing a stir. According to Reuters, the market potential of the drugs is also expected to be huge.

The PD-1 drugs work by inhibiting a receptor called programmed death 1 (PD-1), an immune "checkpoint" receptor found on T cells. Tumours can produce a protein called PD-L1, which can bind to PD-1 and make the T-cells inactive. PD-1 therefore allows tumour cells to establish a "molecular camouflage". By blocking PD-1, monoclonal antibodies can enhance T-cell responses to attack cancer cells.

Several big pharmaceutical companies are pitting their PD-1 antibodies against each other in a race to be first to market. Here are 3 monoclonal antibodies in contention:

Lambrolizumab (MK-3475) – Merck

  • Interim data published in New England Journal of Medicine, and presented at ASCO this weekend, showed (press release):
    • Overall response rate (percentage of patients who experienced tumour shrinkage) was 38%, out of 135 patients with advanced melanoma
    • In a subset of patients at the highest dose, the response rate was 52%
  • "Based on these data and additional findings from our ongoing studies, Merck plans to initiate late-stage clinical trials of lambrolizumab in advanced melanoma, and non-small cell lung cancer in the third quarter of 2013," said Roger M. Perlmutter, M.D. Ph.D., president, Merck Research Laboratories (press release)

Nivolumab Bristol-Myers Squibb

  • Follow-up findings from the CA209-003 phase I trial showed (OncLive):
    • Overall response rate was 31%, out of 107 patients with stage IV melanoma
    • In a subset of patients, the response rate was 41%
  • Combination of nivolumab with Yervoy (a BMS immunotherapy already on the market) had an overall response rate of 40%, with a subset of patients showing a response rate of 53% (press release)

MPDL3280A Roche Genentech

  • This drug works slightly differently as it doesn't block PD-1, but rather it blocks PDL-1.
  • Overall response rate was 21%, out of 140 patients with non-small cell lung cancer, melanoma, kidney cancer, colorectal cancer, and gastric cancer (Yale News)

Of course, it's hard to compare the above data to establish which drug is "best", as you'd be comparing tumour shrinkage across multiple trials. Although the drugs are still in their early stages, the PD-1 drugs seem extremely exciting, and there is understandably a large amount of optimism surrounding their development. With regard to the Merck results, Dr. Antoni Ribas, a professor of medicine at the University of California, Los Angeles, and the senior author of the study, said "This is the most impressive thing I've seen in melanoma. We've never had something where we've had these rates of responses with these minimal side effects." (NY Times)

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The drugs are projected to reach billions of dollars in annual sales, subject to further testing and regulatory approval, of course. Nivolumab alone is expected to have sales of $1.2 billion in 2017, according to Wall Street analysts tracked by Thomson Reuters Pharma (Reuters). And the PD-1 drugs aren't just for melanoma, either. According to Reuters, Bristol-Myers has three late-stage clinical trials of nivolumab in melanoma, two late-stage trials in lung cancer and one in kidney cancer, while Merck is studying lambrolizumab in triple-negative breast cancer, head and neck cancer, bladder cancer and lung cancer (Reuters).

What do you think? Are you excited by PD-1 antibodies? Do you think they will be the next big blockbusters? Join our discussion on LinkedIn, or leave a comment below. Want more from Total BioPharma? Sign up to our newsletter – it doesn't cost anything and only takes a minute.

If you want to know more about mAbs, ADCs and next generation technology, you might be interested in attending the 9th Annual European Antibody Congress 2013, 11-13 November 2013, Geneva.

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