Grifols doses first patients in Phase 3 SIGMA and XPERT Ig trials
Grifols has dosed the first patients in two separate Phase 3 clinical trials designed to expand the approved US indications for its flagship immunoglobulin (Ig) products, GAMUNEX-C and XEMBIFY. The Barcelona-headquartered plasma-derived medicines group said both studies are intended to offer patients broader treatment options across immune system disorders.
The trials represent Grifols' latest push to extend the commercial reach of its Ig franchise, which the company says continues to grow on the back of rising global patient demand. XEMBIFY, its subcutaneous formulation, saw sales grow by nearly 60% year on year in 2025, according to the release.
The trials
The first study, SIGMA (NCT07582432), is an open-label, multicentre, single-arm prospective trial enrolling 50 participants. It will evaluate the pharmacokinetics, efficacy and safety of GAMUNEX-C given alongside standard medical treatment in patients with secondary immunodeficiency (SID) caused by haematological cancers, specifically chronic lymphocytic leukaemia, multiple myeloma and non-Hodgkin lymphoma, all of which are associated with compromised antibody production. The primary efficacy objective is to demonstrate that serious bacterial infection rates fall below one episode per participant per year. Secondary immunodeficiency differs from the primary humoral immunodeficiency disease for which GAMUNEX-C already holds a US label; a successful outcome here would meaningfully broaden the product's addressable population, which the company estimates at more than one million US patients across the three named cancer types.
The second trial, XPERT (NCT07540221), will assess whether XEMBIFY's pharmacokinetic profile is non-inferior to that of GAMUNEX-C when used as maintenance therapy in approximately 40 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). GAMUNEX-C is already an approved first-line CIDP treatment; XEMBIFY currently holds a US label only for primary humoral immunodeficiency. A positive XPERT readout would support a potential regulatory submission to extend XEMBIFY's label to include CIDP. The study will run across 20 sites in the US and Europe. Around 60,000 people in the US are estimated to be living with CIDP, a progressive autoimmune condition affecting peripheral nerves.
Lisa Butler, president and chief executive of The GBS I CIDP Foundation International, said the foundation "embraces Grifols' commitment to innovate and to support the patient community with additional choice in treatment and access options."
Market context and regulatory read-across
The two new trials join a third Ig study already in progress: the EXCELL trial (NCT05645107), announced in late 2022, which is evaluating XEMBIFY plus standard medical treatment against placebo in patients with hypogammaglobulinaemia associated with CLL, multiple myeloma and NHL. Together the three studies represent a coordinated label-expansion strategy built around the same core Ig franchise rather than a step into new molecular modalities.
The broader Ig market is competitive and supply-constrained. Grifols competes principally with CSL Behring's Privigen and Hizentra, Octapharma's Octagam, and Takeda's Hyqvia and Gammagard in the IVIg and SCIg segments. Subcutaneous formulations have gained traction with both prescribers and patients because home administration removes the need for clinic-based infusions, which partly explains XEMBIFY's growth trajectory. US label expansion into CIDP would put XEMBIFY in more direct competition with CSL Behring's Hizentra, which already holds a CIDP indication following the PATH trial, and with Takeda's Hyqvia. Regulatory precedent for SCIg in CIDP therefore exists, giving Grifols a clearer pathway to approval if XPERT demonstrates non-inferiority on pharmacokinetic endpoints.
Grifols is listed on both the Spanish IBEX-35 and NASDAQ, and the Ig franchise is central to its revenue base. Investors will be watching enrolment pace and interim pharmacokinetic data from both trials as near-term catalysts, with full readouts likely several years away given Phase 3 timelines.