{"id":5442,"date":"2025-09-26T10:05:53","date_gmt":"2025-09-26T16:05:53","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=5442"},"modified":"2025-09-26T10:15:42","modified_gmt":"2025-09-26T16:15:42","slug":"hansa-where-is-the-beef","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2025\/09\/26\/5442\/hansa-where-is-the-beef\/","title":{"rendered":"HANSA, Where is the Beef?"},"content":{"rendered":"
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\"\"<\/a><\/figure>\n<\/div>\n\n\n

Hansa is a small Swedish company with a unique product, a protease from Strep. pyogenes that cleaves IgG called Imlifidase, Idefirix or IdeS for short. They steered IdeS through a difficult early development, obtained approval for their drug in many EU countries for ‘desensitisation treatment of highly sensitised adult kidney transplant patients with positive crossmatch against an available deceased donor’.<\/p>\n\n\n\n

Most recently the company finished a pivotal Phase 3 trial with what looks at first blush like excellent results. The press release speaks of P-values << 0.05 and of having met primary and secondary efficacy endpoints.[1]<\/a>  What else would one want?<\/p>\n\n\n\n

At the press conference, the analysts \u2013 well behaved as always \u2013 congratulated the company speakers and had some fairly benign questions, questions that anyone working in the field would ask. How about overall mortality?  How about organ survival?  How about safety specifics and the occurrance of AMR? How did the GFR benefit develop over time? <\/p>\n\n\n\n

Strangely, company responses were evasive, suggesting that there was \u2018insufficient time\u2019 to dig deeper into the data. What should have been a glorious and shiny event rolling out impressive results from the best Hansa study ever conducted became an anticlimactic session, with excuses that simply don\u2019t hold water.<\/p>\n\n\n\n

Analysts are a savvy bunch, often PhDs with training in molecular biology.  They come from prestigious universities, understand the science and know what to ask. Most of them are polite enough not to embarrass the corporate speakers by drilling down too deep or challenging their responses.  Trust me, they know when a company side-steps a question or makes thread-thin excuses.<\/p>\n\n\n\n

We are talking, of course, about the Phase 3 InfIdeS study (NCT04935177), a small 64 patient open trial run at top US transplant centers. According to clinicaltrials.gov, it was completed 3 months ago, on 6-20-25 exactly.  By the time of the 9-25-25 teleconference, Hansa had more than enough time to clean and analyze the data. Safety details, number of deaths, the comparative efficacy over time, all this and more must have been known within a week after data lock. Most companies do a good job cleaning data while a study is still running.  In the case of InfIdeS, given its slow enrollment and open design, one would expect minimal work after data lock.<\/p>\n\n\n\n

Knowing this, there is this little cricket chirping in the back of our brain that tells us that something is not quite right here\u2026 and that maybe, just maybe, there is a reason why the company chooses to make excuses, evade answers, and delay a more in-depth data presentation.<\/p>\n\n\n\n

This is unfortunate as IdeS is an amazing drug.  It clearly breaks down IgG, autoantibodies included, in a matter of hours.  Even patients with very high cPRA, ie, those that are very poor candidates for a match otherwise, can be transplanted because IdeS works so fast.  ESRD patients ineligible for transplantation face the prospect of many years on dialysis, often a death sentence.  IdeS is the only drug that can convert a failed cross-match and avoid acute post-transplant rejection safely.<\/p>\n\n\n\n

After transplantation, as the effects of IdeS wear of, IgG levels will return to normal in the organ recipient. The effect of the drug is relatively short, lasting a few weeks, not months. Therefore, it would be unreasonable to expect major long-term benefits beyond the peri-transplant phase except to say that it makes transplantation feasible in the small group of patients who – without IdeS – would have little chance to get a new organ, to come off dialysis, and have a new lease on life.<\/p>\n\n\n\n

Unfortunately, IdeS cannot be dosed repeatedly. As a foreign protein, anti-IdeS antibodies develop quickly and can lead to severe allergic reactions on re-exposure.  It also won\u2019t replace other anti-rejection drugs that are routinely administered post-transplant with good effect.<\/p>\n\n\n\n

