Bristol-Myers, Alder Drug for Rheumatoid Arthritis Passes Key Test
Four years ago, the CEO of Bothell, WA-based Alder Biopharmaceuticals declared that his company’s experimental rheumatoid arthritis drug would someday give multibillion-dollar products from Amgen and AbbVie a “run for their money.”
Today, some more clinical trial data trickled out to suggest that Alder’s partner, Bristol-Myers Squibb, is maneuvering into a position to compete in the next few years.
New York-based Bristol-Myers (NYSE: BMY) said today that an experimental drug licensed from Alder, called clazakizumab or “claza” for short, met its goal of reducing rheumatoid arthritis pain and symptoms in a mid-stage clinical trial of 418 rheumatoid arthritis patients. People on the lowest dose of the once-monthly injectable drug from Bristol-Myers and Alder did better than those on higher doses of the same drug, and overall response rates on the low dose were similar to those seen among patients who got AbbVie’s adalimumab (Humira), the world’s best-selling pharmaceutical.
On a couple of different scoring systems, roughly twice as many patients on the Bristol/Alder drug went into remission, when compared with the AbbVie drug, researchers said. About 8.3 percent to 13.3 percent of patients on varying doses of the new Bristol-Myers/Alder drug reported some form of serious side effect, compared with 5.1 percent for those on the standard 40 milligram dose of the AbbVie drug. Results were reported today at the American College of Rheumatology meeting in San Diego. (See the full study abstract, with data tables, here).
“We think this drug offers promise to help more patients with RA to get into disease remission,” says Pushkal Garg, Bristol-Myers’s vice president of immunoscience development. “About 70 percent of patients treated today don’t get into remission. It’s our aspiration to put more of them into remission.”
Bristol-Myers obtained the worldwide commercial rights to the Alder drug, formerly known as ALD518, for non-cancer uses back in November 2009 for $85 million upfront and potentially $1 billion in future milestone payments. The Alder drug is an antibody designed to tamp down excessive inflammatory reactions by binding with a protein molecule known as IL-6. The drug is a “fast-follower” behind another antibody, Roche’s tocilizumab (Actemra), which works a bit differently, by specifically binding with a receptor on IL-6.
The new category of IL-6 inhibitors also represents a new way of treating autoimmune diseases, beyond the class of drugs that work by inhibiting another protein called TNF, the target of Amgen’s etanercept (Enbrel) and AbbVie’s adalimumab (Humira). While those drugs have been hugely lucrative—AbbVie’s product generated $9.3 billion in worldwide sales alone in 2012—they don’t work for everybody. The Alder antibody is also made in a yeast-based production system that’s supposed to be faster and cheaper than other biotech drugmaking platforms, so it’s conceivable that if its drug wins FDA approval, Bristol-Myers could charge a lower price and still maintain a high profit margin on par with the anti-TNF drugs. The Bristol/Alder drug could also offer a convenience advantage, in that it is delivered in a once-monthly injection, while the AbbVie product requires an injection every other week.
Alder and Bristol-Myers reported on some promising clinical results with their drug three years ago at the European League Against Rheumatism (EULAR) meeting, but that was with an earlier-generation antibody designed to be given through an intravenous infusion. Since the market-leading drugs are given as subcutaneous injections that patients can give themselves just under the skin, the Bristol-Myers/Alder drug had to be made into a similar subcutaneous formulation to be competitive.
The results reported today are from a randomized Phase 2b study that examined a variety of doses with the new subcutaneous form of the drug.
Here’s how the study was set up:
Patients in this study were randomly assigned into one of seven cohorts with about 60 people each. One group got a placebo plus methotrexate (a common generic immune suppressor), and another group got AbbVie’s adalimumab (Humira) with methotrexate. The other patients got the new Bristol-Myers/Alder drug in either a 25 mg, 100 mg, or 200 mg form, with or without methotrexate.
Here’s what researchers found: Patients appeared to do the best on the lowest dose (25 milligrams) of the Bristol-Myers/Alder drug. The drug met the study’s main goal, by showing it could help many more patients achieve a 20 percent reduction in the signs and symptoms of rheumatoid arthritis, as measured by the standard ACR20 scoring system after 12 weeks. About 78 percent of patients on the low 25 milligram dose of Bristol-Alder’s claza and methotrexate reached the ACR20 threshold, while 39.3 percent did that well on methotrexate and a placebo. The new drug performed almost identically to the existing product sold by AbbVie. About 76.3 percent of patients reached the ACR20 goal on the standard 40 mg dose of the AbbVie drug and methotrexate.
While the primary goal of the study is always important to watch, researchers also looked at a number of important secondary goals. They looked at the number of patients who had a 50 percent reduction in their signs and symptoms (ACR50) and the number who did truly fantastic, achieving a 70 percent reduction (ACR70). As readers can see from the study abstract, the Bristol-Myers/Alder drug was again very similar to the AbbVie drug on the ACR50 score (47.5 percent compared with 49.2 percent), and appeared to have a slight advantage on the ACR70 score (27.1 percent to 18.6 percent). The Bristol-Myers/Alder drug appeared to have some more advantage on a couple different ways of measuring disease remission, particularly what’s known as Disease Activity Score 28 (DAS28), which measures levels of C-reactive protein in the blood.
The new biotech drugs that work by blunting an excessive immune reaction are also associated with an increased risk of infection, so that is something researchers always look carefully at in clinical trials. The most common side effects associated with the new drug were dose-related injection site reactions that ranged from 32.2 percent of patients up to 63.3 percent of patients, according to a Bristol-Myers statement. Between 1.7 and 5.1 percent of patients on various doses of the new drug reported serious infections during the study, compared with none in the methotrexate-only group, and 3.4 percent who got the AbbVie drug and methotrexate. Patients on the new drug also saw increases in their total cholesterol scores, although that’s a predictable effect based on IL-6 inhibition, Garg said. Bristol-Myers didn’t say how much the cholesterol scores went up.
Bristol-Myers also didn’t say in today’s statement what its next move will be in clinical development. Garg said the company is going through the data “with a fine-tooth comb” to map out its next steps in clinical trials. But he suggested the drug clearly has a future in Phase III clinical trials, the largest and most expensive stage of development before FDA approval. The new IL-6 inhibitor, he said, could end up “building on the foundation we’ve built” with abatacept (Orencia), which works against rheumatoid arthritis through a different scientific mechanism, by blocking T-cell co-stimulation.
“We’re very excited about the results with claza, and we’re mapping out next steps,” Garg said.
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