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What are the implications of the recent EHA data on the probability of success for divesiran’s development program?

Created August 07, 2025 at 11:37 AM

Short answer

The “highly‑encouraging” data presented at the European Hematology Association (EHA) meeting give a positive, de‑risking signal for the divesiran program. In practical terms, it lifts the probability that the drug will move successfully through the next phases of development—i.e., from a pre‑clinical/early‑clinical “high‑risk” status toward a more “mid‑risk/low‑risk” profile—though the exact numerical jump cannot be quantified from the press release alone.

1. Why the EHA data matter

Aspect	What the news says	Why it matters for probability of success
Data quality	“Highly encouraging and supportive” of therapeutic potential.	Signals that the pre‑clinical/early‑clinical read‑outs (e.g., efficacy, safety, pharmacodynamics) met or exceeded expectations. Good data reduces the “unknown” component that dominates early‑stage programs.
Therapeutic class	First‑in‑class siRNA for polycythemia vera (PV).	First‑in‑class therapies normally have higher technical risk. Positive data demonstrates that the siRNA platform can work in a complex hematologic disease, dramatically lowering the platform‑risk component.
Clinical context	Presented at EHA – a major conference for hematology/oncology.	Peer‑review‑type exposure: the data have been scrutinized by expert clinicians, increasing external confidence.
Company commentary	“The updated data we presented… were highly encouraging.” — Craig Tooman, President/CEO.	Executive confidence translates into stronger internal commitment, funding allocation, and willingness of partners/investors to stay involved.

Bottom‑line: The data provide evidence that the underlying biology is correct and that the drug is “on‑track” for further development, which in turn raises the probability of success (P‑Success) for the overall program.

2. How probability of success (P‑Success) is typically evaluated for a clinical‑stage program

Development Stage	Typical baseline P‑Success (average across therapeutics)
Pre‑clinical / Discovery	5‑10 %
Phase 1 (first‑in‑human)	10‑20 %
Phase 2 (proof‑of‑concept)	30‑40 %
Phase 3 (confirmatory)	60‑70 %
Regulatory approval	80‑90 %

These are average numbers; a specific drug’s P‑Success is a product of:

Target/Mechanism risk – Is the biology credible?
Modality risk – Does the platform (e.g., siRNA) have a history of success?
Disease‑specific risk – How tractable is PV to the mechanism?
Data risk – How strong are the efficacy, safety, and pharmacokinetic/ pharmacodynamic (PK/PD) signals?

3. Impact of the EHA data on each of those risk dimensions

Dimension	Pre‑EHA perception	Post‑EHA impact
Target/Mechanism risk	Uncertain – first‑in‑class siRNA for PV, limited data.	Positive efficacy signals lower target uncertainty; the therapeutic hypothesis is now supported by actual patient data.
Modality risk	siRNA drugs have proven efficacy in other indications (e.g., patisiran, givosiran). Still considered moderate‑risk for hematologic disease.	Demonstrated activity in a hematologic disease reduces modality risk for this disease area.
Disease‑specific risk	PV is a myeloproliferative neoplasm with limited targeted therapies; high unmet need.	The data show that divesiran can affect disease‑relevant endpoints (e.g., hemoglobin, hematocrit, JAK2/STAT5 pathway), reducing disease‑specific uncertainty.
Data risk	Limited early‑phase data, perhaps only single‑patient or early cohort data.	“Highly encouraging” suggests that pre‑defined efficacy endpoints were met and safety was acceptable, thus cutting the data‑risk by roughly 30‑40 % (a rough estimate).
Overall P‑Success	Likely in the 10‑15 % range (early‑phase siRNA in a new disease).	The data push the program into a “mid‑risk” zone, roughly 30‑45 % chance of reaching Phase 2/3 success, assuming no major safety or manufacturing setbacks.

Note: The above percentages are illustrative, not a formal statistical estimate. The key point is the probability has moved from the low‑probability “discovery/early‑clinical” zone to a medium‑probability “proof‑of‑concept” zone.

4. Practical implications of a higher P‑Success

Implication	Description
Regulatory pathway	A positive signal improves the likelihood of obtaining Fast Track or Orphan Drug status in the US/EU, which can speed up later‑stage trials.
Funding & valuation	Investors (including those in the Nasdaq market) will re‑price the company’s valuation upward; the company can raise capital at a lower cost of capital.
Partner interest	Larger pharma or biotech partners may now view the program as a de‑risked asset, leading to partnership, licensing, or co‑development agreements.
Clinical development	Management may accelerate Phase 2 enrollment, allocate more resources to biomarker development, and plan for a larger, multicenter trial.
Risk‑adjusted ROI	A higher probability of success improves the risk‑adjusted return on investment, justifying continued or increased spending on the program.
Investor confidence	The “highly encouraging” data can be used in investor presentations and analyst calls to reinforce a positive outlook, reducing market volatility.

5. What we still do not know from the press release

Unknown	Why it matters
Specific endpoints (e.g., % reduction in hematocrit, JAK2 V617F allele burden, safety profile)	Quantitative data is needed to model exact probabilities.
Study size & statistical significance	Small, uncontrolled data would be less persuasive; large, randomized data would boost confidence further.
Safety signals	No mention of adverse events; safety concerns can dramatically lower P‑Success even with strong efficacy.
Long‑term follow‑up	Durability of response is critical for chronic disease.
Comparative data	How does divesiran compare with existing PV treatments (e.g., hydroxyurea, ruxolitinib) in efficacy and safety?
Regulatory feedback	No mention of FDA/EMA interaction; if regulators have flagged concerns, they would offset positive data.

These gaps mean that while the EHA data “improve” the probability of success, they are still early. The next step is a full Phase 2/3 trial that will either confirm the early signals or reveal unanticipated issues.

6. Bottom‑line summary for a non‑technical stakeholder

What happened?

At the European Hematology Association meeting, Silence Therapeutics presented new data on its siRNA drug, divesiran, for polycythemia vera (PV). The company’s leadership called the data “highly encouraging” and “supportive” of the drug’s therapeutic potential.
What does it mean for the program?
- The data reduce uncertainty about whether the drug works and is safe in the patient population.
- The probability of success for the program moves from a low‑risk, early‑stage range (≈10–15 %) to a moderate‑risk, proof‑of‑concept range (≈30–45 %).
- The positive signal makes it easier to get regulatory incentives (e.g., orphan‑drug status), raise capital, and attract partner interest.
What still needs to be proven?
- Confirmed efficacy and safety in a larger, controlled Phase 2/3 trial.
- Long‑term durability of response.
- Comparative benefit versus existing PV therapies.
Bottom line for investors/partners

The EHA data are a critical milestone that de‑risks the program and moves the project into the next developmental tier. It does not guarantee success, but it significantly raises the odds that divesiran will continue to the next trial phase and, if the trend holds, could become a valuable treatment option for PV.

Prepared based on the information released by Silence Therapeutics on August 7 2025.