Seladelpar

Gilead Sciences, Inc. (GILD) shares gained 15.4% in a year, outperforming the sector but lagging the S&P 500. New drug approvals, pipeline progress, and strong quarterly results boosted investor sentiment. GILD raised its annual guidance, driven by Veklury sales. Its HIV portfolio, led by Biktarvy, continues to grow, with lenacapavir showing 100% efficacy for HIV prevention. Seladelpar's approval for primary biliary cholangitis strengthens GILD's liver disease portfolio. Despite setbacks in oncology, Trodelvy received Breakthrough Therapy Designation for small cell lung cancer. GILD's strong fundamentals and dividend yield make it a good long-term investment.

EMA's CHMP recommended Gilead Sciences' seladelpar for EU approval as a second-line PBC treatment, either with UDCA or alone for non-UDCA responders/intolerants. The European Commission is expected to decide by early 2025. Seladelpar, already U.S.-approved as Livdelzi, targets PPAR-delta to manage liver inflammation and symptoms like itching, based on Phase 3 RESPONSE trial data showing significant improvement in liver damage markers and itch relief. An ongoing Phase 3 AFFIRM trial tests its efficacy in PBC patients with compensated cirrhosis.

Gilead Sciences Inc. received FDA Breakthrough Therapy Designation for Trodelvy in treating extensive-stage small cell lung cancer. Trodelvy, a first-in-class Trop-2-directed antibody-drug conjugate, showed promising antitumor activity in Phase 2 TROPiCS-03 study. Gilead plans a Phase 3 trial for Trodelvy in ES-SCLC patients.

The CHMP of the EMA recommended seladelpar for treating primary biliary cholangitis (PBC) in adults, based on the RESPONSE study showing ALP normalization in 25% of participants and significant pruritus reduction. If approved by the European Commission, seladelpar would offer a new treatment option for PBC in the EU.

FDA identified serious liver injury risk in PBC patients without cirrhosis taking Ocaliva, with higher liver transplant risk compared to placebo. The drug is contraindicated for advanced cirrhosis patients, but some still received it. FDA urges frequent liver tests and discontinuation if signs of progression or lack of efficacy.

November 2024 FDA updates include approval of VARIPULSE for atrial fibrillation, removal proposal for oral phenylephrine in nasal decongestants, CRL for Ocaliva in PBC, acceptance of pz-cel gene therapy BLA for RDEB, approval of Emrosi for rosacea, acceptance of dupilumab sBLA for CSU, CRL for IZERVAY in GA, Gildeuretinol for Stargardt disease receiving Rare Pediatric and Fast Track status, approval of bimekizumab for HS, acceptance of HLX14 biosimilar BLA for denosumab, approval of Attruby for ATTR-CM, and acceptance of vutrisiran sNDA for ATTR-CM.

Approval of ursodeoxycholic acid (UDCA) in 1997 significantly reduced liver transplant and death risks for primary biliary cholangitis (PBC), but up to 40% of patients do not sufficiently respond. Off-label use of fibrates and the 2016 approval of obeticholic acid (Ocaliva) as a second-line treatment provided additional options, though Ocaliva has downsides like increased pruritus. New PPAR agonists, seladelpar and elafibranor, have been approved for PBC, showing potential benefits but with unknown long-term risks.

Advanz Pharma's Ocaliva (obeticholic acid) for PBC loses EU market access as EC revokes conditional marketing authorisation, leaving limited second-line options for patients. Advanz CEO criticizes court's ruling for not assessing patient impact. Ocaliva remains available in the US under accelerated approval.

GSK's phase III GLISTEN study shows linerixibat significantly improves cholestatic pruritus in PBC patients, with potential to be the first global therapy for PBC-related itch. Preliminary safety data aligns with previous studies. Full data to be presented at a future medical conference.

Gilead Sciences announced 81% of PBC participants achieved durable biochemical response by Month 30 with Livdelzi, and 41% normalized ALP levels. Livdelzi also reduced pruritus severity, resolving itch in 27% of participants.