FDA delivered bad news to Novo Nordisk and good news to Celgene in separate decisions Friday on applications for marketing new drugs.

The agency threw a curve to Novo by insisting on another clinical trial assessing the cardiovascular risk of its two new adult diabetes drug candidates, Tresiba® (insulin degludec) and Ryzodeg® (insulin degludec/insulin aspart) in a Complete Response Letter sent to the company on February 8.

FDA’s action came less than a month after the European Commission granted Novo approval across all 27 European Union member states for the drug candidates. Novo has said it expects to launch Tresiba in the U.K. and Denmark during the first half of this year, and in other European markets throughout the rest of 2013 and 2014. Ryzodeg is expected to be launched about one year after Tresiba rings up its first sales.

The FDA decision was surprising since the agency spurned the recommendation of an advisory committee. The Endocrinologic and Metabolic Drugs Advisory Committee in November recommended agency approval of Tresiba after concluding Novo showed sufficient efficacy and safety data to support marketing degludec for use alone or in combination with an insulin boost for blood-sugar control during meals. The recommendation led Novo’s CSO Mads Krogsgaard Thomsen to tell Bloomberg at the time the company was looking to obtain full FDA marketing approval in the first half of this year.

But the panel vote on recommending approval was 8–4. By contrast, the advisory committee came down unanimously on recommending that Novo conduct a trial to examine the heart safety risks of Tresiba.

And worse for Novo, FDA tied any future approval of the drug to the company resolving complaints the agency made in a warning letter Dec. 12, 2012. FDA said Novo failed to prevent microbiological contamination of drug products; and failed to investigate whether a failed batch had been distributed from its manufacturing plant in Novo Alle, Bagsvaerd Denmark, based on a March 12-20, 2012, inspection there by agency inspectors.

In the letter, FDA warned: “Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer.”

Addressing analysts today on a conference call, Novo CEO Lars Rebien Soerensen said: “It’s not a good day for diabetes patients in the U.S., it’s not a good day for Novo Nordisk and for Novo Nordisk shareholders,” according to numerous news reports, adding that the company cannot likely provide the heart safety data this year or in 2014.

Shareholders showed their displeasure through a selloff that lowered Novo’s share price as much as 17% in Monday morning trading.

According to Novo Nordisk, Tresiba has a duration of action beyond 42 hours, making it the first basal insulin to offer patients the possibility of adjusting their time of injection. Ryzodeg can be administered once or twice daily with the main meal(s).

Tresiba and Ryzodeg are two key components in Novo Nordisk’s plans for a beachhead in the long-acting basal insulin segment of the diabetes drug market. The segment is now dominated by Sanofi, whose Lantus (insulin glargine) has grown to a market share estimated at 80% and blockbuster-level annual sales.

Sanofi reported blockbuster results for Lantus last week: Q4 sales of the drug zoomed 22.6% from the final three months of 2011, to about €1.4 billion (nearly $1.8 billion). For all of 2012, sales jumped 19.4% over the previous year, to €4.96 billion ($6.6 billion).

Celgene Wins Pomalyst OK

Celgene said the agency approved the company’s application to market the Pomalyst (pomalidomide) for relapsed and refractory multiple myeloma (MM) patients who did not respond to treatment within 60 days of completion of their last therapy involving two other drugs—one of them the company’s current MM offering. Revlimid (lenalidomide), a derivative of thalidomide introduced in 2004, is approved in combination with dexamethasone for MM patients who received at least one prior therapy, as well as for anemia caused by myelodysplastic syndrome.

Revlimid racked up $1 billion in sales during Q4, 17% above Q4 2011, and nearly $3.8 billion for all of last year, up 17% from 2011.

The second drug failure covered by Pomalyst’s indication is Takeda Pharmaceutical’s Velcade (bortezomib), introduced in 2003 for MM as well as mantle cell lymphoma.

FDA approved Pomalyst following a clinical trial of 221 patients with relapsed or refractory multiple myeloma. The trial was designed to measure the number of patients whose cancer met the objective response rate (ORR) of completely or partially disappearing after treatment. Patients were randomly assigned to receive Pomalyst alone or Pomalyst with low-dose dexamethasone. Results showed 29.2% of patients treated with Pomalyst plus low-dose dexamethasone achieved ORR with a 7.4-month median duration of response. By contrast, 7.4% of patients treated with Pomalyst alone achieved ORR; median duration of response has not yet been reached.

Pomalyst carries a boxed warning advising patients and health care professionals that the drug should not be used in pregnant women because of its potential for causing blood clots, and life-threatening birth defects in their babies.

Because of that risk, Pomalyst will be available only through the restricted distribution program Pomalyst REMS™, short for Risk Evaluation and Mitigation Strategy. Both Revlimid and Velcade are subject to similar REMS programs, which require prescribers and pharmacies to be certified by enrolling and complying with REMS requirements. Female patients with potential for pregnancy must comply with the program’s pregnancy testing and contraception requirements, while males must comply with contraception requirements.

Pomalyst is the second MM drug approved by FDA in the past year. In July, the agency approved Onyx Pharmaceuticals’ Kyprolis (carfilzomib). Both drugs were reviewed through FDA’s accelerated approval program, while Pomalyst was also granted orphan product designation because it is intended to treat a rare disease or condition.

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