June 2, 2015
By Alex Keown and Riley McDermid, BioSpace.com Breaking News Staff
LONDON -- Within the next few weeks England-based AstraZeneca PLC will decide whether or not to independently pursue an experimental psoriasis drug that has been linked to suicidal side effects, Bloomberg reported this morning.
“We want to take more time to look at the data and take time to engage with regulators,” AstraZeneca’s Chief Executive Officer Pascal Soriot told the news service. “We are actively contacting people who can help us think our strategy through, if we can find a way forward or not.”
Since 2012 AstraZeneca and California-based Amgen have been jointly working to commercialize five monoclonal antibodies from Amgen‘s clinical inflammation portfolio, including brodalumab, an investigational IL-17 inhibitor, which is in development for patients with moderate-to-severe plaque psoriasis, psoriatic arthritis and axial spondyloarthritis.
However, on May 22 Amgen stepped away from the agreement concerning brodalumab after patients showed signs of suicidal tendencies, which would require a stringent warning label if the drug achieved regulatory approval. During trials, for patients showed suicidal tendencies and two patients committed suicide. When Amgen announced it was terminating the collaboration, the company also said there were additional suicides in the open label extension studies, beyond the two reported in the Phase III studies.
Brodalumab belongs to a class of drugs called IL-17 inhibitors, which blocks the binding of several IL-17 cytokines to the receptor. The IL-17 receptor and cytokine family play a central role in development and clinical manifestations of plaque psoriasis.
When Amgen terminated the agreement the company said the regulatory labeling that would likely be required for the psoriasis treatment would “limit the appropriate patient population.” Amgen said it will focus its efforts on other “key molecules that address unmet medical needs.” The company said is does not expect any meaningful negative financial impact from its decision to withdraw from the development of brodalumab.
Amgen (AMGN) likely scuttled the deal with AstraZeneca PLC (AZN) after the suicide development meant the drug would likely require restrictive labeling, if it were eventually approved by regulators. The news is a major blow to both companies, who had predicted the drug could eventually rake in $500 million and $1.5 billion in sales annually.
“During our preparation process for regulatory submissions, we came to believe that labeling requirements likely would limit the appropriate patient population for brodalumab,” said Sean E. Harper, executive vice president of Research and Development at Amgen, in a statement at the time.
The company said it would no longer be involved in the development of brodalumab, though there was some indication AstraZeneca may continue to advance the program.
“After Amgen transitions the program to AstraZeneca, future decisions on the clinical development and submission of marketing applications for brodalumab will be at the sole discretion of AstraZeneca for all territories, except for certain Asian territories, including Japan, where Kyowa Hakko Kirin has rights to brodalumab,” said Amgen.
Despite the setback, AstraZeneca is not moving to cease research on the drug. Following the termination of the collaboration, Soriot, AstraZeneca’s chief executive officer, said the company wanted to take some time to look at the data and talk things over with regulatory authorities and see if there is a clear path forward to bringing the drug to market.
A warning label could limit revenues, especially considering Novartis AG already markets a similar psoriasis drug called Cosentyx that does not come with suicidal side effects. Eli Lilly and Company is also developing a psoriasis drug, ixekizumab. Although still in Phase III trials, ixekizumab patients have not shown an increase in suicidal thoughts, analysts said.
If brodalumab is permanently shelved, it could impact AstraZeneca’s goal of achieving $45 billion in sales by 2023, although Soriot dismissed the notion. In his interview with Bloomberg he said the overall sales goal has risk probability built in regarding the company’s pipeline. The company reported $26 billion in revenues last year.
Forecasts for the program had been sunny and the latest news came as a stunning blow, said several analysts. In November, Amgen (AMGN)’s announcement that the drug saw Phase III results making it superior in some aspects to main competitor Stelara were seen as a huge boon for the company, said Bret Holley, a biotech analyst with Guggenheim Securities, in a note to investors at the time.
On Nov. 11, Amgen announced top-line brodalumab results from its Phase III AMAGINE-3 trial in moderate/severe plaque psoriasis. That data showed brodalumab demonstrated superior efficacy on all endpoints, including, most notably, superior efficacy of achieving total clearance of skin disease, as measured by the Psoriasis Area Severity Index (PASI 100).
“We believe the PASI 100 results will be differentiating for brodalumab, based on a striking 36.7 percent for 210 mg and 27 percent for 140 mg brodalumab, versus 18.5 percent for Stelara and 0.3 percent for placebo,” wrote Holley in a note to investors. “With this outcome, we believe Amgen will be able to effectively position high-dose brodalumab versus. Stelara and the anti-TNFs in psoriasis.”
Holley said even more importantly, brodalumab’s safety profile appeared comparable to Stelara in the top-line results, with an SAE rate of 1.4 percent, 1.6 percent and 0.6 percent for 210 mg brodalumab, 140 mg brodalumab, and Stelara, respectively.
“Based on positive results from Phase III AMAGINE-1 trial of brodalumab in psoriasis, we had expected a positive outcome from AMAGINE-3, but we believe brodalumab’s superiority over Stelara is a clear win for Amgen,” said Holley. “Amgen expects results from a third Phase III brodalumab psoriasis trial (AMAGINE-2) by year end 2014, and we believe these results will further underscore the drug’s superior efficacy versus Stelara.”
Will PfizerKline Become the Next Pharma Player?
The speculation surrounding a possible bid from Pfizer Inc. for struggling GlaxoSmithKline is heating up, after one closely-watched biotech analyst said in a note last week that Pfizer buying the company would “unlock access to its balance sheet and improve its tax situation.”
Gregg Gilbert, a biotech analyst at Deutsche Bank, wrote in a note to investors “Introducing PfizerKline” that he thinks a deal would be “materially accretive” for both companies. Gilbert estimated that a bid priced at $29.86 a share, via half stock and half cash, which would push up Pfizer’s earnings per share by 10 percent to 16 percent beginning in 2016.
“We believe that the company has a sense of urgency to create value by leveraging the power of its balance sheet to do needle-moving deals,” Gilbert wrote. “Since media reports in the past have pointed to the potential for a Pfizer/GSK combination, we are revisiting that theme.”
We want to know, dear readers, if you agree? Should Glaxo continue going it alone, or might Pfizer buy it and create one of the world’s largest pharma players in history?
