In its last meeting of the year, the FDA’s Oncology Drugs Advisory Committee (ODAC) is scheduled for a triple-header this week. The action begins Tuesday with consideration of a supplemental new drug application (sNDA) for Astrazeneca plc’s Lynparza (olaparib) tablets as a maintenance treatment for adults with metastatic pancreatic ductal adenocarcinoma who have germline BRCA-mutations (gBRCAm) and whose disease has not progressed on first-line platinum-based chemotherapy. In its briefing document for the meeting, the FDA expressed concern about potential uncertainties in the POLO trial, which compared the efficacy and safety of Lynparza with placebo. Given the small size of the trial, the FDA is questioning whether it was adequately controlled and whether the impact of imputation in patients who are missing data is larger in a smaller trial. If it gets the FDA’s green light, the PARP inhibitor would be the first therapy specifically approved for the indication. Lynparza already has been approved to treat patients with gBRCAm advanced ovarian cancer. Later Tuesday, ODAC will discuss a supplemental biologics license application for Merck & Co. Inc.’s Keytruda (pembrolizumab) as a treatment for patients with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk, non-muscle-invasive bladder cancer (NMIBC). In a single-arm trial, 40 of the 102 patients treated with Keytruda had a complete response (CR) at month 3. The median duration of the response was 16.2 months, and as of Sept. 24, 19 patients had remained in response for at least one year. “While FDA guidance states that CR rate and duration of response in a single-arm trial are appropriate efficacy endpoints to evaluate a treatment for BCG-unresponsive NMIBC for approval, an advisory committee has not previously discussed what magnitudes of these endpoints may be considered clinically meaningful,” the agency said in its briefing document. In its final action for the year, ODAC will have a half-day session Wednesday to weigh in on Epizyme Inc.’s NDA for tazemetostat tablets as a treatment for patients with metastatic or locally advanced epithelioid sarcoma (ES). The FDA’s briefing document for the session seems “a bit harsh given the relatively low response rate of 11-15% in a single-arm open-label study, which historically (and in our experience) is a tough call for approval,” Jefferies analyst Michael Yee said. While he sees only a 20% to 25% probability of tazemetostat getting a positive vote from ODAC, Yee said that doesn’t change his thesis of “significant upside potential” from a potential approval of the drug in follicular lymphoma (FL), which is a $500 million-plus market versus less than $50 million for the sarcoma indication. “ES was merely the lead indication to get the drug out in the market early, but the bigger and more important population of FL is pretty close behind” Yee said. Epizyme is submitting an NDA this month for the lymphoma indication, for which it shows a better benefit/risk profile, he added.

The U.S. Court of Appeals for the Federal Circuit Monday left standing a 2017 jury decision that Hospira Inc., part of New York-based Pfizer Inc., must pay Amgen Inc. a $70 million lump sum for infringing its ’298 patent, which relates to erythropoietin (EPO) isoforms and aspects of their production. Aside from the validity of the patent, which the jury upheld, at issue in Hospira Inc. v. Amgen Inc. was whether 21 batches of EPO that Hospira manufactured in 2013, 2014 and 2015 were outside the safe harbor granted for biosimilar development. Hospira suggested “that the safe harbor exemption always applies in the pre-approval context,” according to the court, which reiterated that it has rejected that assumption in the past. The jury also rejected that argument when it found seven batches were protected under the safe harbor, but 14 were not because they weren’t manufactured “solely for uses reasonably related to the development and submission of information” to the FDA, according to the court. Although not required by the FDA, Hospira used the 14 batches for revisions to release specifications, stability testing, continued process verification (CPV) and various types of testing, including biosimilarity. The Federal Circuit cited documentary evidence showing “that Hospira planned for ‘the balance of the material from the 2013 campaign (approximately 50%) and most of the material from the 2014 and 2015 campaigns [to] serve as commercial inventory to support single dose vial launch stock.’” Initially, Hospira was planning a biosimilar launch date in 2015, before the expiration of the ’298 patent. But those plans met regulatory delays, including a complete response letter, with Hospira’s biosimilar Retacrit not being approved until May 2018. The court observed that when Hospira resubmitted its biosimilar application in late 2015, after litigation began, the company changed the designation of certain batches from “commercial inventory” to “CPV,” which Amgen’s expert witnesses testified is an ongoing process that applies to batches made for commercial use, not development. The court further noted that “simply submitting information about a drug substance lot to the FDA” does not place the manufacture of that lot within the safe harbor. Also, “routine record retention requirements associated with testing and other aspects of the commercial production process” are not protected by the harbor, the court said. In addition, the Federal Circuit found the $70 million award reasonable as it fell between the amounts proposed by each side. Amgen, of Thousand Oaks, Calif., had proposed an award of $154 million to $170 million, and Hospira had suggested $4.1 million to $4.6 million per batch, which would have added up to more than $64 million for the 14 batches. In ruling against Hospira’s appeal, the Federal Circuit also denied Amgen’s appeal of the jury’s finding that, while a second patent was valid, it was not infringed by Hospira. The ’349 patent claims vertebrate cells that can be propagated in vitro and are capable of producing specific levels of EPO in 48 hours as determined by radioimmunoassay.

The SEC’s Small Business Capital Formation Advisory Committee is recommending several ways to make crowdfunding a more viable option for small businesses to raise capital. One recommendation is to raise the $1.07 million per year offering cap, which could make the pathway more appealing to small biotechs. Other recommendations include removing limits on accredited investors’ investment amount, changing investment limits to apply on a per investment basis rather than using annual investment limits, allowing eligible investors to invest through special purpose vehicles and allowing greater flexibility in portal compensation.

The FDA issued two draft guidances last week to aid in drug development. One discusses the qualification process for drug development tools (DDTs) for a specific use, as defined in the 21st Century Cures Act. A voluntary process, qualification permits use of a DDT, within the boundaries justified by data, across multiple drug development programs. The guidance is intended to help sponsors better understand the regulatory qualification process for DDTs, which are intended to accelerate the integration of innovation, clinical knowledge and scientific advances into drug development while providing opportunities to better target and expedite individual drug development programs. The second draft would implement changes the FDA Reauthorization Act made to requirements for pediatric studies of certain oncology drugs. The guidance addresses early planning for the pediatric evaluation of molecularly-targeted oncology drugs for which original NDAs and BLAs are expected to be submitted to the FDA on or after Aug. 18, 2020. If an original NDA or BLA is for a new active ingredient and the drug is intended to treat an adult cancer and is directed at a molecular target the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer, reports on the required molecularly-targeted pediatric cancer investigation must be submitted with the marketing application, unless that requirement is waived or deferred, according to the FDA. The guidance describes the agency’s relevant and nonrelevant molecular target lists that are intended to serve as a guide to sponsors as they consider development plans for new targeted drugs and the need for early pediatric assessments. Comments on both draft guidances are due by Feb. 12.

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