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Tebentafusp-tebn Appproved for Treating Unresectable or Metastatic Uveal Melanoma

Tebentafusp-tebn, a bispecific gp100 peptide-HLA-directed CD3 T cell engager, has been approved for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.

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Efficacy was evaluated in IMCgp100-202 (NCT03070392), a randomized, open-label, multicenter trial of 378 patients with metastatic uveal melanoma. Patients were required to be HLA-A*02:01 genotype-positive identified by a central assay. Patients were excluded if prior systemic therapy or localized liver-directed therapy was administered. Prior surgical resection of oligometastatic disease was permitted. Patients with clinically significant cardiac disease or symptomatic, untreated brain metastases were excluded.


Patients were randomized (2:1) to receive tebentafusp-tebn (N=252) or investigator's choice (N=126) of either pembrolizumab, ipilimumab, or dacarbazine. Tebentafusp-tebn was administered weekly by intravenous infusion at 20 mcg on Day 1, 30 mcg on Day 8, 68 mcg on Day 15, and every subsequent week until disease progression or unacceptable toxicity.


The main efficacy outcome measure was overall survival (OS). An additional efficacy outcome was investigator-assessed progression-free survival (PFS) per RECIST 1.1. Median OS was 21.7 months (95% CI: 18.6, 28.6) for patients treated with tebentafusp-tebn and 16 months (95% CI: 9.7, 18.4) in the investigator's choice arm (HR=0.51, 95% CI: 0.37, 0.71, p<0.0001). PFS was 3.3 months (95% CI: 3, 5) for those receiving tebentafusp-tebn and 2.9 months (95% CI: 2.8, 3) in the investigator's choice arm (HR=0.73, 95% CI: 0.58, 0.94, p=0.0139).


The most common adverse reactions (>=30%) were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common laboratory abnormalities (>=50%) were decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate.


Rare Pediatric Disease Designation for Osteosarcoma Treatment

The FDA has granted Rare Pediatric Disease Designation to clinical-stage drug candidate, CycloSam, for the treatment of osteosarcoma, a devastating form of bone cancer that afflicts mostly children and young adults.


Rare Pediatric Disease Designation, defined as diseases primarily affecting fewer than 200,000 Americans under the age of 18 each year, may provide substantial financial incentives by making companies eligible for a Priority Review Voucher (PRV) upon drug approval by the FDA. A PRV grants accelerated FDA review of a drug candidate for any indication, reducing the review period to 6 months and potentially gaining early market access. PRVs may be used by the recipient company for any drug development program, or alternatively, sold or transferred to larger pharmaceutical companies.


Osteosarcoma is the most common form of bone cancer in children and young adults with primary high-grade bone malignancy. There have been few advancements over the last 40 years for this debilitating and often deadly disease, with treatment often resulting in limb amputation. Accordingly, there is a large unmet market need for a better treatment that is more efficacious against pediatric osteosarcoma and better tolerated by patients.


Development of Non-Addictive Alternatives to Opioids for Acute Pain Management

The FDA has taken new steps aimed at fostering the development of non-addictive alternatives to opioids to manage acute pain and decreasing exposure to opioids and preventing new addiction. The agency issued draft guidance to provide recommendations to companies developing non-opioid analgesics for acute pain lasting up to 30 days, typically in response to some form of tissue injury, such as trauma or surgery. This guidance supports the HHS Overdose Prevention Strategy, which focuses on four priority areas-primary prevention, harm reduction, evidence-based treatment, and recovery support.


"Opioid misuse and abuse remain a serious public health crisis facing the country. Preventing new addiction through fostering the development of novel non-opioid analgesics is an important priority for the FDA," said Patrizia Cavazzoni, MD, Director of the FDA's Center for Drug Evaluation and Research. "The guidance reinforces the agency's commitment to confront opioid misuse, abuse, and addiction by taking steps to help those with acute pain get access to improved non-opioid treatment alternatives."


Prescribed appropriately, opioid analgesics are an important part of acute pain management. However, even at prescribed doses, they pose a risk for addiction, misuse, abuse, or overdose that may result in death. A non-opioid analgesic for acute pain that completely eliminates or significantly reduces the need for an opioid could have a major public health impact by alleviating patient suffering from acute pain while mitigating the risks associated with using an opioid. This guidance may further spur development of these types of non-addictive treatment options to reduce the footprint of opioid use in this setting.


The draft guidance describes the agency's current thinking about three aspects of non-opioid analgesic drug development for acute pain:


* types of drug development programs that may be appropriate to generate data needed to support an indication for the management of acute pain;


* potential use of claims in labeling regarding the elimination or reduction of opioid use and the data needed to support those claims; and


* potential use of the FDA's expedited programs to support the development program.



The guidance also fulfills certain legal requirements of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act, commonly referred to as the SUPPORT Act. It directs the agency to issue or update existing guidance to help address challenges to developing non-addictive medical products to manage pain.


The FDA is accepting public comments on the draft guidance documents until April 11, 2022, so that the agency may consider comments before potentially issuing final guidance documents; however, comments on guidance documents are welcome at any time.