Genzyme Corp. hosted its second investor meeting in two months Dec. 20, this time to lay out the basis for its bullish peak sales estimates for alemtuzumab in multiple sclerosis ($3 billion to $3.5 billion by 2017).

The quick reunion is part of a campaign to convince investors to hold out for a higher offer from hostile bidder Sanofi-Aventis SA. But most of the information presented - from Phase II safety and efficacy data to an independent third-party marketing analysis - was old news and the meeting did little to sway investors, with the stock trading down below $70 Dec. 20, closer to Sanofi's $69-per-share bid. It rebounded some the next day to close Dec. 21 at around $71.

Genzyme's five-year MS sales targets for alemtuzumab are unquestionably ambitious, particularly since Phase III data are not yet available. What's more, the MS drug market could see multiple new entrants by the time Genzyme launches its compound (expected in 2012).

Complicating further alemtuzumab's path to success, the first generic version of the current MS market leader, Teva Pharmaceutical Industries Ltd.'s Copaxone (glatiramer), may emerge during that same timeframe. Among the new drugs that may be vying for market share are three oral contenders: Novartis AG's Gilenya (fingolimod), which already launched in the U.S. in October, Merck KGaA's cladribine, under review in the U.S., and Teva's laquinimod, which just completed Phase III.

Forecasts for alemtuzumab hinge on the drug achieving a 5% market share the first year, then 10% to 12% in years two and three before reaching a peak market share of between 18% to 20% in year five, the company reported.

This complex market and Genzyme's bullish forecast, combined with the constrained launch environment for new drugs generally, make it unlikely that Sanofi will significantly increase its offer (the company had no comment to add) The French drug maker extended its original $69-per-share offer to Jan. 21 after the Dec. 10 deadline expired with hardly any Genzyme shareholders tendering their shares (Also see "Sanofi Extends $69-Per-Share Tender Offer For Genzyme To Jan. 21" - Pink Sheet, 13 December, 2010.).

Recent leaks have suggested the sides potentially could hammer out a deal by negotiating around a contingent value right linked to alemtuzumab in which Sanofi would dole out future payments tied to the success of the drug in MS, although Genzyme also wants to see the upfront offer increased.

Sanofi, however, has made it no secret that it thinks Genzyme's sales forecasts for alemtuzumab are outlandish, and has put the peak sales value at just $700 million. Analyst forecasts generally fall somewhere in the middle. ISI Group analyst Mark Schoenebaum forecasts peak sales of $2.3 billion.

How Genzyme Sees Alemtuzumab Stacking Up To Rivals

Perhaps the more interesting takeaways from the Genzyme analyst meeting, given the competitive marketing dynamics in MS, were the biotech's perspective on where it sees alemtuzumab fitting into the treatment paradigm for MS, how it potentially could be priced compared to competitors, and what the company is doing to make the case for reimbursement to payers.

The company announced it will sell the drug under the brand name Lemtrada. It is already available as Campath for B-cell chronic lymphoctyic leukemia, an indication for which it is expected to generate $150 million in sales in 2010. Unlike the influx of new oral MS treatments, Lemtrada is an infusion, but one that would be given annually, starting with an initial five-day infusion the first year followed by three infusions 12 months later. Elan/Biogen Idec's current MS treatment, Tysabri (natalizumab), against which Lemtrada would compete in the second-line, is infused monthly.

"We expect that the advantage of annual infusions might provide us also a leg up in contrast to daily oral therapy, where you're contrasting essentially over a two-year period of time, eight infusions versus well over 700 pills a patient," said Mark Enyedy, president, genetics, transplant, oncology and multiple sclerosis.

In Phase II clinical trials, alemtuzumab was shown to have an impressive efficacy profile versus Merck KGaA's interferon Rebif (interferon beta-1a). Interviews with more than 2,500 prescribers show that based on the Phase II data results, physicians view alemtuzumab as having best-in-class efficacy, Genzyme claims. Nonetheless, its safety profile is not without concerns, and on questions of safety, alemtuzumab falls well below Copaxone and the interferons in physician perceptions. In clinical studies, the drug was associated with immune thrombocytopenic purpura, hyperthyroidism and hypothyroidism, and thus, it will require an extensive safety monitoring program, according to Genzyme.

Genzyme expects Copaxone and the interferons will be used most frequently in the treatment-naive setting followed by Gilenya and other oral entrants, but in the second line for relapsing patients, alemtuzumab will be prescribed most frequently, ahead of Tysabri and the oral drugs, the firm predicted. Tysabri will be relegated mainly to the third line, the firm said.

The company is looking to build a pharmaco-economic case as well that positions alemtuzumab as the most cost-effective therapy on the market, based on the unique two-time dosing scheduling and efficacy data resulting in fewer hospitalizations and improvements in physical ability. Discussions with payers in Europe suggest they would be willing to pay a premium over Tysabri if the efficacy and safety profile hold up in Phase III studies, Genzyme said.

The company declined to comment on pricing specifically, but the fact that alemtuzumab is already available for cancer is a complicating factor. Because it is administered at a much higher dose and more often in cancer, Genzyme has to find a way to raise the price for MS without impacting the cancer indication. Managing different pricing scenarios for different indications be challenging.

"We are concerned about managing the use of the oncology product in MS," Enyedy acknowledged. However, he said, "There are a range of solutions there." One scenario that has been floated in media reports is the possibility of giving Campath away for free under a compassionate use program, although how seriously Genzyme is weighing that scenario is unclear.

-Jessica Merrill (j.merrill@elsevier.com)

Where Does Genzyme See Alemtuzumab For MS? After Gilenya, Before Tysabri

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