It’s happened before.

For many in the Massachusetts biotech community, the buyout buzz surrounding Biogen Inc. has revived vivid memories of other homegrown heavyweights, notably Genzyme Corp. and Millennium Pharmaceuticals Inc., being snapped up by out-of-state pharmaceutical giants.

A purchase of Biogen — which was approached by Merck & Co. and Allergan PLC, according to The Wall Street Journal — would likely mean the loss of local control for the state’s largest remaining biotech and most valuable public company.

“It would be the end of an era,’’ said life sciences adviser Leora Schiff, principal at Altius Strategy Consulting in Somerville. “Biogen is the last of the industry’s early trailblazers. Genzyme is no longer independent, Millennium is no longer independent. We could be losing that culture of entrepreneurial risk-taking. Control over the company’s direction would shift out of state, and that could have an impact on workforce levels and where research is done.’’

Biogen’s stock climbed 9.3 percent to a 2016 high on Tuesday after the Journal reported the takeover overtures. The shares gave back 2.7 percent on Wednesday to $321, as analysts debated the likelihood that an offer would be made.

The importance of corporate headquarters to Massachusetts was highlighted by the successful pursuit of General Electric Co. by the Baker and Walsh administrations, said economist Barry Bluestone, director of Northeastern University’s Dukakis Center for Urban and Regional Policy.

“I would expect whoever acquired Biogen would continue to have a large presence in Massachusetts because this is a major research center,’’ Bluestone said. “But there would be less loyalty to the community, and when decisions are made on where to locate operations, they would be made somewhere else.’’

For now, there is only speculation on Biogen’s fate. The company has yet to receive a formal offer, and some analysts have suggested its recent stock run-up and its market value of more than $70 billion make it an expensive takeover candidate.

“It may be wise to be skeptical,’’ Edison Investment Research analysts Max Jacobs wrote in a note to investors on Wednesday. “While a takeout could happen for strategic reasons, Biogen offers neither company growth nor synergies, and in the case of Allergan, an acquisition would practically be a merger of equals when taking into account a takeover premium.’’

But others contend Biogen’s recent announcement that longtime chief executive George Scangos will step down in the coming months was read by some in Big Pharma as effectively putting a “For Sale’’ sign on the Cambridge company. Any candidates to succeed Scangos will have to gauge the Biogen board’s thinking on how to approach would-be buyers.

In another investors’ note, Geoffrey Porges, biotech analyst for Leerink Partners in Boston, wrote that “Biogen is the most likely of the large cap biotechs to be sold in the immediate future’’ at a time when the pace of mergers and acquisitions is slowing globally.

“Biogen faces significant strategic challenges,’’ Porges said in an interview. “Its multiple sclerosis business, which makes up the vast majority of its revenue, faces increased competition. But its recurring revenue still makes it attractive to a buyer who could make it even more profitable.’’

The primary draw of Biogen is its experimental neurodegenerative disease therapies that treat unmet medical needs, such as Alzheimer’s and spinal muscular atrophy, Porges said.

“Alzheimer’s is literally the biggest unmet need in our society, and Biogen appears to be making some headway’’ in its drug development, he said. “It’s hard to believe that if this succeeds, it won’t be one of the biggest drugs in the industry. There aren’t many opportunities like that.’’

Not everyone thinks an acquisition of Biogen, the world’s leading maker of multiple sclerosis treatments, would hurt the state’s biopharma cluster. The industry is centered in Cambridge, home to Biogen, Genzyme, and Millennium, which remains chockablock with biotech startups, academic labs, and research centers operated by global drug companies.

“The sector here is mature enough and has gained such a critical mass that I don’t see this [potential takeover] affecting it that much,’’ said Glenn Giovannetti, the Boston-based global biotech sector leader at consulting firm Ernst & Young. “The science will stay here, and those buildings in Kendall Square are still going to be occupied by smart people.’’

But if Biogen is bought, the ranks of independent biotechs with more than one product on the market would further shrink. Merck, one of the companies pursuing Biogen, last year paid $9.5 billion for Lexington antibiotics maker Cubist Pharmaceuticals Inc., the latest in a long string of takeovers of state biotechs dating back to Wyeth Pharmaceuticals Inc.’s buyout of Cambridge-based Genetics Institute Inc. in 2000.

After Biogen, the largest Massachusetts biotech by revenue is Vertex Pharmaceuticals Inc. of Boston, which markets two approved cystic fibrosis drugs. Cambridge’s Alnylam Pharmaceuticals Inc., which ranks third by market value, doesn’t even make the top 10 by revenue. It is working on more than a dozen gene-silencing drugs but has yet to win its first regulatory approval. Dozens of smaller companies with a single approved drug or a pipeline of drug candidates could eventually anchor the next generation of state biotechs, but they’re at least as likely to be acquired.

Back in 2008, when Japan’s Takeda Pharmaceutical Co. bought Millennium for $8.8 billion, it was the biggest takeover ever of a Bay State biotech. That was dwarfed by French drug maker Sanofi SA’s blockbuster $20.1 billion acquisition of Genzyme in 2011.

Takeda and Sanofi have retained their Cambridge operations, continuing to maintain a large research footprint here, though both have cut jobs selectively and dozens of executives have departed — many starting or taking the helm at early-stage biotechs.

Robert Weisman can be reached at robert.weisman@globe.com. Follow him on Twitter @GlobeRobW.