As it stands, AMR, albeit rare, is the most important cause of transplant loss nowadays.  There is no data suggesting that IdeS can reduce the occurrance of AMR [2]<\/a> – but Hansa could convince us otherwise by releasing more data.<\/p>\n\n\n\n

In conclusion, we believe IdeS is a very useful drug because of its rapid MoA.  It makes transplantation feasible even in patients at very high-risk of rejection because of their HLA profile and prior sensitization.<\/p>\n\n\n\n

Lastly, a few words about the design of the Phase 3 trial. It seems we are dealing here not just with a 2-arm study as the control group is comprised of 2 very different populations: those that receive a transplant and those who do not. Have a look at the schematic:<\/p>\n\n\n

\n
\"\"<\/a>
Design of Phase 3 ConfIdeS Study<\/figcaption><\/figure>\n<\/div>\n\n\n

<\/p>\n\n\n\n

<\/p>\n\n\n\n

Which comparison gave the P<0.0001 difference quoted in the press release?  One could argue that the proper control group for the IdeS arm would be the group of dialysis patients that cannot be transplanted at all, not the hybrid \u2018control\u2019 depicted in the diagram. Again, it will be important to learn more about the composition of the control group of patients.<\/p>\n\n\n\n

The study also used very strict entry criteria, probably required by Regulators.  By definition, a cPRA score of \u226598% means a patient is highly sensitized.  Major (A, B, C) and minor HLA (DP, DQ, DR) types determine this calculated score.[3]<\/a>  Setting the cPRA threshold at \u226599% certainly made for difficult recruitment but also should have provided a better separation in outcomes.<\/p>\n\n\n\n

Kudos to Hansa for successfully executing a demanding study.  But we still want to see more data and get more answers. Next time with details please!<\/p>\n\n\n\n

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ABBREVIATIONS
<\/strong>AMR\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 antibody-mediated rejection
cPRA\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 calculated panel reactive antibodies
GFR\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Estimated glomerular filtration rate
HLA\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Human Leukocyte Antigen
MoA\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 mode of action<\/p>\n\n\n\n

\n\n\n\n

REFERENCES
<\/strong>[1]<\/a> Conference Call Slide Presentation.  Hansa Biopharma, ConfIdeS US Phase 3 Pivotal Trial, Topline Results, September 25, 2025
[2]<\/a> Jordan S.  Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes).  Transplantation 2021;105: 1808
[3]<\/a> https:\/\/optn.transplant.hrsa.gov\/data\/allocation-calculators\/cpra-calculator\/<\/p>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Hansa is a small Swedish company with a unique product, a protease from Strep. pyogenes that cleaves IgG called Imlifidase, Idefirix or IdeS for short. They steered IdeS through a difficult early development, obtained approval for their drug in many EU countries for ‘desensitisation treatment of highly sensitised adult kidney transplant Continue reading HANSA, Where is the Beef?<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":5452,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,3,18],"tags":[2453,1271,2444,2445,2443,2448,695,2440,2449,1583,2454,2441,2442,2452,2446,2455,1105,2450,1705,2451,2447],"class_list":["post-5442","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","category-the_viewpoint","tag-ada","tag-allphase-pharma-consulting","tag-amr","tag-antibody-mediated-rejection","tag-confides-trial","tag-cpra","tag-dialysis","tag-esrd","tag-hansa-biopharma","tag-harald-reinhart","tag-highly-sensitized","tag-idefirix","tag-ides","tag-igg-protease","tag-igg-reduction","tag-imlifidase","tag-incomplete-data","tag-renal-transplantation","tag-study-design","tag-study-population-selection","tag-x-match"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/09\/Hansa-SLIDER2.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-1pM","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":6682,"url":"https:\/\/allphasepharma.com\/dir\/2026\/03\/22\/6682\/idefirix-pdufa-date-and-the-ides-of-march\/","url_meta":{"origin":5442,"position":0},"title":"Idefirix 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