Solithromycin

December 29, 2016 By Mark Terry , BioSpace.com Breaking News Staff Cempra , headquartered in Chapel Hill, NC, announced today that it had received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) concerning its new drug applications (NDAs) for its antibiotic solithromycin. Solithromycin, both oral and intravenous, was being evaluated for the treatment of community-acquired bacterial pneumonia (CABP) in adults. The FDA indicated it could not approve the NDAs in their current form. The agency also requested more clinical safety data and a resolution to inspection deficiencies found at the company’s manufacturing facility. It did not request more efficacy data. Of particular concern was insufficient characterization of hepatotoxicity. The company stated, “The FDA noted the size of the safety database is limited to 920 patients who received solithromycin at the proposed dose and duration, and is too small to adequately characterize the nature and frequency of serious hepatic adverse effects.” The FDA recommended a comparative study, as well as a study of about 9,000 patients, to exclude serious drug induced liver injury (DILI) at a rate of about 1:3000 with a 95 percent probability. The manufacturing concerns arose during inspections of the Wockhardt Limited and Pfizer ’s Hospira, Inc. manufacturing plants. The company plans to meet with the FDA as soon as possible to discuss the issues, as well as the design of future clinical safety studies. Cempra also will give the FDA an update on manufacturing progress at Uquifia, an alternate GMP manufacturing plant for solithromycin active pharmaceutical ingredient (API). Uquifia is in India-based Vivimed Labs Ltd ’s Spanish business. “As the rates of antibiotic resistance continue to rise, there is an unmet medical need for new antibiotics to treat patients with CABP and Cempra is committed to working with the FDA to achieve the approval of solithromycin as quickly as possible,” said David Zaccardelli , acting chief executive officer of Cempra, in a statement. Cempra plunged at the news, dropping approximately 130 percent to a current value of $2.65. Zaccardelli also stated, “With more than $225 million of cash on hand, patent protection for solithromycin through 2032 and a pipeline that includes fusidic acid and other potential programs for solithromycin, including an ophthalmic formulation, we have flexibility to determine the best course forward for solithromycin and Cempra.” Fusidic acid is Cempra’s second lead product candidate. It has completed enrollment of a Phase III clinical trial in patients with acute bacterial skin infections. It is also evaluating a study of the drug for refractory infections in bones and joints. There is some speculation that Cempra will abandon solithromycin development. At a conference call, Zaccardelli indicated that they wouldn’t know what the cost of a new trial would be until after meetings with the FDA. Andrew Berens , an analyst with Morgan Stanley , predicted in a note to clients that due to the size and cost of the study, as well as the probability of restrictive labeling were the drug to be approved, that the company will likely halt development of solithromycin.

December 6, 2016 By Mark Terry , BioSpace.com Breaking News Staff As the end of the year approaches, there will be many “Best Of…” lists. Brian Orelli , writing for The Motley Fool, takes a little different spin, pointing out a handful of biotech bosses who made the biggest blunders of the year. 1. Prabhavathi Fernandes , Cempra Prabhavathi Fernandes, president and chief executive officer of Cempra . In October, the company announced that the U.S. Food and Drug Administration (FDA) had problems with a manufacturing facility run by Cempra’s contract manufacturing organization (CRO), Wockhardt . As a result of the news, company shares took a dive. Orelli writes, “You could argue that the manufacturing issues were out of the control of the company’s hands, although picking a manufacturer that was following good manufacturing practices certainly would have avoided the issue.” He goes on to point out, however, that it wasn’t the only questionable issue made by Fernandes. Less than a week later, the FDA published details about solithromycin’s potential for liver damage. “Not disclosing the potential liver issues before the FDA briefing documents was a huge mistake,” Orelli writes, “as the 61 percent decline after the FDA disclosure clearly showed. Managing investors’ expectations is one of the top jobs of a CEO.” It may be minor in the long run, however. Yesterday the company announced that Toyama Chemical Company , a subsidiary of FUJIFILM Holdings Corporation , had started Phase III trials of solithromycin in Japan. 2. John Crowley , Amicus Therapeutics John Crowley , chairman and chief executive officer of Amicus Therapeutics . The company’s Galafold (migalastat) to treat Fabry disease, is marketed in Europe, but hasn’t been approved yet in the U.S. Again, this is a case of not managing shareholder expectations. The FDA indicated it wanted more or better kidney biomarker data before U.S. approval. Orelli writes, “When asked about how the discussions with the FDA were going earlier this month, Amicus’ chairman and CEO John Crowley declined to comment, ‘We’ll only confirm that we will provide an update by the end of this quarter.’ Perhaps a better description of how negotiations with the FDA were going would have softened the blow.” On November 28, Amicus provided information on its plans to meet the FDA’s requirements. 3. Matthew Pfeffer , MannKind Matthew Pfeffer , chief executive officer of MannKind . MannKind has been totally beaten up by the failure of its inhaled insulin, Afrezza. MannKind had a marketing deal with Sanofi , but even Sanofi couldn’t make it work, primarily due to how insurers classified the therapy, making it less likely to be chosen for treatment. What Pfeffer did that’s questionable, is after Sanofi abandoned its involvement, Pfeffer decided to try and market the product itself, with little success. “While things could turn around,” Orelli writes, “MannKind would likely have been better off shelving Afrezza and investing whatever it will spend on selling the insulin on developing another drug using its inhaled drug technology.” 4. Hans Bishop , Juno Therapeutics Hans Bishop , president and chief executive officer of Juno Therapeutics . In early July, Juno reported that the FDA had placed a clinical hold on its Phase II trial of JCAR015 in adults with relapsed or refractory B cell acute lymphoblastic leukemia, after two patients died. It was believed that the addition of fludarabine to the pre-conditioning regimen was the cause. The FDA agreed with that reasoning and the trial continued. Then two more patients died of cerebral edemas and the trial was placed on hold again. Fludarabine wasn’t the problem, or wasn’t the only problem. “It’s tough to say Hans Bishop … made a dumb move,” Orelli writes, “since fludarabine seemed like the likely culprit. But assuming the obvious possibility was the case and not investigating further cost the company time and money.” It’s difficult to point the finger and say whether, at the time, any of these seemed like “dumb moves.” It’s always easier to second-guess after the fact. Still, mistakes were made. “The moral of the story here is that investors need to remember that the risk of these CEO decisions are real and set their risk-adjusted valuations accordingly,” writes Orelli.