FDA Action Alert: Calliditas, Ionis/AstraZeneca, Amgen and More

FDA_iStock, JHVEPhoto

Pictured: FDA Headquarters in Washington, DC/iStock, JHVEPhoto

The FDA may have moved early on bluebird bio’s Lyfgenia, which was approved two weeks before its originally scheduled review date of Dec. 20, but the agency is still quite active. In the next two weeks, it will release regulatory decisions on investigational treatments for a rare hereditary disorder, non-small cell lung cancer and more. 

Calliditas Strives for Full Tarpeyo Approval in IgAN

On or before Dec. 20, the FDA is expected to release its decision regarding full approval of Calliditas Therapeutics’ Tarpeyo (budesonide) delayed release capsules for the treatment of adults with IgA nephropathy (IgAN) who are at risk of rapid disease progression. Tarpeyo won accelerated approval in this indication in December 2021.

Calliditas is supporting Tarpeyo’s supplemental New Drug Application (sNDA) with data from the Phase III NefIgArd trial, which showed that a once-daily 16-mg dose of the drug induced a statistically significant improvement in estimated glomerular filtration rate (eGFR) over a two-year study period, as compared with placebo.

In the August sNDA acceptance announcement, Calliditas Chief Medical Officer Richard Phillipson said Tarpeyo’s eGFR benefits, combined with its ability to reduce proteinuria, “provide strong rationale for establishing Tarpeyo as the standard of care for IgAN patients.”

Ionis and AstraZeneca Propose Eplontersen for ATTRv-PN

Ionis Pharmaceuticals and AstraZeneca are proposing their investigational antisense therapeutic eplontersen to treat hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). The FDA’s verdict is due on December 22.

Eplontersen’s NDA, accepted in March 2023, is backed by data from the Phase III NERUO-TTRansofrm study, showing that at 35 weeks, patients treated with the antisense therapeutic saw a significant drop in serum transthyretin levels, alongside a significant improvement in neurologic impairment. Eplontersen treatment likewise led to significantly better patient-reported quality of life.

ATTRv-PN is a progressive and debilitating neurological disease characterized by the accumulation of transthyretin across major organs, slowly compromising their function and causing widespread nerve damage throughout the body and ultimately leading to death. Eplontersen works by reducing the production of transthyretin.

Amgen Aims for Full Approval of Lumakras in NSCLC

Amgen’s KRAS G12C inhibitor Lumakras (sotorasib) won the FDA’s accelerated approval in May 2021 for KRASG12C-mutated non-small cell lung cancer (NSCLC). On December 24, the regulator will decide whether or not to grant it full approval.

Amgen’s chances don’t look good, however. This October, the FDA’s Oncologic Drugs Advisory Committee voted 10-2 against full approval of Lumakras in this indication, contending that the data from the confirmatory Phase III CodeBreaK 200 study could not reliably be interpreted.

The FDA’s own reviewers, in a briefing document posted ahead of the adcomm meeting, flagged potential systemic bias in the confirmatory study, including a high rate of study dropouts in the comparator group as well as early crossover into the Lumakras arm.

Merck’s Chronic Cough Drug Again Faces the FDA

After an initial rejection in January 2022, Merck is once again seeking regulatory approval for its chronic cough drug candidate gefapixant. The FDA’s deadline for a decision is December 27.  

As with Amgen, however, the odds don’t seem to be in Merck’s favor. Last month, the FDA’s Pulmonary-Allergy Drugs Advisory Committee overwhelmingly voted against gefapixant’s approval, saying the drug did not provide a clinically meaningful benefit to patients with refractory or unexplained chronic cough.

With a 12-1 split, the panel of external experts agreed with the FDA’s reviewers, who in a briefing document released prior to the adcomm meeting said gefapixant induces only a “small reduction” in cough frequency, and questioned whether the candidate’s efficacy is clinically meaningful.

In a statement following the adcomm, Merck disagreed with the advisers, insisting it has provided strong data to establish gefapixant's efficacy.

FDA to Decide on Zealand’s Congenital Hyperinsulinism Drug

Closing out the year, the FDA will issue a decision regarding Zealand Pharma’s investigational glucagon receptor agonist dasiglucagon for the treatment of pediatric patients aged 7 days and older with congenital hyperinsulinism. The target action date is December 30.

Dasiglucagon is designed as a subcutaneous continuous infusion delivered using a wearable pump system. It works by inducing the liver to release stored sugar into the bloodstream. The FDA first approved dasiglucagon in May 2021 to treat severe hypoglycemia in diabetic patients aged six years and above. For this indication, dasiglucagon is marketed as Zegalogue.

Zealand is supporting dasiglucagon’s most recent NDA with data from two pivotal Phase III trials and interim results from an ongoing extension study. Taken together, Zealand reported that the studies demonstrated that dasiglucagon reduced the need for intravenous glucose infusion, the patients’ time in a state of hypoglycemia and the number of hypoglycemic events compared with standard of care.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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